AODIALOGUE

AO Foundation

The magazine for the AO community 1 / 07

Community zone

AO—strengthening our brand for the futureNew corporate identity released April 2007

Expert zone

Implant surfaces: Do they have any relevance to the surgeon?Research within AO

2 AODIALOGUE 1 | 07

Table of contents

community zone

AO in depth

4 AO—strengthening our brand for the future

people

6 Sigmund Freud—his oral neoplastic disease and oral, maxillary, and facial surgery 10 Sylwester Gogolewski

events

11 AO in Scotland12 Davos Courses 2006—assessment and evaluation15 AO Educators’ Seminar for ORP, Davos 2006—a week to remember

news

18 AO Principles of Fracture Management19 AOSpine Manual

expert zone

20 Implant surfaces: Do they have any relevance to the surgeon?

25 Platelet-rich plasma for bone healing—to use or not to use?

30 Biotechnology in musculoskeletal surgery: outlook and expectations

36 Pelvic and acetabular fractures—past, present, and future

40 AO Debate—acute on chronic, unstable slipped capital femoral epiphysis

AO Dialogue May 2007 Editor-in-Chief: James F KellamEditorial Advisory Board:Jorge E AlonsoJames HunterFrankie LeungJoachim PreinJaime QuinteroPol M RommensPublisher: AO FoundationDesign and typesetting: nougat.chPrinted by Bruhin Druck AG, Switzerland

Editorial contact address: AO FoundationStettbachstrasse 6CH-8600 DübendorfPhone: +41(0)44 200 24 80Fax: +41(0)44 200 24 60E-mail: dialogue@aofoundation.orgCopyright © 2007AO Foundation, Switzerland

All rights reserved. Any reproduction, whole or in part, without the publisher’s written consent is prohibited. Great care has been taken to maintain the accuracy of the information contained in this publication. However, the publisher, and/or the distributor and/or the editors, and/or the authors cannot be held responsible for errors or any consequences arising from the use of the infor-mation contained in this publication. Some of the prod-ucts, names, instruments, treatments, logos, designs, etc. referred to in this publication are also protected by patents and trademarks or by other intellectual property protection laws (eg, “AO”, “TRIANGLE/GLOBE Logo” are registered trademarks) even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name, instrument, etc. without designa-tion as proprietary is not to be construed as a representa-tion by the publisher that is in the public domain.

Research within AO.

Read more in the expert zone.

AODIALOGUE

3

the AO Foundation. Without a policy or

program in communications, we lack

the ability to meet the needs of our in-

dividuals and stakeholders who are in-

volved with the Foundation, which is

you, our readers and you, our course

participants. We also lack the ability to

promote ourselves throughout the world

as an independent academic surgical re-

search and education foundation. Mr

Daemon has an impressive background

in communication and most important-

ly has a philosophy of communication

that matches the vision and mission of

the Foundation. As Editor of AO Dia-

logue and the head of the AO Commu-

nications Advisory Board, I wish to wel-

come him aboard and look forward to

the changes he will bring us.

Finally, in the expert zone there are sev-

eral articles by our research scientists.

These individuals, Mauro Alini, Geoff

Richards, and one of our biotechnol-

ogy advisors from the AO Biotechnol-

ogy Advisory Board, David Grainger,

are bringing forth changes in how we

approach fracture fixation and fracture

healing. Mauro Alini reviews platelet

derived growth factors and their effect

on bone healing. Geoff Richards shows

how changes in implant surfaces can

modify how the body reacts to the im-

plant. David Grainger provides an over-

view of the change that biomaterials

and biotechnology may have in our fu-

ture care of musculoskeletal injury and

disease.

Once again, although change strikes

fear and concern in our hearts, if done

well and for the appropriate reasons, it

can only make us better as it can for the

Foundation.

James F KellamEditor-in-Chief

james.kellam@aofoundation.org

editorial

Changes

We ask why someone has done this to

us. Life was satisfactory so why are you

doing this to me? However, we must

recognize that at times change is for the

better and necessary. This issue of the

AO Dialogue brings to our readers sev-

eral major advantageous changes with-

in the Foundation.

Firstly, the AO image is in the process of

change. All of you are very familiar with

the Blue Triangle and Yellow World that

form our logo. This logo has important

traditional and personal connections

to AO and to Davos so to change it has

many very important considerations for

the AO Foundation. Consequently it was

decided not to get rid of it completely but

to standardize it so that it will be recog-

nized worldwide and used in a standard

fashion. Our President, Christian Van

der Werken will outline the reasons for

this change and the importance of this

change for the AO Foundation.

Secondly, I would like to introduce you

to Herwig Daemon, our new head of

communications. Communications is

a new but very important area within

The mention of change always throws fear into most of our hearts. What we were comfortable with is about to be changed.

4 AODIALOGUE 1 | 07

• To modernize the overall AO brand commu-

nications appearance. In doing so, we portray

ourselves as a modern organization by slight-

ly updating the earlier designs. The AO logo

will be modified, with different logo versions

for different applications to accommodate a

variety of print technologies (Fig 1). We will

maintain our existing typography (Formata

and Meridien fonts) for familiarity. Our brand

colors of blue and yellow will be redefined to

strengthen the print quality, and we will use

secondary colors for charts, graphics, and a re-

definition of imagery and style (Fig 2).

• To simplify the complex AO brand structure

that currently exists. Today each institute,

region, and section has its own brand design.

(see Fig 3) As a single organization, we can

consolidate each of those institutes, regions

and sections to be recognized as “one AO”.

By simplifying our brand structure, we will

achieve one streamlined look for all organi-

zational units within AO and increase brand

recognition worldwide.

Put simply, Corporate Identity is the identity of

a corporation or organization which appears in

the form of a brand, trademark or logo—usually

created within a set of guidelines. These guide-

lines are crucial because they define how the

identity is applied for consistent use: through

colors, typefaces, layouts, logical “brand” hierar-

chy, and so on.

Strengthen, modernize, simplify, reduceThe efforts to create an updated, consistent Cor-

porate Identity for the AO are based on four main

goals:

• To strengthen the AO brand recognition as

well as our worldwide recognition. This is pos-

sibly the biggest challenge we face today. With

the impact of globalization, it is more crucial

than ever to present one face to the world. An

easily distinguishable identity also appeals

more to its target audience. The AO name and

logo are strong, and have been around long

enough to prove so. But an attractive logo is

not enough—for a brand to achieve recogni-

tion, it requires consistency in its use. And

that can only happen through having a clear

set of guidelines, and adhering to them.

Christian van der WerkenPresident of theAO Foundation

chris.vanderwerken@aofoundation.org

A Message from the President

AO—strengthening our brand for the future

At the start of April 2007, AO released its new Corporate Identity to the world. But what exactly is Corporate Identity, and why is it important?

5community zone AO in depth

• To reduce costs. A new “one-size-fits-all” con-

cept will involve a consolidation of formats,

including the development of a web-based

design tool for non-design professionals that

is easy to use. Our existing media will be re-

developed, with new stationery (DIN and US

formats), newsletters, notepads/forms, litera-

ture (brochures—from the annual report to

the course programs), presentations, posters,

and any other special formats.

Roll-out planEach AO employee involved in planning, creat-

ing, or implementing media will receive a set of

guidelines in the near future. I’m looking for-

ward to seeing the effects of this new initiative,

and am counting on each and every AO employ-

ee to help ensure that these guidelines will be

consistently carried out in order to make it a real

success.

For addtional information go to:www.aofoundation.org

Pantone© 294 C

CMYK 100/68/7/30

Pantone© 109 C

CMYK 0/10/100/0

Colors

Fig 1 The modifi ed AO logo.

Fig 2 The AO brand colors.

AO Foundation AO East Asia AO Austria

AO CMF

AO Alumni Association

AO Foundation Research

AO Latin America

AO Switzerland

AO Veterinary

AO ORP Alumni Association

AO Foundation Development

AO North America

AO Germany

AO Foundation TK System

AO Spain

AO Foundation Clinical Investigation

AO UK

AO Foundation Education

AO Foundation Publishing

AO Foundation Research Fund

Organization Regions Sections Specialties Alumni Associations

AO Alumni AssociationChapter Germany

AO Alumni AssociationChapter France

AO Alumni AssociationChapter USA

AO Alumni AssociationChapter Czech Republic

AO Alumni AssociationChapter Thailand

and more

Sender address structure

Fig 3 The modifi ed AO address “tree“.

6 AODIALOGUE 1 | 07

Sigmund Freud (1856–1939), the

founder of psychoanalysis, devel-

oped a carcinoma of the buccal cav-

ity in 1923, which was treated be-

tween 1924 and 1938 by Prof Hans

Pichler (1877–1950), Professor of

Oral, Maxillary, and Facial Surgery

at the University of Vienna, Aus-

tria. Freud and Pichler were both

professors there.

Freud’s neoplastic disease illus-

trates the development of onco-

logical oral, maxillary, and facial

surgery from 1920–1940, and the

problems of maxillary resection. It

also shows the specialty’s medical

and technical developments which

occurred in that time period.

This chronicle takes place against

the backdrop of the National So-

cialist dictatorship in Germany and

Austria.

Detailed information on Freud’s neo-

plastic disease is available from two

sources. The first is Pichler’s 80-page

closely-written case history report,

and the second is Freud’s 1929–1939

diary, in which he recorded percep-

tions about his own health.

The first consultation with Pichler

in 1919 was occasioned by painful

Prof Nicolas HardtClinic for Oral, Maxillary and Facial Surgery, Cantonal Hospital, Lucerne, Switzerland

nicolas.hardt@ksl.ch

swelling in the area of the right pal-

ate and maxillary tuberosity which

had lasted for about a week.

In 1920, an ulcer developed in the

same area of the tuberosity, which

healed by itself.

Despite being forbidden to smoke,

Freud continued to smoke 20 cigars

daily. In February 1923, the re-

newed occurrence of erosion in the

area of the right posterior alveolar

tuberosity was diagnosed by his

treating internist Dr Felix Deutsch

as leucoplakia with dysplasia. He

was referred to Prof Markus Hayek

(1861–1941), Head of the Ear, Nose,

and Throat clinic in Vienna.

Prof Hajek undertook a partial local

excision in the area of the right

tuberosity under local anesthesia.

Postoperation, significant arterial

bleeding was stemmed by the at-

tending nurse.

The histopathological examination

showed the presence of a squamous

cell carcinoma. Freud was not in-

formed of this, and he was referred

to Prof Guido Holzknecht (1872–

1931), who applied radiotherapy.

In September 1923, during a jour-

ney to Rome, Italy, Freud suffered

Sigmund Freud

His oral neoplastic disease

and oral, maxillary,

and facial surgery

1 Sigmund Freud at different times in his life.

1909 1923 1930

1931 1935 1938 1939

1914

7community zone people

tions between 1926 and 1928, each

comprising local excisions and dia-

thermy treatment. In March 1928,

a fifth new obturator prosthesis was

inserted.

By 1929 Freud had lost confidence

in Dr Deutsch, and Dr Max Schur

(1897–1969) took over the follow-

up visits as his personal physician–

a total of 49 consultations. Pichler

performed no new treatments from

June 1928 to 1929.

In 1929, political unrest first be-

came apparent with the raids of

Nazi groups on Prof Tandler’s Ana-

tomical Institute, forcing students

to flee through windows.

In the fall of 1929, Freud traveled

to Berlin for the new construction

of obturator prostheses by Prof Her-

mann Schröder—an oral surgeon

at the Charité University Hospital.

In October 1930 there was a clear

recurrence at the operation site,

leading to an eleventh operation by

Pichler with further resection, split

skin transplantation from the fore-

arm, and a renewed intraoperative

insertion of an obturator prosthe-

sis. The histopathological findings

showed precancerous changes.

More relapses occurred in February

and April 1931. These relapses were

treated by means of electrocoagu-

lation, which had been introduced

into surgery in 1930 by Hans von

Seemen, a pupil of Erich Lexer.

The recurrence in April 1931 was

excised during an additional sur-

gical intervention under local an-

esthesia. This resulted in major

arterial bleeding, and the resected

area was covered with a split skin

graft. The histopathological results

from a major oral hemorrhage,

which stopped without treatment.

Once home, he consulted Pichler,

who recorded the findings shown

in figure 3. Tumor growth was con-

firmed in the area of the tuberosity,

palatoglossal arch, and palate, with

involvement of the cheek and man-

dible.

On October 4, 1923, assisted by

Bleichsteiner, Pichler performed

a ligation of the right external ca-

rotid artery, with extirpation of the

submandibular and cervical lymph

nodes.

In a follow-up operation one week

later, a partial maxillary resection

was performed. Covering of the

wound surfaces was carried out

using the split skin graft technique

published in 1917 by Esser (1877–

1976), and by the insertion of a pro-

visional obturator prosthesis. On

the evening of the operation, Freud

enjoyed two Havana cigars.

Based on the histopathological re-

sults (R1 resection), Pichler, as-

sisted by Hofer and Bleichsteiner,

performed a fourth operation on

November 12, 1923, which com-

prised further resection of the pter-

ygoid process and a partial resec-

tion of the soft palate.

During 1923 and 1924, there were

a total of 143 outpatient consulta-

tions with Pichler. Three new obtu-

rator prostheses were made in this

time period.

Between 1926 and 1936 there was

a cycle of continually relapsing leu-

coplakia, nonspecific proliferations,

precancerous changes, and papillo-

mas. This led to 122 consultations

and 5 further operative interven-

again showed

the presence of

a precancerous

lesion.

Freud turned

to Prof V Kan-

zanjian (1879–

1974) to con-

struct three

new prostheses

in Hans Pichler’s laboratory. One

was made of hard rubber, and two

from hard rubber with a palate sec-

tion made of soft rubber. The cost

of these prostheses was US $6,000,

and paid for Boston based Kanzan-

jian‘s European vacation.

Freud’s acceptance of prostheses

was extremely bad, he called them,

“the curse of my life”.

In 1932, four operations with exci-

sions and electrocoagulations were

performed for multiple recurrenc-

es. The histopathological diagnosis

of cancer in situ continued to be

made.

When the Nazis took power on Jan-

uary 30, 1933, Germany not only

experienced political changes, but

also a power takeover of its clin-

ics. Under an April 1933 law, po-

litically unreliable professors were

dismissed from public office (a total

of about 15%, up to 30% in Berlin

and Frankfurt). Racism played a

decisive role in only a third of the

professors dismissed (Evans 2000).

This affected 11.5% of all internists,

10% of surgeons, 17% of neurolo-

gists, 90% of psychoanalysts and

5% of oral surgeons. At the Charité

in Berlin, every third doctor was dis-

missed (Bleker and Jachertz 1989).

Prof Cohn-Stock (1891–1985), who

2 3 4 5

2 Prof Markus Hajek (1861–1941).3 Findings at the consultation with Prof

Pichler in 1923.4 Prof Hans Pichler, 1923.5 Dr Max Schur (1897–1969).

Freud’s acceptance of prostheses was extremely bad, he called them, “the curse of my life”.

8 AODIALOGUE 1 | 07

movement, as the Austrians will

not become as brutal as the Ger-

mans”.

A classical failure of judgment, as

resulting events would show.

June 6, 1933: “The world is a huge

prison and Germany is the worst

cell. It pleases me to think that we

are still living as if on an island of

the blessed”.

Freud must have known that the

elite of German psychiatry pas-

sionately supported the Nazis’ laws.

For example, the neurologist and

psychiatrist Prof Carl Bonhoeffer,

while explicitly against killing by

doctors, nevertheless did not con-

demn the inhuman practice of ster-

ilization (Kater 2002).

In 1934, on the recommendation of

Prof Rigeaud of the Institut Curie

(Paris) and Prof Schloss (Vienna),

a radium prosthesis was inserted.

No further details exist. Further re-

lapses occurred, resulting in three

local operative interventions in

May, June, and September 1934.

The first signs of political chaos in

Austria began with the murder of

the Federal Chancellor, Dollfus, by

Austrian Nazis on July 25, 1934.

Freud’s health continued to suffer.

In 1935 four operations were per-

formed with the diagnoses: verru-

cous leucoplakia, papilloma, and

precancerous papilloma.

In January and March of 1936, the

26th and 27th operations were per-

formed, with the same histopatho-

logical findings of verrucous leuco-

plakia. In July the 28th operation,

the first to be performed not under

local anesthesia, but using nitrous

performed the first maxillary seg-

ment osteotomy in 1920, was one of

many who then emigrated.

