Dermal FillersThe Next GenerationTracey Hotta, BScN, RN, CPSN

In today's busy and demanding world, we no longer havethe luxury of taking weeks to recover from a surgical pro-

cedure and are more frequently seeking quicker alterna-tives. The use of dermal fillers meets this need but in noway replaces a surgical intervention. Previously, bovine col-lagen was the only approved dermal filler. However, todaythere are several options available including a human col-lagen, a variety of hyaluronic acids, and a permanentinjectable product. Each of the products has different uses,indications, and adverse reactions. The experienced injectornow has a wider selection of products from which tochoose to ensure that the patient receives what is bestsuited for his or her particular situation. These new prod-ucts are becoming increasingly popular, due to acceptabili-ty and affordability, but are not without potential complica-tions and adverse reactions. This article discusses the useof Cosmoderm/Cosmoplast, Hylaform, Restylane/Perlane,and Artecoll dermal fillers.

SKIN COMPOSITION

11 is important to understand the structure of theskin because the depth, composition, and indica-tions for use differ by product. The skin consists ofthree layers: the epidermis, the dermis, and the sub-cutaneous layer (see Figure 1).

Tracey Hotta, BScN, RN, CPSN, is President-Elect of the AmericanSociety of Plastic Surgical Nurses,

The author is an injeaion trainer for Inamed Aesthetics andCanderm Pharma, but she is not considered an employee of eithercompany. Her services are provided on a contract basis.

This article is modified from Hotta, T. (2004). Botox treatmentsand dermal fillers: The nonsurgica! alternatives. Brockton, fWlA:Western Schools, Available at http://www.westernschools.com.Used with permission.

The epidermis is the outetmost layer and it servesas our protective barrier. The epidermis consists of atightly packed layer of cells that are in a constantstate of cell renewal. This renewal process slows withaging as skin tends to feel heavier and fine linesappear The use of exfoliants (e.g., glycolic acid, vita-min A) are helpful to accelerate the renewal process,soften the hardened stratum comeum, and minimizethe appearance of fine lines.

The second layer, the dermis, is the most impor-tant layer when injecting dermal fillers. The dermisis comprised of two important substances: a loosenetwork o[ collagen fibers, within an interstitial sub-stance composed largely of hyaluronic acid.Collagen provides tensile strength to the dermis byforming a fiamework in which new cells can grow.The aging process causes the collagen framework toweaken and the skin to lose its elasticity. This resultsin the formation of lines and fun^ows on the facethat may be successfully treated with a dermal filler

Hyaluronic acid is a polysaccharide, which hasthe ability to attract water. Water is necessary tokeep the skin plump and moisturized. With advanc-ing age, the skin cells lose their ability to producehyaluronic acid. In addition, the molecular weightof the hyaluronic acid decreases, thus decreasingihe skin's ability to hold water and leading to finelines and folds. Both collagen and hyaluronic acidare commonly found in dermal fillers.

Third is the subcutaneous layer, which is a layerof fatty tissue that gives contour to the skin. Agingalso reduces the amount of subcutaneous tissue,which is not replaced with these dermal fillers.

PRODUCTS

Several types of dermal fillers exist and can be broad-ly grouped into collagen and hyalutonic acid fillers.

14 Plastic Surgical Nursing | January-March 2004 | Volume 24 | Number 1

JL-

Figure 1. The skin has 3 layers: The epidermis, the dermis,and the subcutaneous layer. (Used with permission fromCanderm Pharma, Saint-Laurent, Quebec, Canada.)

The ideal product would be biocompatible, nonanti-genic, nonpyrogenic, noninflammatoiT/, nonloxic,easy to use, nonmigratory, long lasting yet absorbable,natural looking, and affordable (see Table 1).

HUMAN COLLAGEN DERMAL FILLERS

Cosmoderm/Cosmoplast

Collagen is a naturally occurring protein that sup-ports various body tissue including skin and joints.Human-derived dermal fillers were approved inCanada in December 2002. The Food and DrugAdministration (FDA) approved them in the U.S. inMarch 2003. These are the only commercially avail-able dermal fillers in the world that contain naturalhuman collagen. The natural human collagen hasbeen purified from living dermal tissue grown understerile and controlled laboratory conditions. Becausethis product is human engineered, it is considered tobe less immunogenic and it is speculated that it willdegrade more slowly and last longer (Helwick, 2003).

