Treatment of ACL and cartilage injurythe Japanese contribution

Mitsuo Ochi,M.D.,Ph.D.

President of Hiroshima university

IOC Advanced Team Physician Course 2019

2

Watanabe No.21 Arthroscope (1959)

In 1964, Dr. Jackson visited Japan to study arthroscopy under Dr. Watanabe and

returned to Canada with this arthroscope and performed arthroscopic examinations,

resulting in that the Watanabe No.21 model became very popular in North America.

Father of the Arthroscopy

3

The first case of meniscectomy under arthroscopy in 1962

• 1) Treatment of ACL injury

• 2) Treatment of Cartilage injury

ACL injury about 200,0000 in USA

ACL injury mechanism More than 200,000 / year

Krosshaug T et al.:

Am J Sports Med. 2007

ACL injury mechanism

Anatomic single-bundleACL reconstruction

ACL reconstruction

Anatomic double-bundleACL reconstruction

T. Muneta 1999

K. Yasuda 2004

BTB or hamstring tendons

Hamstring tendons

ACL-R in Japan : about 20,000 per year

• 2 tibial and femoral tunnels

• 4-strand semitendinosus tendon

• Pull-out fixation with EndoButtons

• Started at July, 1994

Two-bundle reconstruction of the anterior cruciate ligament

using semitendinous tendon with endobuttonsArthroscopy 1999

Takeshi Muneta et al

This is the first report on double bundle ACL-R

under arthroscopy.

What is your surgical procedure for this case?

20 yrs old female basket ball player

Pivot shift :1+ , KT 2000 side to side difference: 5mm

The ACL graft was passed via over the top route and

fixed to the femur through the lateral femoral incision.

ACL remnant

(Adachi N, Ochi M, et al., Arch Orthop Trauma Surg, 2000)

Two incisions of Tibia and Femur

Arthroscopic ACL Augmentation ( since 1992)

1) Biomechanical function of preserved remnant

Crain EH, et al., Arthroscopy 2005

Nakamae A, Ochi M, et al., Arthroscopy 2010

Nakase J, et al. Knee Surg Sports Traumatol Arthrosc 2013

2) Biosensor function of preserved remnant

Adachi N, Ochi M, et al., Acta Orthop Scand 2002

Ochi M et al., JBJS Br 1999 and 2002

3) Enhancement of healing process of grafted tendon

Mifune Y, et al., AJSM 2013

Matsumoto T, et al., AJSM 2012

Sun Y, et al., Knee 2013

Novaretti JV, et al. Am J Sports Med. 2018

Several potential advantages of augmentation

Arthroscopic ACL AM or PL bundle reconstruction preserving

ACL remnant with one incision technique

using EndoButton-doubled semitendinosus tendon complex

ACL remnant

Since 1996

Doubled semitendinosus tendon

Ochi M et al., Arthroscopy in 2006

ACL-R using Semi-T

Endobutton

12 mm4 mm

Graf and Rosenberg

Mechanical weakpoint

Reconstructed ACL

ACL –R rupture of threads (the weakpoint)

16 years old female

Concepts of New Constructs

Hamstring

tendons

Artificial ligament

OCHI et al. knee in 1996

AB

Loop Ligament C

OCHI et al. knee in 1996

Shimane-Leeds Loop Ligament with Endobutton

Endobutton Continuous Loop

（Endobutton CL)

(Smith & Nephew)

Endobutton CL was commercially available in 2000.