At the notorious book burning at

the University of Berlin on May 10,

1933, Freud was declaimed with

the sentence: “against the overesti-

mation of life’s psychological drives

which eat away at the soul, and for

the nobility of the human spirit. We

surrender the written works of the

Jew S Freud…”

Compared to the lot of German

Jews, Freud considered life in Aus-

tria to be like living on an island

of the “blessed”. He was under the

false impression that anti-Semitism

would not find fertile soil in Aus-

tria.

Freud in January 1933: “People are

afraid that the German nationalis-

tic excesses are going to encroach

on our little

country. That

is nonsense. I

do not see any

danger here”.

April 8, 1933: “If

the Nazi move-

ment extends

to Austria, its

course will not

be marked by

the excesses of

the German

oxide anesthesia and local anesthe-

sia, with the resection of an ulcer in

the area of the palate took place.

The histopathological diagnosis

showed the presence of a squamous

cell carcinoma, 13 years after the

first diagnosis. As there were no

tumor-free areas in the contours, a

29th operation was performed with

follow-up resection, and again in

December, another operation under

nitrous oxide anesthesia, with co-

agulation of a new ulcer.

An extreme trismus followed, for

which newly discovered short wave

treatment was applied.

The 31st operation was performed

in April 1937, and no new tumor

growth was found. The extreme

trismus and pain remained; the

maximal mouth opening was mea-

sured as 12mm distance between

incisor teeth.

The pathologist Prof Erdheim, who

had provided almost all the previ-

ous histological diagnoses, died at

the end of 1937. So great was his in-

volvement in this case that he was

able to identify unlabeled sections

as belonging to Freud.

In January 1938, a squamous cell

carcinoma again recurred in the

areas of the maxillary antrum and

orbital floor, leading to a 32nd op-

eration under nitrous oxide anes-

thesia with extensive resection of

these regions.

A follow-up resection performed in

February showed only leucoplakia.

In March 1938, the Nazis assumed

control of Austria. Freud described

this as FINIS AUSTRIAE, by which

he was referring more to the demise

116 7 8 9

6 Prof Hermann Schröder of the Berlin Charité.

7 Prof Jakob Erdheim (1874–1937).

8 Prof V Kanzanjian (1879–1974).

9 Obturator prosthesis with detachable palate section.

10 Prof Günther Cohn-Stock (1891–1985) Charité Berlin.

11 May 10, 1933: Burning of books.

10

“People are afraid

that the German

nationalistic excesses

are going to encroach

on our little country.

That is nonsense.

I do not see any

danger here.”

9community zone people

During an examination in London

in July 1938, Dr Exner, a South Af-

rican oral surgeon who had previ-

ously been a guest of Pichler, could

also find no tumor; although Schur

was convinced that a recurrence of

the tumor would occur.

Pichler flew to London on Septem-

ber 7, 1938, and his examination

showed an extensive recurrence of

the carcinoma with extension to

the right orbital floor. Surgery took

place on September 9, 1938, using

the McIntosh intubation technique

that had not yet been introduced to

continental Europe. A cheek flap,

using the method of Moure (1922),

was performed and an extensive

right-sided resection of the maxilla

and orbital floor with concomitant

intraoperative instantaneous sec-

tion monitoring. This was also not

in use on the Continent.

The diagnosis using instantaneous

sections showed an R0 resection,

ie, tumor-free resection edges with

the histopathological diagnosis of a

verrucous leucoplakia. A renewed

tumor growth in the orbital floor

area occurred in February 1939.

The sample excision confirmed the

presence of a squamous cell carci-

noma. Prof W Trotter and Exner

described the tumor as inoperable.

Pichler wrote to insist on an addi-

tional operative intervention.

On the advice of the treating doc-

tors, x-ray irradiation was per-

formed by the radio-oncologist Dr

Finzi.

As was to be expected, a necrosis

with perforation occurred in the

area of the right cheek, which led

of the upper middle class of the old

Austria than to political change.

Austria’s absorption into the Third

Reich marked the beginning of

Jewish persecution, and thus of

Freud. Using the 1935 Nuremberg

racial laws, 28 professors and 120

university lecturers were dismissed

from public office.

Austrian Nazis enthusiastically as-

sisted the German anti-Semites.

This was based on a racism that

had a stronger tradition and deeper

roots in Austria and Hungary than

in Germany (Carsten 1976, Kater

2002). By the spring of 1939, almost

2,000 Jewish doctors in Austria

were forced to give up their profes-

sion.

In spite of his neoplastic disease,

Freud, then 82, decided to emi-

grate but was unable to obtain an

exit permit, as the Nazis already re-

garded Freud as the personification

of the Jewish enemy.

Faced with this situation, Pichler

managed to convince Dr Sauer-

wald—the party commissioner

responsible for exit permits—that

Freud’s scientific works were not

concerned with “Jewish villanies”,

and he succeeded in getting Sauer-

wald to study Freud’s writings.

Sauerwald then suppressed all in-

criminatory documentary evidence

against Freud, while Pichler dealt

with the secret police. Freud left Vi-

enna on the Orient Express on June

4, 1938.

Before departure, a last examina-

tion was carried out by Pichler on

June 2, 1938, who detected no re-

currence of the tumor.

to unbearable pain. In one of his

last letters, Freud wrote on July 5,

1939: “My world is a small island of

pain floating on an ocean of indif-

ference.“

Sigmund Freud fell into a coma on

September 21 and died at 3am on

September 23, 1939.

SummaryProf Pichler’s treatment of the 14

year long neoplastic disease en-

abled Freud to create his impressive

later works. Thanks to the skilful

intervention of Pichler, Freud was

able to leave Austria for Britain and

thereby avoid the fate of many of

his compatriots.

Max Schur, the doctor and poet,

wrote the following in 1972 about

Prof Pichler: ”He was an exception-

ally kind-hearted and human per-

son. A surgeon who was not afraid

of performing radical interventions

when they were necessary. His as-

sociation with Sigmund Freud was

one of extreme respect, tact, and

politeness. Pichler was fortunately

a man of obsession, in the best spir-

itual meaning of the word.”

BibliographyLiterature in the author’s

possession.

12 13 14 15

12 Prof Hans Pichler 1936.

13 Nitrous oxide anesthesia 1936 Munich University.

14 Pogrom in Vienna 1938.

15 Departure on the Orient Express Vienna-Paris-London. Princess Marie Bonaparte, American ambassador Bulitt.

16 Insuffl ation anaesthesia 1940 using the method of McIntosh.

16

10 AODIALOGUE 1 | 07

During his time within the AO organization,

he first studied polylactides as candidates to

replace internal fixation devices. He soon real-

ized that constructs made of this material may

also serve as bone substitute materials, and that

membranes and scaffolds were most valuable for

tissue engineering purposes. In great detail, he

investigated and developed different composi-

tion, manufacturing, and sterilization processes

to make sure the materials fulfilled their func-

tion in the human body. In later years in Davos,

his attention turned again to polyurethanes,

another bioresorbable material, which can be

tuned to provide optimal conditions for bone as

well as cartilage tissue engineering. He not only

conducted excellent research, but had his own

and his team’s work published in renowned,

peer reviewed journals. No less than 150 pub-

lications were the result of his tireless work and

maybe twice as many abstracts were presented

in the leading orthopedic and biomaterials meet-

ings. He was active right up until the end of his

career at the AO. Indeed, two of his final proj-

ects on isosorbide-based biodegrad-

able polyurethanes and the use of

various plant polyprenols to biolize

biodegradable polymeric scaffolds

to promote cell attachment, growth

and proliferation, and/or to prevent

tissue adhesion may yet yield great

rewards.

Prof Gogolewski provided his ex-

cellent knowledge of the chemistry,

synthesis, and production of resorb-

able biomaterials as well as their

behavior in the human body freely

to everyone interested in this sub-

ject. This knowledge allowed him

to realistically assess the potential

of a future treatment option. He

has been a cornerstone of the AO

Research Institute for 18 years and

contributed greatly to our expertise

in this area. I sincerely thank him

for his innovative work and tireless

dedication and wish him a long and

happy retirement.

Erich SchneiderDirector AO Research Institute

erich.schneider@aofoundation.org

Professor Sylwester Gogolewski is a well-known

figure to many within the AO. He has worked

on bioresorbable polymers in the AO Research

Institute for the past 18 years. After a long ca-

reer spent mostly in the world of research, this

knowledgeable man whose vim and vigor belies

his age, has left Davos and the AO to return to his

home country.

Sylwester was born in 1936 in Warsaw, Poland.

He received his Master’s Degree from the Uni-

versity of Lodz, where he specialized in chemis-

try. His doctoral dissertation dealt with nylon, a

modern polymer at that time and his habilitation

with the crystallization of polyamides. Moving

up in his academic career, he became Associate

Professor and Head of the Polymer Department

at the Technical University of Zielona Góra. 1980

was the year he made Western Europe his per-

manent home and became a Visiting Professor

at the Department of Polymer Chemistry in the

University of Groningen, the Netherlands. Even

though he only stayed there for three years, his

work on vascular prostheses and

polyurethanes carried out in this

institution inspired him again and

again throughout the years. In

August 1983 he decided to leave

the university to join a Swedish

research and development com-

pany in the French speaking part

of Switzerland. He joined the AO

Foundation in 1988 with the task of

researching and developing resorb-

able materials for use in fracture

treatment.

Sylwester Gogolewski

On his retirement, a tribute to his contributions to the AO.

11

AO in Scotland

Chris OliverConsultant Trauma Orthopaedic SurgeonEdinburgh Orthopaedic Trauma Unit

cwoliver@rcsed.ac.uk

Edinburgh has a long and distinguished history

in medicine and surgery, with many advances

pioneered in the city or by Edinburgh graduates.

Notable surgeons include John Hunter, anato-

mist and “founder of scientific surgery“ in the

late 18th century; Robert Liston, who performed

the first operation under anesthesia (ether) in

1846; and Sir James Simpson, who discovered

chloroform the following year, by testing it on

his dinner guests until they slid under the table!

Other “firsts” include Charles Bell, who identi-

fied the nerve functions in 1811 and founded

the science of neurology; James Syme, pioneer

of plastic surgery; the first hypodermic syringe

(Alexander Wood 1853). In the early days,

anatomy students had difficulty obtaining suf-

ficient subjects for dissection, and the need was

filled by grave robbers—the “resurrectionists”.

In 1829 Messrs Burke and Hare streamlined the

process by murdering and then selling their vic-

tims directly to the unquestioning university‘s

surgical department. The pioneering trail con-

tinues through Alexander Fleming, discoverer of

penicillin (1928) and anti-typhoid vaccines, the

UK‘s first successful kidney transplant (Michael

Woodruff, 1960) and the cloning of the famous

Dolly the Sheep (Ian Wilmut, 1996).

The 4th Scottish AO Principles of Operative

Fracture Management Course for Surgeons was

held in March 2007 in Edinburgh. The four day

course was held at the new surgical skills centre,

Quincentenary Hall (www.surgeonshallcom-

plex.com) at the Royal College of Surgeons of

Edinburgh (www.rcsed.ac.uk). The Quincente-

nary Hall is a new state-of-the-art surgical skills

complex in a versatile modern building adjacent

to the historic Surgeons’ Hall. The course chair-

manship was taken over by Mr Clark Dreghorn

(Glasgow) and Mr Andy Kent (Inverness) this

year, replacing Mr Chris Oliver and Mr John Ke-

ating from the Edinburgh Orthopaedic Trauma

Unit who have led the course since its inception

in 2004. The faculty is mostly Scottish with sur-

geons from Edinburgh, Glasgow, Stirling, Pais-

ley, Aberdeen, and Inverness. On this occasion

Dr Maarten van der Elst came from the Neth-

erlands as visiting faculty. The course now ca-

ters for 48 participants of which half come from

Scotland. The AO Principles Course in Scotland

has not only allowed the participants to develop

skills but has also allowed the Scottish surgeons

to become a cohesive force in trauma orthopedic

surgery. The high standard of the Scottish train-

ing workshops, lectures, and discussion groups

has been internationally recognized.

community zone events

12 AODIALOGUE 1 | 07

Davos Courses 2006

Assessment and evaluation Piet de BoerDirector AO EducationDübendorf, Switzerland

piet.deboer@aofoundation.org

Assessment of a course and evaluation of indi-

vidual presentations within that course is a com-

plex and controversial area. Everyone is agreed

that the purpose of AO Education is to improve

the quality of care given to patients by the course

participants after the course. We are probably

several decades away from being able to measure

this effect, but the Davos Courses in 2006 were a

landmark in our progress towards this goal.

Davos 2006 saw two new programs rolled out for

the first time—needs assessment and the Audi-

ence Response System (ARS) based course eval-

uation system.

Needs assessment This is the brainchild of Bob Fox and Joe Green,

our US based educational consultants. The proj-

ect began following an AOEB brainstorming re-

treat at the triennial Alumni event in Sardinia

in 2005. Individual course chairmen around

the world were asked to define key competen-

cies for the courses that they were running. A

competence is something that you wish the

course participants to acquire as a result of the

course. Twelve competencies were defined for

the Principles course and twelve for the Advanc-

es course. For the principles course, a different

group of course chairmen were asked to write a

series of questions with yes/no answers, relating

to the competencies that had been defined, to be

able to assess the knowledge level of the course

participants before the course began.

Course participants were contacted online some

four weeks before the course and asked to look at

the competencies that had been defined for their

course. They were asked to evaluate how impor-

tant each of these competencies were on a scale

of 1–5 and to record how well they thought they

already understood these competencies. The dif-

ference between the two scores reflected a mea-

sure of how motivated the course participants

were. Clearly if a course participant has a high

perceived need for a given competence and thinks

that he has a low level of current knowledge then

that course participant will be extremely moti-

vated to learn. Following completion of this per-

ceived needs assessment, course participants on

the Principles course were then asked a series of

13community zone events

The significance of these results is two fold.

Firstly, we have shown that this system can be

made to operate reliably and provide reproduc-

ible results. Secondly, because AO now possesses

and uses such a system we can truly say to any

CME authority that the contents of our courses

are determined by the needs assessment of our

course participants—the highest level of quality

as dictated by the CME regulating authorities.

Furthermore, the results with regards to the per-

ceived needs of our course participants will help

determine the future structure of courses.

Audience Response System ARS based course evaluation of individual pre-

sentations was carried out on all AO courses this

year. Course chairmen were asked to define five

key learning objectives for their courses. Course

participants were asked at the start of the course

how important these were to their everyday

practice. At the end of the course, course partici-

pants were asked about these key learning objec-

tives. They had five choices:

1. Did not learn anything new.

2. Learned something new, but do not want to

use it in my practice.

3. Learned something new, but probably won’t

be able to use it in my practice.

4. Reconfirmed that what I do in my practice set-

ting is appropriate.

5. Learned something new and plan on using it

in my practice

It can be seen that answers 4 and 5 represent a very

positive learning experience from the course.

yes/no questions relat-

ing to the individual

competencies. Analy-

sis of these results gave

an understanding as

to the current level

of knowledge of the

course participants.

Following the course,

the course partici-

pants were asked to

fill in the same needs

evaluation form and to

complete a set of ques-

tions relating to the

competency.

ResultsThe results of the per-

ceived needs of the

course participants from Davos closely reflected

those of course participants in Leeds, Sapporo,

Reno, San Diego, Stockholm, and Dubai. Over-

all, course participants were extremely highly

motivated and it is interesting that they rated

the importance of the individual competencies

quite consistently. The need to assess and treat

a haemodynamically unstable pelvic fracture in

an emergency situation was rated by all course

participants, outside Japan, as being the most

important skill they could acquire from the Prin-

ciples course.

Assessment of the yes/no questions showed that

approximately 60% of the course participants

got the question right and 40% wrong. This re-

flects the relatively junior nature of our Princi-

ples course participants in Davos and this data

is similar to that collected in Leeds and in Uru-

guay.

Following the course, the perceived needs of the

course participants dropped dramatically. That is

to say that the course participants assessment of

the course was extremely favorable. Disturbing-

ly, the results from the yes/no answers however

showed virtually no change. We are, at present,

working with colleagues from AO North Ameri-

ca to change the knowledge assessment tool to a

more sophisticated system, to try to better assess

the true level of knowledge of our course par-

ticipants.