Cosmodenn is composed of highly purified human-based collagen that is dispei sed in phosphate-bufferedphysiological saline containing 0.3% lidocaine.Lidocaine minimizes injection discomfort, which is agreat benefit especially when used in enhancing lipbordei's. Cosmoplasi contains the same properties, butis cross-linked with glutaraldehyde to increase itsstrength and possible longevity in the dermis. Becausethe collagen is of human origin, it does not require askin test prior to treatment. Therefore, the client mayhave a same-day treatment because the 28-day waitingperiod after a bovine collagen skin test is not needed.

Injection Tips

The collagen implant is injected either into theupper dermis (Cosmoderm) or the mid to deep der-

mis (Cosmoplast) to fill the deficit so the wrinkle orfold is more flush with the skin. The prefeired injec-tion technique for Cosmoderm and Cosmoplast isusing serial puncture with the accuratedepth-gauge (ADG) assist device. In the serial-punc-ture technique, multiple injections are made alongthe wrinkle in a smooth and continuous line. It isimportant to massage the treated area to ensureeven distribution ofthe product.

Cosmoderm is used in the treatment of superfi-cial lines and the glabella. It is placed in the pap-illary dermis with the needle's angle between 10°and 25°. An overcorrection of 200% is recom-mended e.xcept for perioral and periorbital lines.Overcon ection in these areas may be slow to resolvedue to minimal tissue stresses at these sites.

Cosmoplast is injected into the mid to deep retic-ular dermis and is ideal for treating deeper lines,enhancing lips, and smoothing facial scars that passthe "stretch" test. A stretch test is performed bystretching the defect or wrinkle between the indexfinger and the thumb. If the defect smoothes out, itis anticipated that there will be a satisfactory resultfrom the dermal filler. When injecting Cosmoplast,the needle should be placed at a 45° angle. Thetreated area should be corrected to 100%. Carefullayering of Cosmoderm and Cosmoplast can be per-formed to eliminate a wrinkle or scar but is bestdone 2 to 3 days after the initial treatment.

Cosmoderm over Cosmoplast must be kept refrig-erated. Removal from the refrigerator 30 minutesprior to injecting will help facilitate the injection pro-cedure. Inspection of the syringe prior to use istequired to ensure that the product has not becomeseparated. If separation occurs, the product shouldnot be used but returned back to the manufacturer.

Collagen treatments are not recommended for allpatients. The treatment is contraindicated in indi-viduals with an allergy to lidocaine, or a history ofanaphylactic reactions or allergic response to anycollagen product. It must be used cautiously inpatients with autoimmune diseases such asrheumatoid arthritis, scleroderma, and lupus ery-thematosus. These patients may have increased sus-ceptibility to hypersensitivity responses or acceler-ated clearance of their implants.

HYALURONIC ACID DERMAL FILLERS

The search for the perfect injectable material hasresulted in the development of hyaluronic-baseddern^al fillers, which have been flooding theinjectable market. The advantage of these productsis that they do not require a skin test. Hyaluronicacid is biocompatible because it is naturally occur-ring, in the same identical form, in the intercellularspace of the dermis. The two products that will be

Plastic Surgical Nursing | January-March 2004 | Volume 24 | Number 1 15

discussed will be Hylafomi and Restylane/Perlane.Restylane and Peilane were approved in Canada in1996, and Hylaform was approved in Canada in1998. In December 2003, Restylane received FDAapproval in the United States. At the time of thispublication, Hylaform is still undergoing clinicaltrials, awaiting FDA approval.

There are several limitations of natural hyaluron:it rapidly dissolves in water, it cannot hold its shape,and it is rapidly absorbed by the body. In the 1980snatural hyaluron was chemically modified, calledcross-linking, to produce a chemically stable productthat does not dissolve rapidly in water and becomesmore viscous. This new product is complementarv'for soft tissue enhancement because of its insolubili-ty and resistance to degradation and migration.