Video: ACL augmentation

Dr. Shino’s contribution in ACL-R

Canine Experiment on Allograft ACLR

Shino, J Bone Joint Surg, 1984

Fresh-frozen Patellar Tendon w/o Bone Plugs

Graft in situ

Human Trial on ACL Allograft

Shino, JBJS, 1986

The first report in the world

Anatomical Triple Bundle ( ATB ) ACLR

Endo-button CLs

DSP + Screw

Shino, Oper Tech Orthop, 2005Tanaka, Shino, KSSTA, 2011Mae, Shino, Arthroscopy, 2013Shino,JOS,2015Take, Shino, Arthrosocpy, 2018

Pullout sutures

Prepared Semi-T Tendon Graft

Attachments of 3 ACL Bundles

Otsubo, Suzuki, Shino, KSSTA

IMPL

AM IM

AM

PL

Resident’s ridge

Three bundles of ACL

AMIMPL

Anatomical Rectangular Tunnel (ART) ACLR w/ BTB Graft

Shino, Arthroscopy, 2005, 2008Suzuki, Shino, Arthroscopy, 2014Shino, JOS, 2015

DSP + Screw

Interference Screw

Parallelepiped bone plug (10 x 5 x 15 mm)

BTB Graft

BTB (Bone-Patellar Tendon-Bone ) Graft:

⚫Rectangle in cross section

⚫Strength (120% of N. ACL in max. failure load )

⚫Bone plugs

Cf. Cross section@ ACL mid-substance

10-mm wide BTB Graft

Fiber Arrangement of ACL

Friedrich, O’Brien, 1990

Dr. Kurosaka

Prototype of Kurosaka Screw （＄２０）

Made at a small factory

The tensile test of normal ACL and BTB fixed with a screw

ACL

Patellar tendon screwed9.0mm

Patellar tendon screwedAO6.5mm

Patellar tendon fixed with large diameter screw showed steeper (Higher stiffness) load

elongation curve at the beginning of the tensile test

AJSM 1987This screw is a standard fixation material.

Electromagnetic sensor devise

Real time analysis of knee kinematics

Hoshino Y, et al. Am J Sports Med 2007

Dr. Yasuda

Clinical Studies to Establish Anatomic DB ACL Reconstruction (in the 2000s)

(Arthroscopy 2004: Cited 355 times, Top 1%) (Arthroscopy 2006; Cited 326 times, Top 1% )

AMPL

Clinical Challenges to Preserve an ACL Remnant Tissue in ACLR (in the 2010s)

(Arthroscopy 2012: Cited 37 times)

(AJSM 2016; Cited 27 times)

AMB

PLB

Treatment of Cartilage injury

Structure of articular cartilage

• Hyaline cartilage

• no vessels

• A small number of cells

tangential

zone

tidemark

subchondral

bone

calcified zone

transitional

zone

radial zone

Limited spontaneous healing capacity

Autologous osteochondral mosaicplasty

Autologous Chondrocyte Implantation

(Brittberg M, Peterson L, et al, New Eng J Med, 1994)

Dr. Lars Peterson

Dr. M.Britteberg

Periosteum

Cartilage

Subchondral bone

Leakage of grafted chondrocytes from the grafted portion

Uneven distribution of

grafted cells

Problems of their procedure

Second generation of ACI (matrix assisted ACI) from 1996

Telopeptide

(antigenicity)This collagen has been used for human since 1986 in Japan.

Atelocollagen

AtelocollagenHam F-12 medium

Patient’s serum＋antibiotics5% CO2 / 95% air

3 weeks

Isolated chondrocytes

(scaffold)

4) Implantation 5) Suture of the remaining periosteum

3) Pull out suture of the periosteum

Defect 1) Curettage2) Extraction of

the periosteum

Implantation of tissue-engineered cartilage since 1996

2nd generation of Autologous chondrocyte implantation(28 y.o female)

1 year

The first case in the world

15 year-old male: OCD of left med. femoral condyle

15 years after implantation

Multicenter clinical trial

after approval of Japanese Ministry of Health,

Labour & welfare

(JST)

Hiroshima U.

Hospital

Osaka U. Engineering

Department

Shimane Univ.

Hospital

Hokkaido Univ.

Hospital

Tokyo Med. Dent.