Perceived needs—participants fill in:

D Desired level of competence (1–5)

P Present level of competence (1–5)

How to read gap values:

≥ 3 Fear

1.6–2.9 High interest & motivation

≤ 1.5 Low interest & motivation

14 AODIALOGUE 1 | 07

At the end of each lecture, discussion group,

and practical course, participants were asked to

evaluate the presentation. They were asked to

evaluate the presentation on a scale of 1–5, as to

whether the presentation had been relevant to

their practice. They were then asked to evaluate

the performance of the individual faculty mem-

ber concerned in the presentation.

ResultsThe results with regards to the five key learning

points for the courses showed that most courses

had been overwhelmingly successful in achiev-

ing their learning objectives. Particularly suc-

cessful courses were the Swiss Residents’ course

held the first week in Davos and the English

Principles course held in the second week.

Most courses were extremely well rated by the

course participants. However, comparison of the

individual courses did show that some courses

were consistently more successful than oth-

ers with regards to the course participants’ as-

sessment. This information was fed back to the

course chairmen and individual faculty mem-

bers and will form a basis for the reevaluation of

individual courses in the future.

The data with regards to the in-

dividual presentations revealed a

hitherto unknown fact. If an in-

dividual presentation was rated by

the course participants as not being

relevant to their practice, then the

course participants almost invari-

ably rated the performance of an

individual faculty member as being

poor. The correlation between

these two figures, which has never

been recorded before in education

research literature, will form the

basis for further studies.

Individual faculty were given infor-

mation with regards to their own

particular performance, but were

not given information about others.

The assessment of their own per-

formance could be gauged by their performance

scores and also by the difference in the scores be-

tween the relevance scores and the performance

scores. In the future, we hope to be able to ana-

lyze conspicuously good or less than average per-

formance and provide advice to the individual

faculty member as to how to improve their own

performance.

Overall, the amount of information that we have

gained about the Davos 2006 Courses is huge.

Well over a quarter of a million pieces of infor-

mation were collected and evaluated and the re-

sults give us the most comprehensive view of the

success of Davos in 2006. This program will con-

tinue in the years to come and allow us to get an

understanding of how things are changing and

hopefully improving with the years. Individual

course chairmen now get useful information

with regards to planning of future courses and

individual faculty members get, for the first time,

an objective assessment of their own particular

performance. Future developments will include

the refining of the question and answer section

of the needs assessment and an introduction of

this into the Advances courses. We hope that in

2007 a more detailed needs assessment will be

able to be carried out for certain other courses

including the orthopedic geriatric course.

The next development in assessment will be the

introduction of a research project entitled “The

Barriers Project”. The barriers project attempts

to look at the barriers that exist for surgeons

who wish to change their practice but are not

able to do so. A pilot project carried out in 2005

revealed that over 75% of the Advances course

participants were unable to change their prac-

tice—even if they wanted to—the most common

reason being an inability to access or afford the

equipment. This research project was approved

by the AOEB at its March meeting and prelimi-

nary results should be available in early 2008.

The barriers project takes us another small step

towards the end process of evaluation of our ed-

ucational events—evidence that we change the

practice of surgeons so as to improve the results

of patient care.

15

A week to rememberAO Educators’ Seminar for ORP, Davos 2006

Yvonne MurphyRegistered NurseBirmingham, United Kingdom

yvonne.murphy@vhb.nhs.uk

A group of 22 ORP educators from England,

USA, Australia, New Zealand, Austria, France,

Germany, Belgium, Norway, Sweden, Switzer-

land, Mexico, Brazil, Israel, Iran, Malawi, and

China gathered at the 6th ORP Educators’ Semi-

nar, in Davos, in December 2006 for an advanced

learning experience. The seminar’s aims were to

support the ORP in acquiring and developing ed-

ucational skills in order to contribute effectively

to the AO education program within their coun-

try and worldwide and to extend and develop

the AO ORP Alumni community. Faculty mem-

bers for this seminar included Susanne Bäuerle,

Rossanna Fornazzari, Lisa Hadfield-Law, David

Pitts, Donna Russell-Larson, and Isabel Van Rie.

Most of the course participants arrived on Sat-

urday, December 9, and stayed in the same hotel

allowing everyone to meet and bond almost

instantly. The first meeting of the participants

occurred at the hotel dining room where one

long table was reserved for the ORP. Participants

introduced themselves as they arrived and every-

one felt very welcome and comfortable. This was

the start of a group friendship that went from

strength to strength.

The course began early Sunday morning as the

group met at the hotel reception and were intro-

duced to some of the course core faculty. The wel-

come meeting for the entire surgical faculty was

held at the conference centre. I was astounded

at how many faculty members it took to run the

courses in Davos. The room was enormous and

almost full. The President of the AO Foundation,

Chris van der Werken, welcomed everyone with

an inspiring talk as did Piet de Boer, the Director

of AO Education.

community zone events

16 AODIALOGUE 1 | 07

Our group’s first task was to observe

the Principles precourse meeting.

We were asked to identify three

items we had learned from this ob-

servation. Although we all could

certainly identify more than three

items that we could use in our own

precourse meetings, it was evident

that a clear course plan of action,

review of the practical exercises,

and the opportunity for faculty to

discuss their concerns were the

most important items. Our group

was made to feel very welcome by

the surgical faculty and we were

encouraged to introduce ourselves

alongside our colleagues.

After the precourse meeting, the

group separated to do different

things including lunch, going back

to the hotel to rest etc. I was in a

group of five that chose to attend

the Synthes welcome get-together

on Jakobshorn Mountain. This was

an amazing experience for me as I

had never skied or been on a snow

covered mountain before. The trip

up the mountain made me a little

nervous when I realized how high

up we were going, but once there

I wouldn’t have missed it for any-

thing. The sun was shining yet it was snowing

and the snow looked like glitter falling from the

sky. In the midst of this there was a barbeque,

music playing, and mulled wine to keep out the

cold. It was a fantastic atmosphere and just one of

the many wonderful memories I will take from

Davos and keep with me always.

In the evening we returned to the conference

centre for the main welcome reception. After

the welcome we attended a dinner to meet the

course directors and core faculty who would be

facilitating the ORP educators’ seminar. This

was another great learning experience. Every-

one shared stories about their countries and how

courses for ORP were organized in each one, as

well as generally getting to know each other.

This was the first of many dinners together.

Monday was the first day of our seminar. The

president of the AO Foundation spoke about

the importance and value of ORP in AO educa-

tion. Following this, we went on to examine the

reasons we had come to the educators’ seminar.

Typical answers to this question included, “Be

able to give presentations and feel confident in

doing this”, “Develop my teaching skills”, “To

gain knowledge and ideas to take back to my

own courses”, “Share ideas and meet people”. We

heard a talk about valuing our differences. The

ORP faculty who travel to present courses in dif-

ferent countries spoke to us about the different

cultures and how doing and saying something

one way in one country may not be acceptable in

another, and how this needed to be recognized

and overcome in order to deliver a good course

for participants.

After observing a practical exercise involving

surgeons we were asked to identify three items

that had gone wrong. It was a fantastic learning

experience for our group. We went away with

the knowledge of what can go wrong even with

the best planning and realized how important

singing from the same song sheet is. I also think

the course director learned from us that day as

I know the constructive feedback was available

for him to see.

Finally we learned about presentations, the one

area where everyone seems to lack confidence.

We learned that “Proper preparation and prac-

tice prevents poor performance”. This includes

set, dialogue, and closure, and keeping slides

clear, concise, and simple. We also learned to in-

tegrate questions to make it interesting and to

ensure that the participants are awake!

Tuesday was another full and exciting day about

teaching and practicals. Developing the roles of

a table demonstrator and practical moderator

require guidance and support, and this seminar

was the ideal place to get it. After preparing and

running a practical, feedback was then given to

us by our observing faculty.

The day did not finish until late into the evening,

as we had been given the task of preparing a pre-

sentation for the following day on what we had

learned so far. It was a particularly difficult task

for my friends who did not have English as their

first language. However, it brought the whole

group together even more and created a strong

bond between us. Everyone helped each other in

Participants enjoying both the Davos weather and the seminar.

17community zone events

whatever way they could. It was hard work but

extremely rewarding.

Wednesday was “the performance”. This was a

day full of anxiety for us all, even though we

knew we were presenting to our friends. Need-

less to say it was a successful day full of emo-

tion as we all wanted everyone to do well. Those

without English as a first language did particu-

larly well. I am English and I understood every

presentation as they were all superb. The presen-

tations were videotaped and we have a copy to

look back on and learn from. The seminar from

this moment on seemed much more relaxed for

all of us as we felt that we had dealt with our big-

gest challenge, although the hard work and long

days continued.

The day finished with us learning about manag-

ing a discussion group. This type of learning I

particularly enjoy as I find talking to different

people easy. Others in the group found it more

difficult as it was not a familiar environment for

them and one not commonly used in their coun-

try. It was, however, something everyone wanted

to try once they had learned the principles.

At the end of the day we had a wonderful course

dinner where we were taken by horse and sleigh

up a mountain to a traditional Swiss restaurant

and ate to our hearts’ content.

On Thursday we found out about the AO Founda-

tion and how it works. We were informed about

the ORP Alumni and this now made sense to us,

we could see what an excellent group this was

for ORP education. We explored the AO website.

Exploring this was another wonderful learning

experience. I don’t think any of the group real-

ized how much information could be accessed

via this and we were all really enthused.

On Friday, we made the link between the re-

search lab and the patient. The process that the

products have to go through before approval is

quite daunting and extremely interesting. It

made me appreciate why implants cost as much

as they do. We were also given a practical to do

as participants. This was a really exciting ex-

perience for me as it was a tibial nailing and I

specialize in maxillofacial. With the experience

came the realization that teaching and learning

principles are just the same whatever the size of

the implant.

Finally the seminar came to an end and we re-

flected on what we had learned and what we

would do with it. We had all learned a great

deal and knew we had a lot to offer our home

countries. On my return home I made a list of

words that summed up this seminar for me: in-

spiring, excellent, interesting, networking, col-

laboration, realization, development, education,

encouragement, humor, laughter, and above all,

friendship.

The seminar topics inspire discussion.

18 AODIALOGUE 1 | 07

Volume 1 focuses on the basic knowledge and

the principles of fracture management, eg, bio-

mechanics, tools for preoperative planning, soft-

tissue management, different methods of reduc-

tion and fixation, implants. Simultaneously, it

addresses new issues pertaining to internal/ex-

ternal fixation, damage-control surgery, mini-

mally invasive surgery, and biotechnology.

Volume 2 focuses on the management of specific

fractures in different anatomical areas. For each

of these areas there is a separate chapter discuss-

ing the assessment of injuries, surgical anatomy,

preoperative planning, surgical treatment, and

postoperative care, while pointing out pitfalls

and complications. New fixation techniques and

implants have in particular been taken into ac-

count.

DVD-ROM for PC and Macintosh• All illustrations are available for download

and can be used for personal presentations.

• Animations and video clips featuring step-by-

step procedures can also be downloaded for

self-education or use within personal presen-

tations.

• The complete text of the book is available for

quick reference.

For more than forty years, the AO has—true to

its calling—imparted the principles of fracture

management by several publications and special

courses worldwide. The second edition of the AO

Principles of Fracture Management book has

been fully updated and extended to describe the

latest techniques and covers the complete con-

tent of the AO Principles Course of today. It is

now published as a two-volume set and provides

excellent guidance and expertise, compiled by

nearly one hundred contributors, all of whom

are renowned surgeons and members of the AO

faculty. An exceptionally large number of new

illustrations as well as animations and video

clips turn this work not only into excellent ref-

erence books but make them unique learning

tools. Both residents as well as advanced trauma

surgeons will benefit from this concept.

AO Principles of Fracture

ManagementSecond expanded edition

Thomas P Rüedi, Richard E Buckley, Christopher G Moran

AO principles

• Fracture reduction and fixation to restore anatomical relationships.

• Fracture fixation providing absolute or relative stability, as required by the “personality” of the fracture, the patient, and the injury.

• Preservation of the blood supply to soft tissues and bone by gentle reduction techniques and careful handling.

• Early and safe mobilization and rehabilitation of the injured part and the patient as a whole.

For addtional information and to order go to:www.aopublishing.com

19community zone news

AOSpine ManualPrinciples and techniques (Vol 1)

Clinical applications (Vol 2)

Max Aebi, Vincent Arlet, John K Webb

Clinical applications (Vol 2) is based on the novel

interactive sessions within AOSpine courses and

acts as a huge resource of clinical cases with

which the readers’ current knowledge on how to

treat their patients can be expanded.

It presents discussions concerning typical clinical

cases. The reader is involved in the development

of the rationale of treatment, the indications, the

contraindications, the argumentation in favor

of a technique or against one, and the outcome.

Case examples are outlined with learning points

from more than 50 surgeons of which each is a

leader in their surgical field. Clips from AOSpine

live surgery videos enhance the learning experi-

ence.

Max Aebi, Vincent Arlet, and John K Webb are

the three editors-in-chief who oversaw the cre-

ation and publication of this book along with a

team from the AO. More than 80 authors con-

tributed to the manual and the twelve section

editors ensured high standards throughout.

The two volumes offer the reader a combined

total of 1,500 pages and over 3,000 figures. Also

included is one DVD-ROM for both volumes.

Principles and techniques (Vol 1) relates to the

teaching of basic surgical knowledge and surgi-

cal techniques at AOSpine courses and acts as a

foundation for the application of these principles

in clinical practice.

It presents basic scientific and technical prin-

ciples—it provides the reader with the scientific

background to understand spine surgery and it

teaches how to apply these surgical principles

using the instrumentation necessary in a step-

by-step manner with exceptional illustrations;

some critical steps are explained using sequences

from AOSpine teaching videos.

For addtional information and to order go to:www.aospine.org

20 AODIALOGUE 1 | 07

Implant surfaces:Do they have any relevance to the surgeon?

R Geoff Richards

What happens when an implant surface is placed into the body? When inserting a plate, nail, screw, cage, or any other

internal fracture fixation (IFF) device into the body, regard-

less of the material, the implant is coated almost immediately

(within seconds) with a proteinaceous film upon contact with

blood. The proteins come from the blood and provide a provi-

sional matrix for the cells to adhere to. The cells never see the

actual implant surface but this matrix which has adsorbed to

the surface. The surface can determine which proteins absorb

and the orientation of their attachment. Cell adhesion then

usually follows within minutes (fibroblasts and macrophages)

followed by either soft-tissue adhesion or matrix adhesion and

eventual mineralization.

The molecular events at the surface-body interface are con-

trolled by surface properties. In an example of a metal used in

IFF (Fig 1), the actual surface is not the metal but a continu-

ally changing oxide surface. Metal ions diffuse at different

rates into the oxide and oxygen diffuses from the oxide into

the bulk metal. Biological ions are incorporated onto the oxide

along with protein adsorption. The proteins undergo confor-

mational changes over time. All these processes are influ-

enced by: surface topography, greater texture exposes more

discontinuities for interaction with proteins; surface chemis-

try, determines types of intermolecular forces, governing in-

teraction with proteins; surface hydrophobicity, determines

which and how much proteins bind; surface heterogeneity

(nonuniformity), different domains interact differently with

proteins; and surface potential, influences the distribution of

ions in solution and interaction with proteins. The protein

size, charge, and stability affect both the rate of arrival to the

surface and interaction with it. Blood (which has more than

150 proteins) interacts with the surface with albumin being

the most concentrated, having a moderate size (66KD) domi-

nating initial interactions. Fibrinogen (340KD), which has a

lower concentration in the blood has a rate of arrival at least

one hundred times slower, but usually dominates the surface,

exchanging with the faster and weaker bound albumin due to

its greater affinity. This is a very simple view of protein inter-

actions with a surface, but gives an idea of the dynamics of the

biological interactions.

21expert zone

What happens at a soft tissue–implant surface interface? Internal fracture fixation (IFF) implant surface finishes vary

from electropolishing of stainless steel to microrough com-

mercially pure titanium (cpTi) and Titanium-6%Aluminium-

7%Niobium alloy (TAN). TAN is used in LISS plates, locking

screws, and nails and is often mistakenly referred to as tita-

nium by surgeons. In the context of soft tissue, represented in

vitro by fibroblasts, members of my group found rough verses

smooth titanium and steel does not significantly affect fibro-

blast cell adhesion or subsequent growth. Polished TAN also

promoted fibroblast cell adhesion and growth; however both

aspects were seriously compromised on microrough TAN.