Besides the cross-linking it is important to assessthe particle size and the number of particles/ml ofeach product. The physical properties of the gel aremodified in each product to make it close to the idealfor its intended application. When assessing the crosssection of the skin, the epidermal layer has tightlypacked cells with very little intracellular space.Assessing further into the dermis, the cell structurebecomes less organized with a loose network of col-lagen and elastic fibers. Because of this characteris-tic, the particle size of the implant must be matchedto the tissues. Small implant particles, if injected intothe deep dermis, will be quickly lost because they caneasily pass through the coarse network of the tissuematrix. Conversely, if a large particle implant isinjected into the superficial dermis, the tissue matrixis much finer and it may stretch or tear the matrixcausing an uneven treatment result (see Figure 2).

ROOSTER COMB-DERIVED HYALURON

Hylaform

Hylaform, introduced to the Canadian market in 1998,is a highly purified source of hyaluronic acid that ischemically cross-linked and is extracted from roostercombs. The purification process used to eliminate theinflammatory fraction in rooster comb hyaluronicacid was developed by Dr. Balazs, the inventor ofHylaform over 25 years ago. Since that time theprocess has become well known and is widely used.

Each 0.75 mg syringe of Hylafot-m contains 5.5mg of Hylan B gel, sodium chloride, and water;however, the particle size is different for each rangeof product. The larger molecular network with larg-er gel particles provides better tissue filling.Hvlaform Fineline has very small particles, 300 pm,and is used to treat fine rhytids. periorbita! lines, orto overlay atop of Hylaform Plus. Hylafomi Regularis 500 |im and is ideal for treating perioral lines,facial rhytids, and shallow facial scars. HylaformPlus, the strongest of the three, has a pariicle size of

Figure 2. Hyaluron is a nonspecies-specific hydrophilichighly coiled polysaccharide that is present in all connec-tive tissue; in the skin it binds water and provides volumeand elasticity. (Used with permission from InamedAesthetics, Santa Barbara, California.)

700 pm, requiring less product to produce thedesired result. It is indicated for treatment of deepnasolabial folds, oral commissures, and lipenhancement. Because the source is extracted fromrooster combs, persons who are sensitive to avianproducts should be treated cautiously withHylafoim. Other precautions include a histoi-y ofherpes vims or active lesions in the treated area.

BACTERIAL FERMENTATION-DERIVEDHYALURON

Restylane and Perlane

Restylane was first introduced into Canada in 1996,2 years before Hylaform. It is a nonanimal-stabi-lized hyaluronic acid that is biosynthetically pro-duced by bacterial fermentation. This product alsouses cross-linking to stabilize it, so that thehyaluronic acid remains in the tissues for a longerperiod of time.

The resulting visco-elastic transparent gel has aconcentration of 20 mg/ml and is no longer water-soluble; however, it retains its affinity for water andits ability to swell and form hydrated copolymers.The product is available in three strengths, all ofwhich are 20 mg/ml of hyaluronic acid. The differ-ence between the products is the fact that they aretissue tailored.

Reslvlane Fine Lhie is injected into the superficialdermis to treat superficial facial lines. It has 200,000particles/ml with a particle size of 150 pm.

Restylane is injected into the mid dermis and isindicated for the treatment of perioral lines, shallowfacial folds, and scars. It contains 100,000 parti-cles/ml with a particle size of 250 pm.

Perlane is injected into the deep dermis and isideal for the treatment of naso-labial folds, oral com-

16 Plastic Surgical Nursing I January-March 2004 I Volume 24 I Number 1

missures, and lip enhancement. It contains 10,000particles/ml, micron size is 1,000 pm. Because thisproduct has a higher concentration of hyaluronicacid, there tends to be more swelling than with theother injectables. Because this area is disturbed bythe injection procedure, the manufacturer warns thatpatients should not expose the treated area to intenseheat or cold for the first few days after the injectionto avoid the risk of inflammation. Upon becomingintegrated into the body the products will adjust to anormal body temperature.