Univ.Hospital

J-TECVenture company

for regenerative medicine

Nagoya

Mitsubishi

Hospital

Total evaluation

Extremely useful &

useful

28 cases (93.3%)

Extremely useful &

useful

31 cases (96.9%)

有効性評価（N=30）

極めて有効25例(83.3%)

有効3例(10%)

どちらとも言えない2例(6.7%)

無効

0例(0%)

安全性評価（N=32)

極めて安全29例(90.6%)

安全2例(6.25%)

安全性に疑問1例(3.1%)

安全でない0例(0%)

有用性評価（N=30）

極めて有用23例(76.7%)

有用5例(16.7%)

どちらとも言えない

1例(3.3%)

好ましくない1例(3.3%)

Extremely useful & useful

28 cases（93.3％）

JACC (brand name)

UsefulnessSafetyEffectiveness

Tohyama H, Ochi M. et al. (JOS 2009)

JACC from J-TEC

1st April 2013 approved as an item

covered by Japanese Health Insurance

JACC Certified Hospitals and Doctors

2013 2014 2015 2016

0

200

400

600

800

1000

1200

1400

Certified Doctor

Certified Hospital

183

918

226

1,158

❖Conditions of marketing authorization and reimbursement of JACC require the certification of hospitals and doctors.

JACC has been used for 800 knees until Mar 2019.

Clinical results of our procedure

1) Ochi M, et al ( Artif Organs, 2001)

2) Ochi M, et al ( JBJS-Br, 2002)

3) Sato M, Ochi M, et al ( J Shoulder Elbow Surg 2004)

4) Ochi M, et al ( Artif Organs, 2004)

5）Adachi N, Ochi M. et al ( KSSTA 2004)6) Agung M, Ochi M, et al ( Arthroscopy 2004)

7) Adachi N, Ochi M. et al ( Arthroscopy 2005)

8) Adachi N, Ochi M. et al (J Rheumatology 2005)

9) Adachi N, Ochi M. et al (Arthroscopy 2006)

10) Adachi N, Ochi M. et al.( JBJS Am 2007)

11) Tohyama H, Ochi M. et al. (JOS 2009)

12) Takazawa T, Ochi M. et al. (JOS 2012)

13) Adachi N., Ochi M. et al (KSSTA in 2014)

Remaining problems：Limitation of cell proliferation

2 staged surgery and large incision

Difficulty in large defects and aged patients

Invasive surgery

（Aljazeera English The cure)Cartilage repair using magnet

Bone Marrow Derived-MSCsin Cartilage Repair

Clinical study using Bone Marrow Dreived Mesenchymal Stem Cells (BMMSC)

HTO+BMMSCs(+) vs HTO+BMMSCs(-)

• Clinical evaluations: No significant @ 16M

• Arthroscopic & Histological grading:

MSCs therapy was better @ 10M !!

Wakitani S, et al. Osteoarthritis Cartilage 2002

MSC(+) @40weeks MSC(-) @43weeks

Synovial MSCs

Sakaguchi Y, Sekiya I, et al. Arthritis Rheum 2005.

Toluidine blue staining

Synovium-derived cells have the superior capacity

for chondrogenesis.

Arthroscopic transplantation of synovial MSCs for cartilage defect

Synovium collection Digestion Expansion with

autologous serum

for 14 days

Cell transplantation

Before 1 year

Tokyo Medical and Dental University

Ichiro Sekiya and Takeshi Muneta

Cartilage regeneration by Tissue Engineered Construct (TEC) derived from Synovial MSC

Large animal study to clinical trial

Stable cell

expansion

Isolation of MSCs

from synovium

: Cell

: ECM

Monolayer

TEC

Scaffold–free Tissue engineered

construct (TEC)

Development of TEC

ECM production

promoted by Ascorbic acid

Multi-layered cell matrix

construct via Cytoskeletal

contraction

Gene Transfer

Drug

Low oxygen

Mechanical stress

Chondrogenesis of TEC

Chondrogenic TEC

6 month

TEC

Biomaterials 2007 2010 2013

Tissue Engineering, 2008 200

Cell Transplant 2008 eCM 2012

N.Nakamura

Cell Sheet (Dr. Sato)

• I have talked about treatments of ACL injury and cartilage injury.

The oldest concept of endoscopy in Japan printed in 1794

Thank you