Specific aspects of the TAN topography were implicated (rough

beta phase particles within the softer alpha phase matrix),

however, the contribution of its unique surface chemistry to

the cell behavior was unknown. The observation of lower ad-

hesion, spreading, and growth on the surface of standard mi-

crorough TAN necessitated the design of a series of experi-

ments to help distinguish between the effects of material and

those of topography. Coating the standard test materials with

a uniform chemistry provided a practical model to investigate

how surface chemistry and the various topographies interact

in their effect on cells. These experiments eventually drew to

the conclusion that behavioral cues for fibroblasts on metal

implant surfaces were generally confined to the influence of

surface topography over the cue of surface chemistry.

Soft tissues, which are more sensitive to differences in im-

planted materials than bone, can react much quicker to prob-

lematic surfaces and are therefore good biocompatibility mod-

els. Early soft tissue integration with vascularization at the

tissue-implant interface, without liquid filled capsule forma-

tion is often desirable. If a bone is fixed subperiosteally and

the implant is not integrated fully, movement between the

implant and tissue interface may cause the formation of a fi-

brous capsule around areas of the implant which may become

liquid filled. Liquid filled soft tissue fibrous capsules are not

desirable, as they prevent tissue integrating with the implant

and encourage infection because they may reduce vascular-

ization at the biomaterial tissue interface causing the creation

of an immunoincompetent zone and an ideal place for patho-

gen proliferation. Consequently, immune cells are less able to

defend the body against any bacteria that have entered at the

biomaterial tissue interface. Movement of the implant also in-

fluences fibrous encapsulation and may hinder fast integra-

tion into the body and also attract more inflammatory cells to

the site.

Where gliding tissues are concerned, it is thought that a non-

adhering fibrous capsule on the soft tissue side of an IFF im-

plant may reduce the chance of gliding tissues —such as mus-

cles and tendons—adhering to the implant. One example that

requires neighboring tissues to freely glide over the implant is

within orbital fractures where connective tissues should glide

freely and not adhere to the implant surface, or problems with

eye movement can occur. In the case of overlying tendons in

distal radius fracture treatment, current literature describes

how titanium and its alloys tend to lead to more intratendon

inflammatory reactions when compared to steel, leading to

tendon-implant adhesion, tendon damage which prevents

normal tissue motion and may cause limited palmar flexion,

and even tendon rupture. The intrusion of a plate can produce

Ca

P

lionstaMetal/oxide ion diffusion

Biological ion incorporation

Protein absorption

Protein conformational changes

Fig 1 An implant surface is never static within the body and undergoes

continual changes over time, even without mechanical abrasion.

22 AODIALOGUE 1 | 07

friction for the gliding tissue and is liable to become a site for

tissue adhesion and inflammation. These osteosynthesis ap-

plications require the development of surfaces that prevent

soft tissue attachment and irritation, allow tissue gliding, but

maintain their biocompatible properties. It is highly unlikely

that a liquid filled void could occur within these situations,

due to the large movements of the gliding tissues. One way to

reduce the tissue adhesion would be to reduce surface micro-

roughness of the plate in contact with the tissue. Our work

strongly indicates that the surface topography of the titanium

(or even titanium alloy such as Ti15MO, used in hand sur-

gery), rather than the material itself is responsible for this

problem and polishing of the surfaces of plates in contact with

gliding tendons could prevent it. X-ray photoelectron spec-

troscopy results showed that the surface chemistry of anod-

ized polished metals (titanium and its alloys) did not differ

from the chemistry of the standard (as used in clinics) micro-

rough metals. Therefore, the polishing method tested should

be suitable for clinical use, where soft tissue adhesion is not

desired.

Bone With long term or permanent implants, such as spine

cages or chondylar plates in CMF, osseointegration is vital to

their success. Bony integration is increased on implant sur-

faces with higher amounts of microroughness and this is also

seen in the areas of prosthetics (hips and knees) and dentistry

(stents). The majority of research within these areas is into

increasing bony integration.

IFF devices are often removed to avoid: growth disturbances

in pediatrics; delayed infection; implant migration/breakage;

allergic reactions; soft tissue irritation; implant protrusion/in-

trusion (eg, into a joint); build up of fretting particles in unre-

lated organs (from loose multi component implants), as well

as being cosmetically disturbing (protrusion under skin). The

necessity of IFF implant removal is chiefly within the pediat-

ric population. Advocates of life long retention maintain that

difficulty in removing a device due to extraosseous formation

warrant their preservation to avoid complications such as in-

creased operative time, blood loss, and debris contamination.

Problems associated with excessive bony overgrowth account

for ~7% of all complications encountered. In temporary im-

plants such as plating, nailing with the use of screws or the

application of external fixators, minimal bone bonding to im-

plants is desirable for the least traumatic explantation. Strong

bony integration is a disadvantage when considering removal

and the surface microstructure is the major determinant of

this.

Our in vitro work with osteoblasts has shown that surface

polishing acts on a cellular level in that implant surface topog-

raphy influences both osteoblast proliferation and differentia-

tion. We have shown that surface polishing can significantly

reduce expression of osteocalcin, a principle factor involved in

bone mineralization, thus essentially inhibiting the cells abil-

ity to mineralize and form a mature matrix. Moreover, an in-

verse relationship has been observed between osteocalcin

gene expression and total DNA content, indicating a less dif-

ferentiated osteoblast phenotype to be present on polished

smooth samples. The polishing therefore reduces subsequent

mineralization which shows that there is more to surface pol-

ishing than simple macro changes for friction of surface

roughness on the bony integration.

Our recent in vivo work assessed the effect of surface topogra-

phy of TAN and titanium (cpTi) screws with different surface

topographies (polished and microrough) in a sheep cortical

(tibial) and cancellous (rib) bone model over three time peri-

ods of 6, 12, and 18 weeks. The effect of implant topography

on bone adherence was evaluated mechanically by measure-

ment of the peak torque removal force and histologically to

assess the amount of bone present at the surface of the im-

plant. The results demonstrated that polishing both cpTi and

TAN resulted in lower removal torque than standard micror-

ough screws when placed into cancellous bone. Polished cpTi

screws also had a lower removal torque when implanted in

the cortical bone. Polished TAN screws did not have a signifi-

cantly reduced removal torque when implanted in the tibia

but at 12 and 18 weeks, there was a trend for a reduction in

removal torque. Histologically, the polished screws consis-

Fig 2 Scanning electron microscope images of

S aureus bacteria adhered to a) standard micro-

rough TAN, The bacteria are scattered all over

the surface in small clumps of 6 bacteria, b)

electropolished TAN. Bacteria are found to clump

in large clumps, with no small clumps of 6 or less

seen.

23expert zone

tently demonstrated a lower percentage of bone contact than

the standard microrough implants. This study demonstrates

that polishing can reduce removal torque and the percentage

of bone contact in vivo and thereby improve the ease of re-

moval of TAN and cpTi screws placed into cortical and cancel-

lous bone. Where nonpermanent implants are concerned,

having some fibrous material present (as in the case of these

polished cpTi and TAN screws) may be advantageous—be-

cause it can prevent the screw from becoming completely

overgrown by bone, allowing for easier removal without com-

promising its stability within the bone (which is based upon

thread design more than surface structure).

Current in vivo work in our group looks at locked-screw and

plate combinations since many removal problems have been

noted with various designs of such systems. TAN is commonly

used for screws (and plates with LISS) with cpTi being used for

the LCP plate. We believe that excess bone bonding to these

implants is the major cause of the difficulty in removing the

screws from the plates. The purpose of the study is to assess

the effect of surface treatment of LCPs upon direct bone con-

tact after 6, 12, and 18 month implantation times in sheep

tibial cortical bone. We anticipate that the polished surfaces

will demonstrate decreased bone bonding and decreased ex-

traction forces. The results of this investigation could have sig-

nificant impact on the surface design of locking-head screws

and LCP plates to avoid the clinical problems during removal

of the implant. A second area we are working on is intramed-

ullary nailing. IM nails are composed of either stainless steel

or TAN. TAN is preferred due to its better biocompatibility and

mechanical properties. However excess bone bonding to the

TAN nails, resulting in difficulty in their removal has been

described. TAN has a microrough surface since the alloy is a

mix of soft α and harder ß phases which gives a micro spiked

morphology after surface processing. This surface integrates

extremely well with bone (as shown in our previous work

with cortical screws in vivo and discs in vitro). We know that

polishing TAN smoothes these micro spikes within the TAN

surface, which should reduce the amount of direct bone con-

tact for the nails as well as removal torques. The difficulty in

removing nails due to excess bone on-growth has not been

described for steel, which is clinically used with a smooth sur-

face. After a 12 month implantation period the nails will be

extracted by a pull-out test and some nails will remain in situ

for histomorphometric evaluation. We anticipate that the pol-

ished TAN nails will demonstrate decreased bone bonding

and extraction forces. This finding could be used to recom-

mend changes to current surface treatments of intramedul-

lary nails to reduce complications seen with nail removal, es-

pecially in rapidly growing bone in pediatrics.

Infection Surfaces of IFF implants are generally designed to

encourage soft and/or hard-tissue adherence, eventually lead-

ing to tissue integration. Unfortunately, this feature may also

encourage bacterial adhesion. Soft-tissue infections and os-

teomyelitis are serious complications associated with im-

plants, particularly with open fractures, external fixation de-

vices, and intramedullary nailing. Consequences of implant-

associated infections include prolonged hospitalization with

systemic antibiotic therapy, several revision procedures, pos-

sible amputation, and even death. Serious complications are a

great problem due to the emergence of antibiotic resistant bac-

teria such as methicillin-resistant Staphylococcus aureus

(MRSA). Hence modifying the actual metal implant surface to

inhibit or reduce initial bacterial adhesion may be an option.

Our recent work has looked at visualization and quantifica-

tion of Staphylococcus aureus, Staphylococcus epidermidis, Strepto-

coccus mutans, and Pseudomonas aeruginosa adhering to various

surfaces including standard microrough cpTi and TAN sur-

faces, electropolished cpTi and TAN surfaces, and standard

electropolished stainless steel. Significantly more live bacteria

were observed on standard microrough TAN surfaces than on

the other metal surfaces. There was no significant difference

in the amount of bacteria found on the other surfaces. Such

an observation suggests that the standard microrough TAN

surfaces encouraged S aureus adhesion, and could lead to

higher infection rates in vivo. Hence polishing TAN surfaces

could be advantageous in osteosynthesis areas in minimizing

bacterial adhesion and lowering the rate of infection. In the

case of infection prevention chemistry and alternative tech-

nology with active biological surface modifications for pre-

vention of bacterial adhesion and infection at the implant site

will have a stronger future than pure topographical modifica-

tion.

Fig 3 Modified universal humeral

nails used in our current study on

nail removal. Left, polished test TAN

nail with mirror like surface, middle,

standard microrough surface TAN

nail with matt surface, and right,

polished standard surface steel nail

with smooth surface.

24 AODIALOGUE 1 | 07

Geoff, whose degree was in cell and immunobiology, com-

pleted a masters in electron microscopy and received a PhD in

cell adhesion at The University of Wales, Aberystwyth. He has

authored over 50 peer reviewed papers and more than 200

abstracts, has 1 patent and 2 are pending. He has supervised 6

PhDs, 13 masters, 3 medical theses, and 2 diplomas with sev-

eral more ongoing. He is cofounder and Editor-in-Chief of the

first and only online open access biomaterials journal: “Euro-

pean Cells & Materials” (www.ecmjournal.org) which has

4,850 registered readers worldwide and is indexed by Medline

among others. Geoff is an honorary Senior Research Fellow at

the University of Glasgow, honorary lecturer at Aberystwyth

University and has a 3 year visiting Professorship at Tokyo

Medical and Dental University, Japan. He is President of the

Swiss Society for Biomaterials and has organised many con-

ferences and symposiums within this field.

We have developed topographies to answer clinical questions

without having to worry about shelf life and other concerns

with chemical/biological modifications. Topographical modi-

fications can be robust, cheap, and permanent, whether in

storage or in the body and (in the case of metals) can override

other cues of information to the cell such as chemistry. This

gives topographical surface modification a good solid platform

to start from. On top of this, topographical surface modifica-

tions, unlike chemical modifications, should not need extra

approval before clinical use. Polishing various implant sur-

faces has the potential to reduce the torque required for their

removal, reduce soft tissue problems, and in the case of TAN,

reduce bacterial attachment.

In situations with either hard or soft tissue interactions with

biocompatible bulk materials, the ‘implant biocompatibility’

is determined more by the design and surface characteristics.

Without surface modification an implant may be biocompati-

R Geoff Richards, Prof Dr SciProgram Leader Bio-performance of

Materials & Devices

AO Research Institute, Davos, Switzerland

geoff.richards@aofoundation.org

Fig 4 4-hole LCPs used with locking screws in our current cpTi

(silver), standard microrough cpTi (gold), polished anodized

titanium (blue) and electropolished stainless steel control

(silver).

ble in one anatomical situation, yet not in another. Polishing

is not the answer to everything, though may have use in cer-

tain clinical applications as mentioned within this article.

There is no ‘one surface’ for all applications and surfaces on

one implant interacting with different tissues need to be con-

sidered as separate entities.

25expert zone cover theme polytrauma management

Platelet-rich plasma for bone healing—to use or not to use?

Sebastian Lippross, Mauro Alini

Introduction At the beginning of the 21st century, the clini-

cal application of platelet-rich plasma (PRP) was considered a

breakthrough in the stimulation and acceleration of bone and

soft tissue healing. Since then, its use has been predominantly

in maxillofacial surgery as an autologous additive to bone

grafts and soft tissue transplants, although other indications

such as chronic diabetic ulcers and some standard orthopedic

procedures have been suggested. This article will clarify the

rationale behind the clinical application of PRP by reviewing

the literature and outlining some of our own observations in

basic research.

Platelets and the growth factors they release are essential for

regulating the cellular events that follow tissue damage. They

adhere, aggregate, form a fibrin mesh, and subsequently re-

lease a large variety of growth factors and cytokines. At least

15 different factors are known to be contained within plate-

lets [1–3], including platelet derived growth factor (PDRF-bb,

-ab und -aa isoforms), transforming growth factor-beta (TGF-

beta, -beta1 and -beta2 isoforms), platelet factor 4 (PF4), in-

terleukin 1 (IL-1), platelet-derived angiogenesis factor (PDAF),

vascular endothelial growth factor (VEGF), epidermal growth

factor (EGF), llatelet-derived endothelial growth factor

(PDEGF), epithelial cell growth factor (ECGF), insulin-like

growth factor (IGF), osteocalcin (Oc), osteonectin (On), fi-

brinogen (Fg), vitronectin (Vn), fibronectin (Fn) und throm-

bospontin-1 (TSP-1). The impact on bone and tissue regenera-

tion of most of these factors has been recognized by many

authors [4–13]. As opposed to an artificial composition of re-

combinant proteins, PRP maintains the natural concentra-

tions within a cocktail of growth factors acting on multiple

pathways [14]. Furthermore, artificial recombinant growth

factors require further synthetic or animal proteins as carri-

ers. PRP in contrast serves as a natural carrier itself [15].

Thereby PRP can mimic the highly efficient in vivo situation

much more closely than a custom designed protein prepara-

tion.

As platelet concentrates can be prepared from whole blood

within a short time using relatively simple methods, they have

the potential to be an immunogenically inert additive to pro-

mote rapid healing and tissue regeneration. Preparation of

platelet concentrates usually requires a two step centrifuga-

tion procedure [16]. In the first step full blood is divided into

a platelet-containing and a cell-containing fraction [17]. Dur-

ing the second step, which is high speed centrifugation, plate-

lets can be sedimented and rediluted to the desired volume of

plasma (usually 1/10 of the initial blood volume) yielding

platelet concentrations of more than 1,000,000 platelets/μl

[15, 17]. To release the growth factors and cytokines, platelets

need to be activated. In vivo this happens through platelet

agonists like thrombin, collagen, ADP, serotonin, and throm-

boxane A2. For experimental purposes, bovine thrombin and

CaCl2 are the most commonly used agents. In our own studies

26 AODIALOGUE 1 | 07

we have demonstrated equal efficacy for freeze-thaw-activa-

tion of PRP [18]. In clinical practice PRP is used as a liquid,

made from 50–100ml of full blood that quickly forms a gel

when applied with thrombin. Several companies have devel-

oped kits and devices for automatic preparation during surgi-

cal procedures.