Injection Tips

The hyaluronic acid products are best injected byusing a linear threading technique. In the linearthreading technique, the needle's full length isinserted under the wrinkle and the product is inject-ed while slowly pulling the needle backwards. Caremust be taken to stop injecting before the needle iscompletely removed. When treating fine wrinklesand superficial scars, the Hylaform Fineline/Restylane Fine Line is best placed in the papillarydermis using a 30-gauge hypodermic needle.Enough material should be injected so the defect isfully corrected but with no degree of overcorrection.

For deeper furrow lines or scars, deep placementof Hylaform Plus or Perlane in the mid to deep der-mis (reticular layer) is typically needed to obtainconection and is best done by using a 27-gauge nee-dle. This may be layered on top using the Finelinematerial. The site should be treated only to elimi-nate the wrinkle or scar with no overcorrection. It isimportant to note that hyaluronic acid stings uponinjection; therefore, patients should be given theoption of a topical anesthetic or a dental block(numbing of the pedoral area by injecting a localanesthetic into the nerve supply to the lips).

PERMANENT INJECTABLE DERMAL FILLER

Artecoll

Artecoll is a sterile microiniplant that consists of high-ly purified polymethyl methacrylate (PMMA) parti-cles suspended in a bovine collagen solution alongwith lidocaine. These microspheres have a definedsize of 30-40 pm with a smooth, residue-free surface.The microspheres are large enough to escape phago-cytosis but small enough that they may be injectedsubdermally through a 27-gauge hypodermic needle.During the first lew weeks the surrounding collagen isphagocytized and the PMMA particles foim clusters.

Artecoll differs from the temporary injectables inthat the procedure does not yield an immediateresult. The objective of Aitecoll is to initiate libro-plasia and collagen synthesis. There will be tempo-

rai-y correction for 2 to 4 weeks and then as the col-lagen is reabsorbed, their lines will reappear or lipswill return to the size they were prior to injection.After 3 weeks the histological climax of fibroblastactivity is reached. At about the 6- to 8-week periodthere will start to be a gradual filling in of the line.At 3 months the implant is predominantly interwov-en with fibroblasts and collagen fibers and theprocess of fibroplasia is usually complete. Completecorrection may require two or three injection ses-sions, with the final result taking up to 1 to 2 years.

Artecoll contains 0.3% lidocaine so there is a smallamount of anesthetic effect as the product is beinginjected. The PMMA particles must be delivered inbovine collagen; thus, the manufacturer recommendsa collagen skin test. The risk of being allergic to thecollagen in Artecoll is <1% (Canderm PharmaIncorporated, 2001). There is a lower concentration ofcollagen in Artecoll when compared to other bovinecollagen products. Artecoll is contraindicated In thosewho have a positive skin test, allergy to lidocaine,known immune diseases, a histor-y of keioid fornia-tion, or flaccid skin. Cun^ent treatment with steroidsmay inhibit growth of connective tissue.

Because the product is injected in the deep dermisand the needle is kept in constant motion so it is dis-tributed in a scaffolding pattei^n, there is an increasedrisk of bruising. If too much product is placed in onearea, the implanted material may be palpable andmay lead to nodule formation. An implant noduleconsists of microparticles and its normal tissue reac-tion. The nodule may become deformed, displaced,and palpable in the soft tissue of the lips and is some-times visible. A rare but potential side eHect is the for-mation of a granuloma. It becomes obvious 6 to 12months after the injection of any kind of dermal fillersubstance. A granuloma is a growing lump and itoccurs at all implant sites simultaneously Withouttreatment granulomas can grow to the size of a beanbut resolve spontaneously after several years. Bothnodules and granulomas react well to intralesionallyinjected Kenahg, a steroid that helps to soften scar tis-sue. The Kenalog must be injected carefully into lhenodule because if it is injected into the surroundingtissue it may cause skin atrophy. Surgical excisionmay be needed for nodules/granulomas ihat do notrespond to the steroid injection.

Injection Tips

when Artecoll is injected, the product is placed sub-dermally. This may be measured by piercing throughthe skin at a 90° angle and placing the needle at adepth of 2 bevel lengths or a 2 mm depth.Immediately turn the needle so it is parallel with theskins surface. The product is packaged with a 26-gauge h\podennic needle, but a 27-gauge may beused in the more sensitive areas. The product should

Plastic Surgical Nursing | January-March 2004 | Volume 24 | Number I 17

TABLE 1 Available Product Comparisons

(Q-MeUppsal

Artecoll(Rofil MedicalInternational,

Composition

Source

Placement

Year of HealthProtectionBranch approval

Date of FDAapproval

Considerations

5.5 mg hyaluron8.5 mg sodium

chlorideWater

Particle Size

20 mg hyaluronWater

Fineline 200 ig

Regular 300 fig

Plus 700 M.g

Fine line 150 -g

Restyiane 250 |xg

Perlane 1000 fig

A glycosaminogiycan biopolymercomposed of monosaccharides,giving it the ability to bind waterand form hydrated polymers ofhigh viscosity.

Rooster combs Bacteria

Mid-dermisLinear threading techniqueDo not overinject; overcorrection may

cause pressure on adjacent tissueand migration of product.

1998 1996

35 mg/ml saline.3% lidocaine

35 mg/ml saline.3 % lidocaine

cross-linked withglutaraldehyde

PMMA beads dispersedin 3.5% collagensolution and0.3% lidocaine

The suspended collagen forms a softcohesive network of fibers, which is

responsible for restoring contour.

Genetically engineered live human tissue

Papillary dermis Mid- to deepreticular dermis

Serial puncture technique with assist deviceOvercorrect by Do not overcorrect

150-200%

2002 2002

Still awaiting FDA December 2003 2003approval

No skin test requiredLast 4-6 monthsStore at room temperatureDiscomfort on injectionIs sensitive to moldingImmediate results but may have 1-2

days of erythema and swellingMay produce a gray streak if too

superficial

2003

Contains lidocaine to ease injectionRequires refrigerationImmediate results with minimal

swellingLasts 4-6 monthsMay stimulate own collagen formation

over time; therefore, less product isneeded for ongoing treatments

Artecoll uses the body'snatural ability toencapsulate foreignbodies by the formation of connectivetissue surrounding thePMMA microspheres.

Bovine collagen from aclosed herd in theUnited States.

Sub-dermal placementusing 27- or 26-Chypodermic needle

0.5 ml injected into onesite per treatment;may re-inject in3 months

1998

Still awaiting FDAapproval

Requires a skin test<0.1% risk of allergic

reactionRequires refrigeration but

should be removed 4hours before injecting

Results are complete in3 months when theimplant becomesinterwoven byfibroblasts andcollagen fibers

May require a series oftreatments

Requires precise deepdermal injectiontechnique to preventrisk of palpable lump

Long-lasting results

Nate. PMMA - polymethyi-methacrylate; FDA - Food and Drug Administration. Data from information obtained in the physician package inserts fromInamed Corporation, Q-Med AB, and Rofil Medical.

18 Plastic Surgical Nursing | January-March 2004 | Volume 24 | Number 1

be injected using the tunneling technique with theneedle in constant motion. This injection techniqueallows the Aitecoll to be placed in a scaffold patternwith not too much product in one area. Remember tostop injecting when the needle is being removed.Gently massage the implant between your thumb andfinger to ensure even distribution of the product.

It is not uncommon for the tip of the needle tobecome clogged with Artecoll or a bit of dermis. Ifthis occurs, change the needle and start again.Forcing the plunger will result in injecting an unde-sired amount of Artecoll in one place.

The Artecoll must be stored in the refrigeratorand should be removed 4 hours prior to an injectiontreatment. A syringe may be stored at room temper-ature, away from sunlight and heat, to maintainreadiness for the potential "emergency" Artecolltreatment. Examine the syringe for separation ofproduct prior to injecting. Heat and light can lead toproduct separation; if this occurs the materialshould be discarded.

NURSING CONSIDERATIONS

The concept of a dermal filler injection being alunch-hour treatment is a great marketing tool, butthe client must be warned of the postinjection reac-tions that may occur with all of the injections. Eventhough cosmetics may be applied 30 minutes afterthe injection, residual evidence of the treatmentmay yet remain.