Although the general concept seems plausible, controversy re-

mains about whether PRP and other platelet preparations

meet the high expectations set by the clinical demands. For

the practitioner it appears very difficult to obtain information

on the actions and the possible risks of using platelet concen-

trates.

Clinical safety considerations Clearly an autologous prepa-

ration does not bear the risks of transmissible diseases nor of

immunogenic reactions. If commercially available devices are

used, FDA approval will usually ensure that the preparation

process is carried out in a sterile and pyrogen free manner. We

are not currently aware of any serious adverse effects that

have occurred when PRP was used for wound healing and

bone grafting. Still, a possible risk arises from bovine throm-

bin that is used to activate PRP. Coagulopathies due to anti-

body formation against thrombin, Factor V, and Factor XI

have been reported after cardiac surgery [19, 20].

Basic research—in vitro and in vivo effects of autologous platelet concentrates While there are numerous case stud-

ies and small clinical trials on the clinical applications, knowl-

edge about the underlying effects at the cellular level is limit-

ed. Nevertheless, PRP has been shown to stimulate cell

proliferation of osteoblasts and fibroblasts and to upregulate

osteocalcin in these cells [21, 22]. In a recent study by our

own group we demonstrated the differentiation of mesenchy-

mal stem cells (MSC) into bone forming cells in the presence

Application Type of study Study design Conclusion Reference

Treatment of intra-

bony defects

Comparative

controlled clini-

cal study

70 interproximal intrabony osseous

defects were treated with PRP and a

ceramic porous hydroxyapatite (HA)

scaffold or HA and saline

Treatment with PRP and HA led to

significantly more clinical im-

provement than HA and saline

[32]

Treatment of intra-

bony defects

Randomized

clinical trial

(split mouth,

double masked)

Bilateral periodontal intrabony de-

fects were matched in 13 individuals

and treated only with a bovine xeno-

graft or with PRP

PRP significantly increased the

clinical periodontal response of le-

sions treated with xenogenic bone

grafts

[33]

Treatment of

infrabony defects

Prospective case

series

Five similar bilateral paired infrabony

defects were treated with autologous

platelet concentrate (APC) or a biore-

sorbable barrier membrane (MEM)

Similar gain in clinical attachment

level and probing depths in APC

and MEM treated groups

[34]

Lumbar spine fusion Prospective re-

view compared

to historical

results

23 individuals underwent transforam-

inal lumbar interbody spinal fusion

(TLIF) with PRP compared to histori-

cal results

2-year minimum follow-up

showed faster healing in the PRP

group, but no significant differ-

ence in the pseudarthrosis rate

was observed

[35]

Total ankle replace-

ment

Comparative

Study

114 and 66 Agility total ankle replace-

ments were performed without and

with autologous concentrated growth

factors for distal syndesmosis fusion

Autologous concentrated growth

factors appeared to make a sig-

nificant positive difference in the

syndesmosis union rate in total

ankle replacements

[36]

Treatment of mandib-

ular continuity de-

fects in tumor cases

Prospective

study

44 individuals were treated with bone

graft and PRP and bone graft alone

Maturity index of bone grafts

with PRP was higher than in bone

grafts alone

[37]

Table 1 Application in bone healing

27expert zone cover theme polytrauma management

of PRP [18]. An increase in growth and differentiation of PRP-

treated periodontal ligament cells has been shown by two

groups [10, 23]. Further investigation revealed stimulation of

the mitogenic (ie, transforming) response to PRP in human

trabecular and rat bone marrow cells [24, 25]. Additionally,

we were able to demonstrate a strong effect on the expansion

of endothelial progenitor cells by platelet-released growth fac-

tors [26].

In vivo studies do not support the positive actions of PRP. In

fact, in one of the most recent investigations PRP decreased

the osteoinductivity of demineralized bone matrix in nude

mice [27]. Other researchers performed trials on various ani-

mals and reported no beneficial effect of using PRP for bone

healing [28] or suggest a low regenerative potential for its use

in combination with xenogenic bone grafts [29]. Some studies

also show effective augmentation of porous biomaterial in rats

[30] and sheep [31]. Careful analysis of these studies reveals

that none are scientifically comparable. Therefore, we cannot

draw an overall scientific conclusion of PRP actions in animal

models.

Clinical trials and case studies Case reports and small clin-

ical trials have been reported in craniomaxillofacial surgery

as in other specialties. Table 1 and table 2 display a selection of

such studies which overall support the beneficial effect of PRP

and other platelet concentrates. As previously mentioned, in

animal studies the two main factors making it almost impos-

sible to compare any two of the studies published are the lack

of a standardized PRP preparation protocol (Table 3) and the

lack of commonly accepted evaluation criteria.

Application Type of study Study design Conclusion Reference

Treatment of chronic

ellbow tendinosis

Cohort study Out of a cohort of 150 patients with

chronic elbow tendinosis, 15 were

given one injection of PRP, and 5

were given one injection of bupiva-

caine

Pain was reduced in patients

treated with PRP compared to the

control group in this pilot study

[38]

Treatment of diabetic

foot ulcers

Prospective

randomized

controlled trial

40 individuals were randomized into

a PRP- and saline-gel group and fol-

lowed up for 12 weeks

Significantly more ulcers healed in

the PRP group

[39]

Treatment of diabetic

foot ulcers

Meta-analysis More than 25,000 cases of diabetic

foot ulcers were treated with and

without platelets

Ulcers treated with platelet con-

centrate were significantly more

likely to heal

[40]

Table 2 Other applications

Device Preparation time Platelet yield (whole blood) as stated by manufacturer

Company

GPS

(gravitational platelet separation)

12 min Up to 8 Cell Factor Technologies

PCCS (platelet concentrate collec-

tion system)

20 min Up to 7 Implant Innovations

Symphony II 15 min Up to 6 DePuy

SmartPReP 15 min Up to 9 Harvest Technologies Corp

Magellan 15 min Up to 10 Medtronic

Table 3 Commercially available preparation systems

28 AODIALOGUE 1 | 07

Bibliography

1 Eppley BL, Woodell JE, Higgins J (2004) Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg; 114: 1502–1508.

2 Weibrich G, Kleis WK, Hafner G, et al (2002) Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg; 30:97–102.

3 Yazawa M, Ogata H, Nakajima T, et al (2003) Basic studies on the clinical applications of platelet-rich plasma. Cell Transplant; 12:509–518.

4 Bostrom MP, Saleh KJ, Einhorn TA (1999) Osteoinductive growth factors in preclinical fracture and long bone defects models. Orthop Clin North Am; 30:647–658.

5 Boyan BD, Ranly DM, Schwartz Z (2006) Use of growth factors to modify osteoinductivity of demineralized bone allografts: lessons for tissue engineering of bone. Dent Clin North Am; 50:217–28, viii.

6 Einhorn TA (1995) Enhancement of fracture-healing. J Bone Joint Surg Am; 77:940–956.

7 Glowacki J (1998) Angiogenesis in fracture repair. Clin Orthop Relat Res; S82–S89.

8 Laurencin CT, Ambrosio AM, Borden MD, et al (1999) Tissue engineering: orthopedic applications. Annu Rev Biomed Eng; 1:19–46.

9 Logeart-Avramoglou D, Anagnostou F, Bizios R, et al (2005) Engineering bone: challenges and obstacles. J Cell Mol Med; 9:72–84.

10 Lucarelli E, Beccheroni A, Donati D, et al (2003) Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials; 24:3095–3100.

11 Mistry AS, Mikos AG (2005) Tissue engineering strategies for bone regeneration. Adv Biochem Eng Biotechnol; 94:1–22.

12 Salgado AJ, Coutinho OP, Reis RL (2004) Bone tissue engineering: state of the art and future trends. Macromol Biosci; 4:743–765.

13 Street J, Bao M, deGuzman L, et al (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci USA; 99:9656–9661.

14 Anitua E, Andia I, Ardanza B, et al (2004) Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost; 91:4–15.

15 Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent; 10:225–228.

16 Weibrich G, Kleis WK, Kunz-Kostomanolakis M, et al (2001) Correlation of platelet concentration in platelet-rich plasma to the extraction method, age, sex, and platelet count of the donor. Int J Oral Maxillofac Implants; 16:693–699.

17 Barthelmai W (1969) [Isolation of thrombocytes from small blood volumes]. Klin Wochenschr; 47:266–270.

18 Meury T KLSTAM. Effect of platelet-rich-plasma on bone marrow stromal cell differentiation. [abstract]. ASBMR 26th annual meeting. 2007.

19 Cmolik BL, Spero JA, Magovern GJ, et al (1993) Redo cardiac surgery: late bleeding complications from topical thrombin-induced factor V deficiency. J Thorac Cardiovasc Surg; 105:222–227.

Sebastian Lippross, MDBiomaterials and Tissue Engineering

Program

AO Research Institute, Davos

sebastian.lippross@aofoundation.org

Mauro Alini, PhDHead of Biomaterials and Tissue

Engineering Program

AO Research Institute, Davos

mauro.alini@aofoundation.org

Summary and conclusions PRP preparation provides a

fairly simple method to deliver a variety of natural growth

factors to the patient. High concentrations of proteins acting

in concert through different pathways can be achieved by

commercially available systems that can be used in the oper-

ating room. The risks of contamination and immunogenic

response are considerably low when using FDA approved sys-

tems. The remaining risk of coagulopathies could be mini-

mized by using alternative activation methods to standard

bovine thrombin. On the whole, the beneficial effects of PRP

in clinical application remain doubtful. No appropriate clini-

cal investigations that meet all modern quality criteria have

been conducted up to now.

Based on our own and other groups’ in vitro findings, one

could hypothesize that PRP can be supportive of the healing

processes if used in the right manner. The appropriate use of

PRP has yet to be determined by larger randomized controlled

trials. Additional basic investigations on the mechanisms of

action could elucidate under which conditions PRP can act as

a tissue healing additive.

29expert zone cover theme polytrauma management

35 Hee HT, Majd ME, Holt RT, et al (2003) Do autologous growth factors enhance transforaminal lumbar interbody fusion? Eur Spine J; 12:400–407.

36 Coetzee JC, Pomeroy GC, Watts JD, et al (2005) The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. A preliminary study. Foot Ankle Int; 26:840–846.

37 Marx RE, Carlson ER, Eichstaedt RM, et al (1998) Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod; 85:638–646.

38 Mishra A, Pavelko T (2006) Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med; 34:1774–1778.

39 Driver VR, Hanft J, Fylling CP, et al (2006) Autologel Diabetic Foot Ulcer Study Group. A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers. Ostomy Wound Manage; 52:68–70, 72, 74.

40 Margolis DJ, Kantor J, Santanna J, et al (2001) Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care; 24:483–488.

20 Spero JA (1993) Bovine thrombin-induced inhibitor of factor V and bleeding risk in postoperative neurosurgical patients. Report of three cases. J Neurosurg; 78:817–820.

21 Graziani F, Ivanovski S, Cei S, et al (2006) The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts. Clin Oral Implants Res; 17:212–219.

22 Dolder JV, Mooren R, Vloon AP, et al (2006) Platelet-Rich Plasma: Quantification of Growth Factor Levels and the Effect on Growth and Differentiation of Rat Bone Marrow Cells. Tissue Eng.

23 Annunziata M, Oliva A, Buonaiuto C, et al (2005) In vitro cell-type specific biological response of human periodontally related cells to platelet-rich plasma. J Periodontal Res; 40:489–495.

24 Gruber R, Varga F, Fischer MB, et al (2002) Platelets stimulate proliferation of bone cells: involvement of platelet-derived growth factor, microparticles and membranes. Clin Oral Implants Res; 13:529–535.

25 Oprea WE, Karp JM, Hosseini MM, et al (2003) Effect of platelet releasate on bone cell migration and recruitment in vitro. J Craniofac Surg; 14:292–300.

26 Lippross S, Verrier S, Hoffmann A, et al (2007) Platelet released growth factors boost expansion of endothelial progenitor cells [abstract]. 53rd Annual Meeting of the Orthopaedic Research Society 2007; Poster No 481.

27 Ranly DM, Lohmann CH, Andreacchio D, et al (2007) Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice. J Bone Joint Surg Am; 89:139–147.

28 Pryor ME, Yang J, Polimeni G, et al (2005) Analysis of rat calvaria defects implanted with a platelet-rich plasma preparation: radiographic observations. J Periodontol; 76:1287–1292.

29 Sanchez AR, Sheridan PJ, Eckert SE, et al (2005) Regenerative potential of platelet-rich plasma added to xenogenic bone grafts in peri-implant defects: a histomorphometric analysis in dogs. J Periodontol; 76:1637–1644.

30 Rai B, Oest ME, Dupont KM, et al (2007) Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. J Biomed Mater Res A.

31 Lucarelli E, Fini M, Beccheroni A, et al (2005) Stromal stem cells and platelet-rich plasma improve bone allograft integration. Clin Orthop Relat Res; 62–68.

32 Okuda K, Tai H, Tanabe K, et al (2005) Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: a comparative controlled clinical study. J Periodontol; 76:890–898.

33 Hanna R, Trejo PM, Weltman RL (2004) Treatment of intrabony defects with bovine-derived xenograft alone and in combination with platelet-rich plasma: a randomized clinical trial. J Periodontol; 75:1668–1677.

34 Papli R, Chen S (2007) Surgical treatment of infrabony defects with autologous platelet concentrate or bioabsorbable barrier membrane: a prospective case series. J Periodontol; 78:185–193.

30 AODIALOGUE 1 | 07

Biotechnology in musculoskeletal surgery: outlook and expectations

Biotechnology represents a complex and diverse technical field

involving the fusion of modern biological methods that inno-

vate new products, capabilities and enabling technologies to

improve the quality of human life. Much argument abounds in

the literature on a single definition: each precise meaning de-

pends on field of use and context. In present economic terms,

biotechnology equates to drug innovation where modern

pharmaceutical pipelines are stocked with drug candidates

produced from biotechnology methods. But those same tech-

nologies are driving many other biomedical opportunities,

some relevant to musculoskeletal repair. A previous AO Dia-

logue article [1] and recent AO series book chapter [2] intro-

duced some general features of biotechnology use in medicine.

Most biotechnology strategies applicable to medicine are fo-

cused on new drug products from biotechnologies (eg, thera-

peutic peptides, proteins, and transgenes), incorporation of

these bioactive agents into delivery systems (carriers, coatings,

matrices), products of biotechnology (recombinant fibrin

glues, collagens, viral vectors, bio-engineered polysaccha-

rides), use of altered living cells as producers of therapeutic

agents or functional tissue replacements either in vitro (biore-

actors) or in vivo (cell therapy, regenerative medicine). Fur-

ther, active cells, therapeutic bio-derived compounds and bio-

materials are combined implant biomaterials (tissue engineered

constructs as cartilage and bone substitutes), and hybrid cell/

protein and chemical reporting constructs are exploited as ad-

vanced imaging tools (molecular beacons, genetically altered

cell probes, targeted molecular imaging agents). As capabilities

and creativity are unbridled, medicinal possibilities and surgi-

cal applications for these materials will only expand [3]. Meth-

ods in tissue engineering use many forms of biotechnology—

combining growth factors or other cell signaling molecules,

biomaterials scaffolds to provide form and support, seeded vi-

able cell populations to enable tissue regeneration, and appro-

priate bioreactors that promote recapitulation of viable tissue

form and function for novel implantable constructs. The ap-

proach is rapidly merging with regenerative medicine, often

used synonymously to signify the unified goal and strategy for

reproducing lost tissue or physiological functions with thera-

peutic and clinical potential. Bone and cartilage are primary

foci for biotechnology research, attempting to improve func-

tional tissue healing and neogenesis with varying degrees of

clinical success and failure.

From an academic perspective, biotechnology represents a

“blue sky” field: rapid advances have been made since the 1985

Nobel Prize was awarded for the polymerase chain reaction

and “recombinant” became routinely used in the Wall Street

Journal. The 21st century has been coined the “Century for

Biology” reflecting expectations of what diverse biotechnolo-

gy contributions might promise for therapeutic breakthroughs.

Nonetheless, the gap between preclinical research and clini-

cal applications is substantial. Many current biotechnology

studies provide ambivalent or starkly contrasting musculosk-

eletal outcomes. The lack of mechanistic details in many

‘cocktail’ approaches to treating difficult trauma situations

with mixtures of cells, genes, proteins, and biomaterials re-

flects the quite typical development of a complex field seeking

David W Grainger

31expert zone cover theme polytrauma management

simple solutions without many driving hypotheses. A con-

founding, dizzying array of biotech opportunities exist for

new approaches to trauma treatments, but many without sub-

stantial scientific validation to date. However, research prog-

ress must move from the current ‘black box’ and ‘blue sky’

endeavors to actually place significant tools in the hands of

clinicians. Table 1 highlights many possible areas where im-

pacting contributions are expected from preclinical to clinical

use. Several prospects and prognostications are reviewed

briefly below in some relevant areas.

1

Osteoporosis and fragility fractures. Anticipated biotechnology con-

tributions: advanced imaging, new interventional therapies, pro-

phylaxis.

Imaging New noninvasive imaging tools rely on new re-

agents with target-specific sensitivity and fidelity to provide

molecular and cellular level details. Molecular targeting and

imaging reagents are now combined with new optoelectronic

tools to improve lesion and tissue-specific contrast. Research

animals that express fluorescent proteins (GFP) in their cells

either constitutively, locally, or upon introduction of an exog-

enous cue are widely available. Hybrid molecular probes con-

taining both tissue specific agents and contrast agents that pro-

vide disease-specific activation via site-specific enzymatic

cleavage or targeting unfolding reactions have been developed.

Fiber-optic based tissue imaging is desirable using far red and

near-infrared (IR) light that travels through tissues most effi-

ciently and thus often used for whole animal imaging. How-

ever, IR-active tissue probes for such systems are rare. Now,

protease-activatable IR-active imaging probes can reveal in

vivo cathepsin B enzyme activity specific to tumor sites and

this strategy should be extended to musculoskeletal tissue en-

zymes as well. Harvested autologous bone marrow cells can

also be retrovirally transduced to constitutively express

flourescent/luminescent fusion proteins and reintroduced to

the rat. Over 4 weeks posttransplantation, the whole body dis-

tribution of transduced rat cells has been monitored using

Biotechnology target Expectations

Improved in vivo models for preclinical

evaluations

Genetically altered small and large experimental animal models that more accurately

reproduce aspects of human physiology, disease, and healing

New bioreactor-based ex vivo/in vitro living

tissue equivalents and tissue phantoms

Reduced cost, more accessible living and non-living biomimetic models for testing

therapeutic manipulations of tissue and avoid animal use

Advanced patient diagnostics and rapid

genetic analysis

Rapid, molecular level diagnosis and biomarker profiling of bone and connective tissue

disease states and risks, prediction of optimal drug therapies (pharmacogenomics)

and outcomes

Treatment of osteoporosis and fragility

fractures

Advanced molecular imaging tools, improved diagnostic and screening reagents and

methods, new interventional therapies from innovative biopharmaceutical drugs and

new devices, improved patient identification and prophylaxis

Improved cell and molecular biology

tools, methods and probes to advance

musculoskeletal research

Improved understanding of the biological basis of healing, identification of markers of

disease, genetically programmed cell types for therapies, exploitation of pluripotent

cells to program wound healing and bone neogenesis, cells as advanced imaging tools

Solutions to large bone defects, nonunions,

enhanced bone healing

Therapeutic gene and bioengineered growth factor delivery, tissue-engineered bone

regeneration, cell-based healing, reliable therapeutic vasculogenesis and new small-

molecule bone regenerative drugs

Mitigating infection Elucidation of pathogenesis mechanisms associated with implant-centered infection,

new anti-microbials addressing virulence and resistance mechanisms, new methods

to better deliver antimicrobials to implant sites, novel combination device and

biomaterials-based approaches to limit device and wound-site colonization

Reduce health care costs Depends upon regulatory and reimbursement strategies that provide economic

incentives, drive competition, and increase treatment options

Table 1 Anticipated biotechnology impacts on research, preclinical and clinical components of musculoskeletal repair.

32 AODIALOGUE 1 | 07

noninvasive bioluminescence imaging. Further novel molec-

ular and cellular homing agents, combinations with nano-

phased contrast agents (eg, particles) and associated instru-

ment innovation will continue to improve both resolution and

site-specificity in bone, cartilage, and connective tissue.

New drug targets Molecular and cellular studies reveal that

osteoblasts produce a protein signaling molecule—macro-

phage colony-stimulating factor—that induces macrophage

proliferation. A second osteoblast protein, RANKL, also binds

to a different macrophage receptor, inducing differentiation

into osteoclasts. A third osteoblast protein—osteoproteger-

in—blocks osteoclast formation by binding RANKL and

blocking its receptor interaction on macrophages. Parenteral

delivery of recombinant osteoprotegerin, a fragment of the

TNF receptor family protein (also called OCIF), to limit osteo-

clast formation, is a new therapeutic approach, reducing rates

of bone resorption by at least 60% in humans. Other molecu-

lar blockades against RANKL, such as recombinant antibod-

ies, are being developed with this capacity. Several other

known molecules in signaling pathways controlling bone for-

mation and resorption—including estrogen, parathyroid hor-

mone (PTH), and insulin-like growth factor-1 (IGF-1)—have

biotechnology development histories. Estrogen’s known nu-

clear transcriptional DNA regulation is also accompanied by

distinct osteoblast kinase-coupled receptor binding in bone

that prompts increased osteoprotegerin and reduced RANKL

production, suppressing osteoclast formation. Estrogen ex-

tends osteoblast survival while simultaneously inducing os-

teoclast death. Reduced estrogen levels accompanying meno-

pause decrease this inhibition of osteoclast formation and

resorptive activity, as well as bone building activity. PTH be-

haves in the opposite way by regulating RANKL and osteo-

protegerin to trigger osteoclast formation indirectly by bind-

ing to osteoblasts and prompting them to increase RANKL

and decrease osteoprotegerin production, respectively. De-

spite this resorptive action, the recombinant PTH fragment

(Forteo™, approved 2002, Eli Lilly) represents the first effica-

cious bone-building drug. Endogneous PTH at continuously

elevated levels over long periods promotes bone resorption;

periodic intermittent PTH injections build bone (known since

1928 from bone density studies in dogs but ignored for 50

years) by promoting osteoblast maturation and lengthening

osteoblast lifespan, enhancing numbers of bone-forming os-

teoblasts that function longer. In both men and postmeno-

pausal women, intermittently administered PTH increases

bone density (notably in spine), enhances bone structural in-

tegrity, and prevents fractures. Daily PTH injections increase

bone density 8–10% after one year, reducing fracture risk by

60%.

Wide differences in human serum IGF-1 levels, genetically

programmed but related in part to PTH levels, have important

implications for bone density and fracture incidence. IGF-I

normally circulates as a complex with the BP3 binding pro-

tein; appreciable free IGF-I is not normally found in blood and

is rapidly cleared from circulation. Administration of free

IGF-I at potentially therapeutic doses exerts acute insulin-like

side effects and lower doses exhibit limited, transient efficacy.

Somatokine™ (Insmed) is the biotechnology-derived recom-

binant equivalent of IGF-1 complexed with BP-3 in a single

molecule, studied for bone mass enhancement. Other, im-

proved biopharmaceuticals will likely result from biotechno-

logical discoveries regarding osteoporosis at the genetic, mo-

lecular and cellular levels, providing new therapeutic targets.

2

Bone defects, nonunions, enhanced bone healing. Anticipated bio-

technology contributions: gene-based and engineered growth factor

delivery, tissue engineered bone regeneration, cell-based healing,

therapeutic vasculogenesis, and bone regenerative therapies.

Biopharmaceutical therapies Similar to osteoporosis, new

biotechnologically derived drugs are sought to augment natu-

ral healing, accelerate bone formation and produce clinically

relevant amounts of new bone in areas of damaged or diseased

skeletal tissue. Many more protein-based drugs for bone neo-

genesis, primarily recombinant growth factors (eg, cytokines

and chemokines), have been reported than can be mentioned

here. Notably, the TGF-b superfamily of bone morphogenetic

proteins (BMPs) is the most studied and the most lucrative

clinical products to date. Recombinant human BMP-2

(rhBMP2, as InFuse™, Medtronics) enjoys a substantial in-

vestigative base and clinical use, mostly off-label. Many BMPs

have shown comprehensive bone inductive properties when

delivered locally either as the pure recombinant protein, or as

a transgene plasmid [4, 5]. Efficacy varies based on animal

model, patient age and health, wound site biology, and dosing.

Platelet derived growth factor (PDGF-BB) has produced prom-

ising results in several bone healing scenarios and appears

promising as another bone-targeted cytokine therapy. Two

primary limitations are evident in these cytokine delivery

strategies: (1) that a single growth factor is necessary but pos-

sibly not 100% sufficient to fully, reliably recapitulate rapid

bone regrowth, and (2) that direct delivery of the protein

agent to the wound site can often be dose and activity limit-

ing, with site-dependent efficacy. Multiple growth factor de-

livery is intuitive since this is precisely how cell-mediated

healing functions in vivo. However, multiple agent delivery to

bone sites lacks design parameters: sequential timing and dos-

ing of these endogenous agents in bone healing sites in vivo is

unknown and therefore rational duplication is impossible.

Nonetheless, several combination growth factor therapies

have been reported for bone formation [6, 7]. Delivery of the

33

therapeutic transgene for each cytokine (eg, BMP2, VEGF, or

PDGF) avoids limitations of direct protein drug delivery [8, 9].

However, control features on therapeutic gene expression (on/

off), duration, and dosing are currently problematic for reli-

able routine use. Delivery of multiple transgenes might better

duplicate endogenous BMP and cytokine synergies in vivo

[10]. Additionally, viral vectors, while extremely efficient for

transgene delivery to cells, are accompanied by serious risks of

immune reactions. Naked plasmids and nonviral gene deliv-

ery vectors are being studied as alternative gene delivery strat-

egies to bone, some with creative wound-healing responsive

designs [11], but are plagued generally by poor delivery effi-

ciencies in vivo and cell toxicity in some cases [12]. Future

biotechnology improvements are critical: new innovative

viral vector modifications to reduce local dose requirements

and host response, more effective nonviral vectors for local

gene delivery, and bioengineered cells (eg, ex vivo modified

stem cells) with introduced therapeutic cytokine genes tar-

geted to injury sites upon injection. New drug conjugates, re-

combinant protein signal molecules, and small molecule sur-

rogates with therapeutic mitogenic or morphogenic properties

in musculoskeletal repair are inevitable.

Cell-based approaches Many osteo-inductive biomaterials

have been described but their almost uniform disappointing

clinical performance to date is notable. Most notable recent

innovation in this area involves biomaterials scaffolds en-

hanced with biotechnology: tissue-engineered implantable

constructs capable of reproducing tissue form and function

using viable cells and potent drug combinations [13, 14]. To

improve in vivo performance, integrated understanding of in-

trinsic biological factors and kinetics governing bone and tis-

sue development in vivo, and their appropriate therapeutic

exploitation and functional control in situ are essential. Tis-

sue engineering methods are now inseparable from modern

pharmaceutics in using materials science, cellular and mo-

lecular biology to identify therapeutic targets, produce bioac-

tive substances and deliver them specifically to tissue sites to

promote specific biological responses. Most therapeutically

important neotissues will require production of transport-

competent organized vascular and neural networks for sur-

vival. Defect neovasculogenesis remains an unsolved prob-

lem: nothing regenerates without adequate perfusion. This is

limiting production of three-dimensional implants without

cell necrosis and viability issues. Numbers of requisite endo-

expert zone

34 AODIALOGUE 1 | 07

thelial progenitor cells vary enormously across species mak-

ing cross-comparisons difficult. The capability of angiopotent

cell types to adequately and rapidly restore perfusion to defect

sites to enable normal healing remains to be seen. Intraopera-

tive solutions to this problem are difficult. Biotechnological

enhancements of conventional scaffold approaches to bone

induction and regeneration require further work to distin-

guish themselves as reliable alternatives. It appears that sim-

ply mixing all biological components or primordial tissue into

a porous biomaterial and implanting it into a wound site is

insufficient in most cases to produce the desired clinical end-

point. That is, being present is not functionally equivalent to

timing and dosing of endogenous presentation.

Progenitor cell-based strategies represent an area of current

excitement and promise. Stem cell therapies are certainly po-

litically and scientifically dominant, but mesenchymal stem

cells in particular, with their capacity to differentiate to osteo-

blast, chondrocyte, fibroblast, and adipocyte cells, have at-

tracted substantial orthopedic and trauma attention [15, 16].

MSCs vary in their regenerative capacity, but have been used

successfully in human bone repair [17]. Identification of fac-

tors and pathways that promote reliable MSC osteogenic com-

mitment and allow use of MSCs with functional potential for

optimal bone repair remains a critical challenge. Age and

source-related regenerative variability are also important is-

sues. Bone-healing acceleration in response to osteogenic fac-

tors appears to result from increased recruitment in respon-

sive MSCs from the soft-tissue compartment around the bone

site, specifically sourced from muscle, fascia, vasculature, and

nerves (ie, cell recruitment and differentiation). Lastly, the

distinct roles of local biomechanical stimuli versus the intrin-

sic MSC mitogenic and morphogenic potential of the bone

healing site remain to be distinguished and exploited in mus-

culoskeletal healing scenarios. MSC coordination of vasculo-

genesis could be mechanically cued [18]. In these contexts,

further MSC genomic and proteomic analyses should help

identify molecules and mechanisms that promote reliable,

sustained osteogenic MSC mitogenic and morphogenic poten-

tial.

3

Infection. Anticipated biotechnology contributions: elucidation of

pathogenesis mechanisms associated with implant-centered infec-

tion, new antimicrobials, new methods to deliver antimicrobials to

implant sites, novel combination device and biomaterials-based ap-

proaches to limit device colonization.

Infection risk in an antibiotic-resistant era is a continuing

concern, and increasing implant incidence increases that risk

of infection [19, 20]. Modern pathology and infectious disease

research has been aided immensely by biotechnology meth-

ods. Model pathogen knock-outs, recombinant assay reagents,

and microbial genetic profiling provide enormous amounts of

new information about infection and disease, antibiotic resis-

tance mechanisms, and potential new antimicrobial targets.

This is now applied to device-centered infection problems and

elucidation of new antibiotics. Traditional synthesis of natural

antibiotics is often tedious, sometimes impossible or uneco-

nomical. Biotechnology methods permit fermentation of ge-

netically engineered microbial cultures to mass-produce com-

plex natural products and drug libraries beyond current reach

of organic chemists. Additionally, new antimicrobial bioma-

terials strategies to limit adherence and colonization, inacti-

vate pathogenic phenotypes (eg, by confounding microbial

quorum sensing), and locally deliver new antimicrobials more

effectively will emerge from biotechnology contributions to

this area. Infection prevention is much more effective than

post facto attempts to eliminate it, so that prophylaxis is more

attractive in new antiinfectives.

Other considerations for biotechnology Two further issues

cloud the horizon for clinical adoption of biotechnology: in-

surance reimbursement and regulatory strategies. Regardless

of research promise or clinical efficacy, these two hurdles rep-

resent rate-limiting steps to introducing experimental tech-

nology to the population at large. Reimbursement policies de-

termine to a large extent whether any medical innovation is

readily adopted by clinicians, and, importantly, whether bio-

technology firms (and their stockholders) can risk investment

into product development and innovation [21]. Regulatory

policies differ widely in biotechnology across countries and

continents [22]. Transparent, uniform processes are currently

lacking. The United States in particular faces a landmark deci-

sion in 2007 about regulating so-called bio-generics—phar-

maceuticals of biotechnology origin coming off patent. This

policy will dictate to a large extent financial requirements for

bringing new biotechnology products through the approval

path to market, and how future products will be developed

and innovated with this model, and in what specific clinical

areas [23]. Cell therapy products in particular remain an out-

standing example of research intrigue and promise, and regu-

latory doubt: such therapies might not offer product designs

for wide clinical adoption that can pass through regulatory

requirements with sufficient market economics to provide in-

centive for their development [24, 25].

Acknowledgements: The author thanks the many colleagues

who have imparted valuable perspectives, wisdom, and in-

sight. The field is far too big to go at it alone.