• Anticipated side effects after any injection mayinclude one or more of the following;

• Ei-ythema, which may last 1 to 2 hours and maybe camouflaged with cosmetics.

• Swelling, which may last 2 to 12 hours dependingon the product used. There tends to be increasedswelling with hyaluronic products because oftheir water-binding properties.

• Localized tenderness.• Palpable lumpiness, which usually resolves with-

in 1 to 2 weeks.• The risk of bruising. To minimize this risk, clients

who take antiinflammatories, vitamin E, oraspirin are advised to discontinue use approxi-mately 2 to 3 days prior to the injection.

• Recurrence of a cold sore. Lip-enhancementclients with a histoiT of the herpes virus are at anincreased risk of developing a posttreatment coldsore. This is due to the fact that the herpes viruslives within the vermillion border of the lip,which is also the area injected. Clients with achronic history of cold sores or who have had anoutbreak in the past 6 months should be pre-scribed an antiviral medication (e.g., Acyclovir)as a prophylactic measure.

CONCLUSION

The management of wrinkles, furrows, and aging skinis a relentless quest to match facial appearance withperceived age, and can be achieved to a certain extentwith dermal fillers such as collagen and hyaluronicacid products. While nonsurgical demial filler prod-ucts are no substitute for the more dramatic and per-manent results of surgery, they have become safer, lessexpensive, and ai e more user fiiendly. Still, the searchfor the perfect injectable dermal filler continues.

REFERENCES

Canderm Pharma Incorporated. (2001). Arlecoll productdescription—aseptic product. Retrieved September 20,2003, from v^'ww.canderm.com

Helwick. C. (2003). An injeclion of talent: Improved human-engineered collagen, hyaluronic acid lop list of new anti-aging offerings. Cosmetic Surgery Times, May 1, 2003.

BIBLIOGRAPHYAmerican Society of Plastic Surgeons. (2002). American

Society of Plastic Surgeons Statistics. Retrieved September20. 2003 fiom wuw.plasticsurgery.org/public_education/2002statistics.crm

Duranti, F, Saiti, G., Bovani. B., Calandra, M., & Rosati, M.L. (1998). Injectable hyaluronic acid gel for sofl tissueaugmentation: A clinical and histological study.Demiatological Surgery, 24(12), 1317-1325.

Inamed Coiporation. (2002). Ccsniodenn Cosmoplast humanbased collagen implant—physician package insert. SantaBarbara, CA: Inamed Coiporation.

Inamed Coiporation. (2003). Cosmodenn and Cosmoplasthuman based collagen explained—physician package insert.Santa Barbara, CA: Inamed Corporation.

Inamed Corporation. (2003). Cosmodenn and Cosmoplast—collagen replacement therapy without the skin test. RetrievedSeptember 24, 2003 from www.inamed.com

Lemperle, G., Romano, J. J., & Busso, M. (2002). Soft tissueaugmentation with Artecoll: 10-year history, indications,technique, and potential side effects. Dermatology Sttrgery2916), 573-587.

Mang, W. L., & Sawatzki, K. (1998). Complications afterimplantation of PMMA (or soft tissue augmentation.Zeitschrift fur Haut-krankheiten, 73( 1), 42-44.

Manna, F, Dentinr, M., Desideri. O., DePita, O., Mortilia, E., &.Maras, B. (1999). Comparative chemical evaluation of twocommercially available derivatives of hyalur-onic acid(HylafoiTn from rooster combs and Restylane fr-om strepto-coccus) used for soft tissue augmentation. Joumal of Euro-pean Academy of Dermatology and Veuereology, 13, 183-192.

McGhan Medical Corporation. (2000). Zydenn collagen a}idZyplast collagen explained. Santa Barbara, CA: McGhanMedical Corporation.

Olenius, M. (1998). The first clinical study using a newbiodegradable implant for the treatment of lips, wrinkles,and folds. Aesthetic Plastic Surgery 22, 97-101.

Q-Med AB. (2003). Restylane—natural heautv, from Sweden.Retrieved September 22, 2003, from wwvv.restylane.com/professional/DynPage.aspx?id^5318 mnl=230.

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