35expert zone cover theme polytrauma management

David W Grainger, PhDMember, AO AcC, BAB

Inaugural George S & Dolores Doré Eccles Presidential Endowed Chair of

Pharmaceutics and Pharmaceutical Chemistry, and Professor of Bioengineering

Departments of Pharmaceutics and Pharmaceutical Chemistry, and Bioengineering

University of Utah, Salt Lake City, USA

david.grainger@utah.edu

Bibliography

1 Grainger DW (2006) Update on AO-sponsored research in biotechnology. AO Dialogue; 1:34–37.

2 von Rechenberg B, Meinel L, Grainger DW, et al (2006) Introduction to biotechnology. Rüedi TP, Buckley RE, Moran CG (eds) AO Principles of Fracture Management. 2nd ed. Stuttgart New York: Thieme Verlag.

3 Gurtner GC, Callaghan MJ, Longaker MT (2007) Progress and potential for regenerative medicine. Ann Rev Med; 58:299–312.

4 Einhorn TA (2003) Clinical applications of recombinant human BMPs: early experience and future development. J Bone Joint Surg Am; 85(90003):82–88.

5 Seeherman H, Wozney JM (2005) Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev; 16(3):329–345.

6 Chen RR, Mooney DJ (2003) Polymeric growth factor delivery strategies for tissue engineering. Pharm Res; 20:1103–1112.

7 Puleo DA (2003) Biotherapeutics in orthopedic medicine. Drug Develop; 17:301–314.

8 Jang J-H, Houchin TL, Shea LD (2004) Gene delivery from polymer scaffolds for tissue engineering. Exp Rev Med Dev; 1:127–138.

9 Musgrave DS, Bosch P, Ghivizzani S, et al (1999) Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone; 24(6):541–547.

10 Franceschi RT, Yang S, Rutherford RB, et al (2004) Gene therapy approaches for bone regeneration. Cells Tissues Organs; 176:95–108.

11 Schmoekel HG, Weber FE, Schense JC, et al (2005) Bone repair with a form of BMP-2 engineered for incorporation into fibrin cell ingrowth matrices. Biotechnol Bioeng; 89:253–262.

12 Partridge KA, Oreffo RO (2004) Gene delivery in bone tissue engineering; progress and prospects using viral and non-viral strategies. Tissue Engineering; 10:295–307.

13 Davies JE (2001) Bone Engineering. EM Squared, Inc.: Toronto.14 Mistry AS, Mikos AG (2005) Tissue engineering strategies for bone

regeneration. Regenerative Medicine II, Yannas IV (ed), Adv Biochem Eng Biotechnol series; 94:1–22.

15 Caplan AI (2005) Mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Engineering; 11(7–8):1198–1211.

16 Rahaman MN, Mao JJ (2005) Stem cell-based composite tissue constructs for regenerative medicine. Biotechnol Bioeng; 91(3):261–284.

17 Quarto R, Mastrogiacomo M, Cancedda R, et al (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. NEJM; 344:385–386.

18 Kasper G, Dankert N, Tuischer J, et al (2007) Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells; 25:903–910.

19 Darouiche RO (2004) Treatment of infections associated with surgical implants. N Engl J Med; 350(14):1422−1429.

20 Harris LG, Richards RG (2006) Staphylococci and implant surfaces: a review. Injury; 37(Suppl 2):S3–14.

21 Phillips KA (2006) The intersection of biotechnology and pharmacogenomics: health policy implications. Health Affairs; 25:1271–1280.

22. Patterson LA (1999) A Comparison of biotechnology regulatory policy in the United States and the European Union. In the European Union Studies Association (EUSA) Biennial Conference 1999 (6th); Pittsburgh, PA, USA.

23 Swanson RA (1986) Entrepreneurship and innovation: biotechnology. In The Positive Sum Strategy: Harnessing Technology for Economic Growth; National Academy Press, Washington, DC, USA.

24 Daniels JT, Secker GA, Shortt AJ et al (2006) Stem cell therapy delivery: treading the regulatory tightrope. Regen Med; 1:715–719.

25 Halme DG, Kessler DA (2006) Regulation of stem-cell–based therapies. New Engl J Med; 355:1730–1735.

36 AODIALOGUE 1 | 07

Pelvic and acetabular fracturesPast, present, and future

Introduction This article is a written summary of the Marvin

Tile 2006 Lecture given by Martin Bircher. The Marvin Tile

Lecture is given at the University of Toronto Pelvic and Ace-

tabular Fracture course to recognize Marvin Tile for his out-

standing contributions to orthopedic surgical teaching and in

particular his commitments to pelvic and acetabular fracture

treatment. In 1987, Mr Bircher was a Marvin Tile fellow when

his passion for trauma management and treatment of pelvic

and acetabular injuries was ignited. Mr Bircher returned to

London, England, where he put his passion into action, be-

coming one of the most respected pelvic and acetabular frac-

ture surgeons in the United Kingdom. This paper entitled

“Pelvic and acetabular fractures—past, present, and future”,

provides us with an overview of where we have come from so

as to aid in planning for the future.

The past In ancient China and Egypt there is abundant evi-

dence for the treatment of orthopedic injuries including frac-

tures of the pelvis. Mummified bodies have been found with

overlapping of the pubic symphysis [1]. These may have been

caused by some unpleasant injury, perhaps crushed by large

stones being used to construct pyramids. However it is more

likely that these deformities were caused by the process of

mummification and bandaging itself. Perhaps overzealous

pelvic sheeting!

In India, surgery was developing with instruments devised to

release ligaments, and traction apparatus to reduce disloca-

tions of the hip. In Ancient Greece there are descriptions of

wounds about the pelvis being caused by arrows, and pelvic

and acetabular fractures being caused by heavy stones.

Hippocrates actually classified hip dislocation [2]. He de-

scribed inward, outward, backward, and forward dislocations

of the head of the femur in relation to the pelvis. He devised

strategies for relocation, emphasizing the importance of a dif-

ferent technique for each different type of dislocation.

Around the time of the birth of Christ, anatomy became of

great interest. Accident surgery had also become very impor-

tant. Avicenna (980–1087 AD) produced many texts in Arabic

describing anatomical structures and he again emphasized

the underlying principles of fracture treatment outlined by

Hippocrates [3].

In 1066, William the Conqueror arrived in England and de-

feated King Harold at the Battle of Hastings. William was a

warrior who had no interest in medicine and spent his years

pacifying the unruly British. It is widely reported that Wil-

liam the Conqueror died of a ruptured testicle but I believe he

actually died of the complications of a pelvic injury. Although

a ruptured testicle would be acutely painful, it will not in it-

self lead to death. I believe the sequence of events were as fol-

lows: William’s wife became increasingly irritated by his en-

larging frame. In 1087, she sent him to Rouen to go on a diet.

On the way he was involved in a skirmish (he could not really

resist a fight). In those days saddles had a very high pommel

and as his horse stumbled he was thrown against the pommel

Martin Bircher

37expert zone cover theme polytrauma management

and sustained a symphyseal separation. I often see these in

modern day horse riders, particularly in North America where

saddles are of a slightly different design than in Europe. This

would account for his external injuries which I think were

misinterpreted as a testicular rupture. I believe he sustained a

symphyseal separation and injury to the genito-urinary tract,

probably a urethral rupture. There would have been second-

ary contamination leading to septicemia and death.

During the Dark Ages, Europe saw very few ad-

vances in the specialty of orthopedics and in par-

ticular pelvic surgery. The modern specialty was

really born with the publication of Malgaigne’s

books on fractures and subluxations in 1847 [4].

At the same time in the United Kingdom, Sir

Astley Cooper (1768–1841) described various

pelvic fractures, making the distinction between

marginal stable fractures and unstable pelvic

ring injuries. At this stage it should be empha-

sized that all these observations were made on

clinical grounds with no x-rays. For an acute di-

agnosis to be made there had to be obvious visi-

ble or palpable displacement of bones. This is

why in Malgaigne’s books and atlas he only de-

scribes significantly displaced fractures and dis-

locations of the pelvis. There is some confusion

with modern day surgeons about what precisely

a Malgaigne fracture is. I believe if one studies

his books closely, he is describing what is now known as bilat-

eral sacral fracture or “jumper’s fracture”. These are the H-

shaped double vertical shear fractures that people sustain

when they fall or jump from a great height. There are usually

saggital transforaminal fractures of the sacrum accompanied

by transverse connections with translocation of the sacrum

and encroachment of the sacral canal. These injuries are usu-

ally complicated by neurological damage. Malgaigne describes

these fractures associated with people jumping from build-

ings that were on fire. He also describes novel techniques for

reduction of the fractures with the introduction of large

wooden rods into the rectum. The wooden rod would reduce

the translated sacral fractures into a better position. However,

the technique was usually complicated by gross abdominal

distension and he therefore went on to devise silver cylinders

with cannulas to allow the escape of air. He records one pa-

tient being able to walk home after such treatment after twelve

days despite “a little infection”! The modern specialty of ace-

tabular surgery was yet to be born.

With the introduction of x-rays, the subspecialty advanced

rapidly and different types of pelvic and acetabular fracture

were identified. Albin Lambotte (1866–1955) produced stun-

ning descriptions of techniques for fixing sacral fractures and

described the use of sacral bars [5]. He was truly the master of

all surgeries and significantly advanced the surgery of fracture

management. In the UK in 1948, Sir Frank Holdsworth (1904–

1969) produced his paper on dislocations and fracture disloca-

tions of the pelvis [6]. He was a student at Cambridge and St

George’s Hospital, Hyde Park. He undertook a number of ju-

nior positions at St George’s before becoming the first orthope-

dic specialist in Sheffield in 1937. His paper studied 50 patients

and made key observations—including the dangers of death by

bleeding and the complication of genitor-urinary injury. He

concluded that sacral iliac dislocation was an evil injury with

most patients suffering chronic permanent agonizing pain

whereas patients with ilio-sacral fracture dislocations (cres-

cent fractures) had a better overall outcome.

In the 1950s and 1960s, other than pelvic slings, the only sur-

gical treatment recommended for unstable pelvic injuries were

forms of external fixation. These became the gold standard

treatment of such injuries. George Pennal (1913–1976) work-

ing in the University of Toronto Anatomy Department, began

to identify subsets of pelvic fractures including lateral com-

pression injuries, vertical shear forces, and open book type

fractures. The study of the biomechanics led him to produce a

classification which was later further modified by Tile.

Meanwhile in Paris in the late 1950s and 1960s, Robert Judet

began attempting to treat displaced acetabular fractures sur-

gically. He felt that the outcomes with displaced acetabular

fractures following conservative treatment were unaccept-

able. He identified certain subsets of acetabular fractures that

did not do well with conservative treatment. These included

fractures that involved the tectum or roof and those fractures

where the hip was unstable. He described ten classic fracture

patterns (five basic and five complex). Judet also developed

38 AODIALOGUE 1 | 07

many surgical approaches, particularly the ilio-inguinal ap-

proach, for treatment of anterior acetabular injuries. His work

was continued by his student Emile Letournel who diligently

collected data, listed complications, and educated a large

group of surgeons including Claude Martinbeau, Joel Matta,

Geoffrey Mast, Keith Mayo, and Eric Johnson. Other sur-

geons visited Paris regularly, including David Helfet and Roy

Moed. Meanwhile in Toronto, Marvin Tile continuing Pen-

nal’s work, published the classification of pelvic fractures in

the Journal of Bone & Joint Surgery (1986), and brought the

specialty together with his comprehensive book entitled

“Fractures of the Pelvis and Acetabulum”. There have now

been three editions of Tile’s book (1984, 1995, and 2003).

With Tile’s teaching and the Sunnybrook fellowships, the

practice of pelvic and acetabular surgery has been advanced

and spread across the world. I was fortunate enough to be one

of his fellows in 1987. His books complement the equally bril-

liant text on fractures of the acetabulum produced by Emile

Letournel.

The present Presently in the developed world, a full time job

as a trauma surgeon is not considered compatible with a good

lifestyle. The hours can be inconvenient and other subspecial-

ties within orthopedics pay much more handsomely. For pel-

vic and acetabular fracture surgery to provide the greatest

benefit to the injured patient in all countries, certain issues

need to be urgently addressed. By providing a good pelvic

fracture service the trauma system as a whole will benefit.

Trauma hospitals are struggling financially and this is at least

partly due to the unsophisticated coded systems that are used

to define activity and thus funding. For example, there are

over 17 different ICD10 codes for pelvic fractures and over 40

codes relevant to the pelvis in the OPCS system. Better coding

systems need to be developed in order to allow prompt pay-

ment for the treatment of trauma patients.

However, some units, particularly within the USA, are avoid-

ing treating uninsured trauma patients as they drain resourc-

es. This is known in the United States as ‘dumping’. These is-

sues are not only causing clinical problems but also have a

major detrimental effect on training.

An example of these inefficiencies was highlighted in the

United Kingdom in 2002. After a frustrating year of delays in

the definitive treatment of pelvic and acetabular patients I

went public with an audit that demonstrated that, within my

locality, it was 12 days between injury and a definitive surgery

for a pelvic and acetabular fracture. This audit led to a number

of meetings with healthcare providers resulting in the intro-

duction of a special tariff for definitive pelvic and acetabular

fracture reconstruction. It was felt that if there was a better

financing capability, the delay would be reduced. This in some

ways helped the situation as trauma units started receiving

more money for the treatment of pelvic fractures. However

other injuries eg, open fractures, are still poorly resourced

and the trauma units are still struggling. Unfortunately a sub-

sequent audit in my unit between June 2004 and June 2005

showed that the mean delay between injury and definitive

surgery still remains 12.6 days. The steady increase in local

trauma that remains underfunded has absorbed the extra re-

source earmarked for pelvic fractures. Other meetings are

going on in order to try and further rectify this problem. These

problems I believe are mirrored across Europe and North

America.

What are the solutions? We must make trauma care attrac-

tive as a career to recruit young doctors, make sure they are

paid appropriately, and that they have good working condi-

tions. We need to apply political pressure and lobby our po-

litical masters.

39expert zone cover theme polytrauma management

There is some good news, certainly within the UK. We have

over a dozen specialist pelvic units with fellowship trained

surgeons. The new tariff will help to fund these units. Regular

courses are run across the world and we recently completed

another successful course in September 2006. The bad news is

that these unacceptable delays remain and the pelvic story is

somewhat deflected away from the fact that trauma systems

are failing across the world. We are also being flooded with an

increasing number of osteoporotic traumas associated with

our ageing population.

We need to collect data. With this in mind, the European Pel-

vic Association of Surgeons (EPAS) has been formed. This will

give us teeth. We also need to evolve better coding systems

and continue educating ourselves, the public, and the politi-

cians.

The future The immediate future of pelvic and acetabular

surgery, in my opinion, should mainly focus on organization-

al changes. Systems need to be defined. Education needs to

continue. Trauma, and particularly pelvic and acetabular sur-

gery, needs to be brought to the forefront and inadequacies of

our systems need to be highlighted to the politicians and the

public. We should continue developing fine instruments and

strive to develop new techniques to make the surgery of pelvic

and acetabular fractures safer. With this in mind, computers

will come to the forefront. Image guided surgery combined

with sophisticated preoperative imaging will allow more fo-

cused treatment and less extensive incisions which are associ-

ated with a high complication rate. These advances, however,

will not be possible if cases are delayed and callus forms

around fracture surfaces. Indirect reductions are impossible

under these circumstances. It would be an advantage to have

new gadgets eg, talking drills that tell you the length of the

screw, self-tapping biodegradable implants, precontoured

plates, fracture glue, and some form of bone restorer.

We need to link up with our hip revision surgical colleagues

to deal with this influx of osteoporotic acetabular trauma. In

the acute phase, reconstruction is sometimes impossible or

fruitless. It is now recognized that techniques, other than re-

construction, are available and are indicated when fractures

are very comminuted or bone quality is poor. Within our unit

at St George’s, there is close liaison between the fracture group

and the hip reconstruction revision group.

In the more distant future, robotic surgery may become a pos-

sibility. On the biological front, there is encouraging work on

cartilage replacement and nerve regeneration. We are still

confronted on a regular basis with young patients with large

areas of primary articular cartilage damage occurring at the

time of an acetabular injury. Primary articular cartilage loss is

irreversible and until we have a system of replacing it, we will

not achieve good long term outcomes following a reconstruc-

tion of such injuries. One of the more devastating complica-

tions following a pelvic fracture is lumbo-sacral nerve injury.

Young men are rendered impotent and women suffer neuro-

logical pelvic floor symptoms. In the future we may be able to

replace areas of injured nerve thus reversing neurological

damage, impotence, and pelvic floor weakness.

In the more distant future spare part surgery may become an

option. New acetabular sockets may be available and perhaps

whole sacral units with nerves attached may be pulled “off the

shelf”.

If one looks at a UK £2 coin you will see written around the

edge the saying “standing on the shoulders of giants”. Our un-

derstanding and advancement of pelvic and acetabular sur-

gery relies on the work of our forefathers. I am privileged to

have stood on the shoulders of Marvin Tile and will always be

grateful for the teaching and advice he has given me.

Bibliography

1 Wenz W, et al (1975) Blick in die Vergangenheit. “Ägyptische Mumie im Röntgenlicht”. Adiologe; 125: 45–49.

2 Lithington ET (1828) Hippocrates. London. Loeb classic library Vol III.3 Varusis Amidas (2001) History of Orthopaedics. Athens.4 Malgaigne JF (1847) Traite des fractures et des luxations,

2 volumes.5 Lambotte A (1913) Chirurgie Oreratoire du Fractures. Paris,

Masson et Cie.6 Holdsworth FW (1948) “Dislocations and Fracture Dislocations of

the Pelvis”. J Bone Joint Surg Br; 30:461.

Martin Bircher, MDUnited Kingdom

linda.haylor@stgeorges.nhs.uk

40 AODIALOGUE 1 | 07

AO DebateAcute on chronic, unstable slipped capital femoral epiphysis

Steven L Frick and Virginia Casey

Acute on chronic, unstable slipped capital femoral epiphysis is

a common condition that faces the orthopedic surgeon in the

emergency department or the clinic. For many years, either in

situ pinning or gentle closed reduction and in situ pinning has

been recommended. Recently, with a newer understanding of

the hip blood supply and the concept of femoral acetabular

impingement as a cause for osteoarthritis, interest in the pos-

sibility of open reduction and pinning was renewed. This de-

bate will explore the two options.

Case presentation A 12-year-old male was presented to the

emergency department by ambulance after tripping and fall-

ing in the playground at school. He was unable to get up and

could not bear weight on his left lower extremity. He reported

3 months of left knee pain and occasional limping prior to the

fall. He had an unstable slipped capital femoral epiphysis on

the left that was completely displaced (Fig 1a–b).

What is the best surgical treatment for this patient? Is it emer-

gent or urgent? What is his risk of osteonecrosis? What is the

role of intracapsular hematoma as a possible cause of osteone-

crosis?

Steven L FrickOpen reduction for acute on chronic slipped capital femo-ral epiphysis The recommended treatment for slipped capi-

tal femoral epiphysis (SCFE) has for years been pinning in

situ, regardless of the severity of the slip, as retrospective long

term follow-up studies reported higher complications and

poorer results with reduction or realignment procedures [1].

The case presented of an acute on chronic SCFE is better dis-

cussed in terms of physeal stability, as Loder has clearly de-

fined unstable SCFE (patient unable to bear weight) as the

major risk factor for osteonecrosis (ON) [2]. The classification

based on timing of symptoms previously used in the literature

is helpful in understanding the pathoanatomy of SCFE, which

differs from femoral neck fractures as the proximal femur re-

models in response to the slip. The callus that thus forms pos-

teromedially has important treatment implications.

Traditional teaching is that reduction of SCFE is dangerous

and may cause ON. The literature is unclear if this applies to

stable slips, unstable slips, or both. Standard treatment of un-

stable SCFE frequently describes unintentional reduction

during positioning prior to internal fixation in situ, and does

not recommend a formal reduction maneuver. Practitioners

are cautioned to avoid forceful manipulations and reductions

that may cause ON. An anatomical explanation for the in-

creased risk would be stretching the posteromedial retinacu-

lar vessels over the slip callus.

Major adverse sequelae of SCFE are ON, poor motion, and

early arthritis. Chondrolysis is less common in the era of can-

nulated screw fixation. Loder reported an ON rate of 50% in

unstable slips, and other reports cite a 10–50% risk. An arte-

riographic study of 5 unstable SCFE describes loss of the dom-

inant vessel supplying the epiphysis in 3 of the 5 when the

epiphysis is displaced, and in one case demonstrated restora-

tion of flow in this vessel after reduction. The study concluded

that in some unstable slips the vascular injury occurs at the

41expert zone cover theme polytrauma management

time of injury, and that reduction does not necessarily con-

tribute to the risk of ON [3]. Growing evidence shows that

residual anatomic abnormalities predispose patients to early

hip osteoarthritis (OA)—how much deformity is acceptable,

and how much remodeling potential a given individual has

are not yet clearly defined. For SCFE, long term studies (Wein-

stein) state that deformity can be tolerated well.

The idea that reduction of an unstable SCFE is dangerous is

not supported by more recent reports. Practically, some un-

stable slips cannot be pinned in situ as the neck is completely

displaced from the epiphysis. After 40 years of experience,

two centers reported only a 13% incidence of ON following

early manipulative reduction of acute SCFE, although not all

had open procedures or capsular decompression. Gordon et al

recommend early reduction of unstable slips with arthrotomy

(decompression) and cannulated screw fixation to lessen the

risk of ON. Open reduction of unstable SCFE has been advo-

cated [4, 5], with the advantage of decompressing any intra-

capsular hematoma, and allowing some direct assessment of

reduction. The disadvantage is that closed reductions and

open anterior approaches do not allow visualization and re-

moval of posteromedial callus. This leads to the recommenda-

tion to reduce unstable slips to their “stable” or “preacute”

position—ie, to the position that will not stretch the capsular

vessels over the callus. To decrease the risk of ON, the surgeon

accepts residual deformity that may predispose the patient to

poor motion and early OA.

Ganz et al [6] have increased our knowledge and understand-

ing of the blood supply to the femoral head, and also of the

effects of proximal femoral deformity on hip joint longevity

and function, with an emphasis on femoroacetabular im-

pingement (FAI) as a cause of early OA of the hip. The detailed

studies of proximal femoral arterial anatomy [7], develop-

ment of an anatomically based surgical approach and clinical

series of safe surgical dislocation of the hip [8] offer a new way

to address SCFE. The potential adverse effect of intracapsular

hematoma on femoral head blood flow has also been con-

firmed, showing that increased intracapsular pressure can de-

crease perfusion to the epiphyseal region and may contribute

to ON following femoral neck trauma (Ng and Cole).

Leunig et al reported utilization of the Ganz surgical disloca-

tion approach for SCFE in an article that primarily described

the intraarticular changes noted in SCFE patients intraopera-

tively consistent with FAI. No patient developed ON (3 had

acute on chronic SCFE), and the research from this group has

led others to begin using the surgical dislocation approach to

address SCFE pathology, including the unstable slip. If this

approach can result in a decreased incidence of ON following

unstable SCFE, it may become the standard treatment method

as it allows restoration of normal anatomy that should also

improve motion and lessen the risk of early OA. Surgical dis-

location of the hip allows circumferential visualization of the

femoral head and neck, with the piriformis and importantly

obturator externus tendons intact to protect the vascular sup-

ply. The exposure of the femoral neck must be done with care

and must not damage the vessels within the periosteum and

capsular layer posteromedially. This exposure affords visual-

ization of the remodeling and callus along the posteromedial

femoral neck, which can then be removed to allow complete

reduction of the slip deformity without stretching the vessels

over the callus and compromising perfusion. The position of

the head on the neck can also be directly visualized, lessening

dependence on radiographic assessments of head-neck align-

ment. It still remains to be seen whether or not this approach

can eliminate ON, or if the injury to the blood supply can

occur at the time of initial displacement and be unrecover-

able.

Recent literature supports reduction of unstable SCFE and

stable fixation with decompression of any intracapsular he-

matoma. The options for achieving this are closed reduction

and fixation followed by capsulotomy, open reduction via an

anterior approach, or surgical dislocation. Follow-up studies

(>2 years) are needed to document that surgical dislocation

can be done safely in patients with unstable SCFE.

Virginia CaseyClosed reduction and in situ pinning Slipped capital femo-

ral epiphysis (SCFE) is a common disorder that affects 0.2 to

10 adolescents per 100,000. It is characterized by displace-

Fig 1a–b Unstable slipped capital femoral

epiphysis.

b

c

b c

42 AODIALOGUE 1 | 07

a

ment of the femoral head on the metaphysis causing pain and

deformity. SCFE can be classified based on duration of the

symptoms (more traditional classification) or on physeal sta-

bility as described by Loder. Classification of symptoms based

on chronicity includes acute, chronic, and acute on chronic

categories. Older literature utilized this classification for data

collection. More recent literature characterizes slips accord-

ing to physeal stability, which has been found to be the major

determinant for the risk of developing osseous necrosis.

Treatment of chronic stable SCFE is not controversial. These

patients have no risk of osseous necrosis and do well with in

situ pinning [2, 9, 10]. However, significant controversy re-

mains for the optimal treatment of a child with an unstable

SCFE (patient unable to bear weight) be it acute or acute on

chronic in nature.

There are several factors to consider when treating unstable/

acute slipped capital femoral epiphysis. The most important is

the avoidance of osseous necrosis. SCFE with osseous necrosis

is more likely to have a poor functional outcome with the

need for subsequent surgery. Factors that may be associated

with the development of osseous necrosis include physeal sta-

bility, slip severity, age of the patient, timing of fixation, num-

ber of screws/pins for fixation, and reduction of the deformity.

Of these factors, the only predictor of osseous necrosis that is

consistent in the literature is physeal instability. The literature

cites a 10–50% osseous necrosis rate in unstable SCFE.

Few studies evaluate the treatment of SCFE. The papers that

do assess treatment are limited by small patient numbers, ret-

rospective designs, and significant treatment variability.

Treatments studied include: casting, in situ pinning, inciden-

tal reduction and pinning, formal closed reduction, pinning

with or without preoperative traction, and open reduction

with or without a number of different femoral osteotomies.

The most common treatments cited in a recent survey of the

POSNA membership revealed that 84% perform in situ pin-

ning after positioning or incidental reduction, 11.8% pin after

a formal reduction, and 3% perform an open reduction.

Reduction that is done with positioning and is “incidental” is

thought to reduce the acute component of an acute on chron-

ic slip. This allows for some deformity correction without

stretching the blood supply over the callous which forms on

the posterior-medial femoral neck in chronic SCFE. Peterson

demonstrated no increase in incidence of osseous necrosis

with closed reduction of acute SCFE. However, Tokmakova

found an increased risk of osseous necrosis even with a partial

reduction when compared to pinning in situ.

O’Brien and Jones have shown that even in patients with

moderate to severe SCFE there is extensive remodeling of the

deformity [11]. In these patients there was resorption of the

anterolateral femoral neck allowing near normal hip range of

motion with the exception of a loss of 5–20° of internal rota-

tion in some patients. Those patients with incomplete remod-

eling are candidates for a femoral osteotomy.

The long term literature on SCFE is favorable for the hips with

mild to moderate deformity and no osseous necrosis [1]. The

hips with severe deformity have increasing hip pain with

time. Those hips with osseous necrosis tend to do poorly. Thus

treatment is aimed at decreasing rates of osseous necrosis

while minimizing deformity. The literature does not support

an obvious best treatment option for unstable SCFE. Open

treatment using the Ganz surgical dislocation approach may

prove to decrease the rates of osseous necrosis and restore nor-

mal anatomy, though this is not yet supported in the litera-

ture.

In situ pinning and incidental reduction with pinning are

percutaneous techniques that are not technically difficult.

The known long term results of these treatments are as good if

not better than open reduction techniques that are techni-

cally more challenging and not as amenable to being per-

formed by general orthopedic surgeons. While time may prove

that new open reduction techniques are successful in the pre-

vention of osseous necrosis, current literature supports the

use of less invasive techniques and should be the mainstay of

treatment for unstable SCFEs.

b

c

Fig 2a–b X-rays after 4 weeks showing no change

in alignment of the hip.

43expert zone cover theme polytrauma management

Bibliography

1 Carney BT, Weinstein SL, Noble J (1991) Long-term follow-up of slipped capital femoral epiphysis. J Bone Joint Surgery Am; 73(5):667–674.

2 Loder RT, Richards BS, Shapiro PS, et al (1993) Acute slipped capital femoral epiphysis: the importance of physeal stability. J Bone Joint Surg Am; 75:1134–1140.

3 Maeda S, Kita A, Funayama K, et al (2001) Vascular supply to slipped capital femoral epiphysis. J Pediatr Orthop; 21(5):664–667.

4 Parsch K, Zehender H, Buhl T, et al (1999) Intertrochanteric corrective osteotomy for moderate and severe chronic slipped capital femoral epiphysis. J Pediatr Orthop B; 8(3):223–230.

5 Aronson J, Tursky EA (1996) The torsional basis for slipped capital femoral epiphysis. Clin Orthop Relat Res; (322):37–42.

6 Ganz R, Parvizi J, Beck M, et al (2003) Femoroacetabular impingement: a cause for osteoarthritis of the hip. Clin Orthop Relat Res; (417):112–120.

7 Gautier E, Ganz K, Krugel N, et al (2000) Anatomy of the medial femoral circumflex artery and its surgical implications. J Bone Joint Surg Br; 82(5):679–683.

8 Beck M, Kalhor M, Leunig M, et al (2005) Hip morphology influences the pattern of damage to the acetabular cartilage: femoroace-tabular impingement as a cause of early osteoarthritis of the hip. J Bone Joint Surg Br; 87(7):1012 –1018.

9 Kennedy JG, Hresko MT, Kasser JR, et al (2001) Osteonecrosis of the femoral head associated with slipped capital femoral epiphysis. J Pediatr Orthop; 21(2):189–193.

Fig 3a–b Osteonecrosis with collapse of the

femoral epiphysis.

b

c

Outcome The patient was taken urgently to the operating

room and underwent reduction to the “preacute” position by

placing him in traction on a fracture table, under fluoroscopic

guidance. The proximal femur was stabilized with a single 7.3

mm cannulated screw, and the hip was aspirated to decom-

press the intracapsular hematoma. The patient was kept on

crutches with limited weight-bearing for 4 weeks, and x-rays

then showed no change in alignment of the hip and good posi-

tion of the screw (Fig 2a–b).

The patient was then lost to follow-up. He returned at 11

months after his surgery complaining of left groin pain and a

limp, and x-rays at that time showed osteonecrosis with col-

lapse of the femoral epiphysis (Fig 3a–b).

10 Tokmakova KP, Stanton RP, Mason DE (2003) Factors influencing the development of osteonecrosis in patients treated for slipped capital femoral epiphysis. J Bone Joint Surg; 85-A(5):798–801.

11 O’Brien ET, Fahey JJ (1997) Remodeling of the femoral neck after in situ pinning for slipped capital femoral epiphysis. J Bone Joint Surgery Am; 59(1):62–68.

Suggestions for further reading

Aronsson DD, Loder RT (1996) Treatment of the unstable (acute) slipped capital femoral epiphysis. Clin Orthop Relat Res; (332):99–110.Gordon JE, Abrahams MS, Dobbs M, et al (2002) Early reduction, arthrotomy, and cannulated screw fixation in unstable slipped capital femoral epiphysis treatment. J Pediatr Orthop; 22(3):352–358.Mooney JF III, Sanders JO, Browne RH, et al (2005) Management of unstable/acute slipped capital femoral epiphysis: results of a survey of the POSNA membership. J Pediatr Orthop; 25(2):162–166.Notzli HP, Siebenrock KA, Hempfing A, et al (2002) Perfusion of the femoral head during surgical dislocation of the hip. Monitoring by laser Doppler flowmetry. J Bone Joint Surg Br; 84(2):300–304.Peterson MD, Weiner DS, Green NE, et al (1997) Acute slipped capital femoral epiphysis: the value and safety of urgent manipulative reduction. J Pediatr Orthop; 17(5):648–654.Rattey T, Piehl F, Wright JG (1996) Acute slipped capital femoral epiphpysis. Review of outcomes and rates of avascular necrosis. J Bone Joint Surgery Am; 78(3):398–402.

Steven L Frick, MDPediatric Orthopaedics

Residency Program Director

Department of Orthopaedic Surgery

Carolinas Medical Center

Charlotte, NC, USA

steven.frick@carolinashealthcare.org

Virginia Casey, MDPediatric Orthopaedic Surgeon

OrthoCarolina

Charlotte, NC, USA

virginia.casey@orthocarolina.org

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