Soft Tissue Fillers and Facial Plastic Surgery Practice By Corey S. Maas MD™ October 23, 2011

The portfolio of products available for surgeons in the soft tissue filler market has grown rapidly over the past several years. Clinical indications have expanded beyond just simply the treating nasolabial folds and lip augmentation. Today, fillers are used for all types of facial contouring and fine line management. Market awareness has increased dramatically with the advent of Restylane and successful advertising and marketing campaigns. Additionally, there is a huge demand from the baby boomer generation, who want minimally invasive treatments to improve the changes associated with aging, including the development of rhytids and the loss of facial contour.

When studied carefully, it is an interesting dilemma for surgeons. The return on investment for performing injectable soft tissue augmentation and/or neuromodulators for patients in terms of time spent with patients is dramatically better than with surgical procedures, even in the cosmetic arena. These procedures in addition provide an entrée for patients for relationship building with the surgeon that may lead to future surgical procedures. The real dilemma that has occurred in recent years relates to whether or not busy cosmetic surgeons should use nurse or physician-assistant injectors as an adjunct to their surgical practice and as physician extenders. Using these providers represents a double-edge sword in current practice, as they diminish the ability of the surgeon to develop an intimate relationship with patients, which again may ultimately result in surgical cases. The key to success with the plethora of products available is being able to position them well within your practice. As providers, we need to be able to explain to our patients why we use certain products for certain areas, and this may include a number of different products for a single patient. We must understand each products benefits and limitations, and be able to successfully explain these to our patients.

Injectable Fillers – The Quest for Durability and Predictability

For purpose of classification, we have placed the available soft tissue fillers into a handful of basic categories. These include injectable biological materials, injectable synthesized bioactive materials, and injectable synthetic materials.

The techniques employed using these various materials include serial puncture, linear threading fanning, and of course, cross-hatching; with the latter two being primarily used for facial contouring (Figure 11-1). The long-held thought that all fillers should be injected intradermally has now been challenged by many clinicians who use the hyaluronic acid fillers subdermally. Some other products, such as Sculptra, which will be discussed later, are injected even deeper. Clearly, most collagen products, and in particular, CosmoDerm is an excellent product for intradermal use in the augmentation and correction of fine lines.

Biologics, Tissue-Derived

Among the biologic products that are tissue derived include:

1. Autologous fat

2. Zyplas

3. Resoplast, which is bovine collagen

4. Evolence procine collagen

5. Hylaform, Hylaform plus, which are hyaluronic acids derived from cock combs

6. Fascian or heterologous particles of fascia

7. Cymetra

8. Allerderm, which is heterologous sheets of dermis and SurgASSIST, which are porcine sheets of product

These products in general are effective and soft to palpation but have definite half-lives in vivo. Most of the biologic fillers as described are derived from animal tissues. These include bovine collagen from cowhide, Dermalogen and AlloDerm, as well as others from human tissue and Hylaform, which is derived from the comb of roosters. These are carefully synthesized and purified and placed in sterile syringes for immediate use off the shelf.

Among the more interesting of the recent developments is a porcine collagen called Evolence as trademarked by Colbar Inc. of Tel Aviv, Israel (Figure 11-2). This product has recently been acquired by Johnson & Johnson, which is developing an aesthetic care unit. Clinical trials are underway in the United States and the product promises one-year duration with deep dermal or subcutaneous placement.

AlloDerm and Surgasis are products that are derived from acellular dermis, Surgasis being from porcine dermis and AlloDerm being human derived. These require rehydration prior to implantation, and while their effectiveness was once touted as being permanent, most believe now that these products last from six to 12 months before reabsorption occurs. Autologous fat transfer is very popular and appropriate, in particular for facial contouring cases. In out experience, fat has limited value in lip, nasolabial fold, and tear trough deformity due to its unpredictable nature of reabsorption. With that said, autologous fat transfer remains one of the standards of care as it is quite easy to harvest fat from areas of fat excess, to centrifuge and/or wash the fat carefully, and to carefully prepare it for easy injection with a small-bore needle in cases of facial contouring. Most of the data associated with autologous fat suggest that it requires very careful handling and limited trauma to have long-term success. In general, extensive local nerve blocks are performed prior to fat transfer with gentle handling of the fat, and the best chance of success with fat transfer employs fine streaks or beads of fat applied in the deep subcutaneous tissue close to muscle (Figures 11-3a,b,c). One to four weeks of recovery are required for this due to the extensive swelling seen with that transfer and probably the best one can expect is 25 to 50% correction for intermediate and long-term results with fat transfer.

Each of these biological products has its advantages and disadvantages. In general, the main advantages include that they are injectable, they require limited anesthesia and are generally well accepted by patients, as they are soft and natural feeling. With the exception of fat transfer, these products have a very short recovery period. The disadvantages, particularly in the animal-derived products include the possibility of hypersensitivity reactions, which for example occur in one to four percent of patients injected with bovine or porcine collagen. These products generally have a temporary effect due to reabsorption which can be a disadvantage since they require repeat injections; however, this can also be looked at as somewhat of an advantage since it negates the long term risk of granuloma formation or infections which can be associated with permanent and synthetic injectable materials.

Synthesized Bioactive Products

The synthesized bioactive products that currently available include: CosmoDerm and CosmoPlast, which are recombinant human collagen products, Radiesse which is composed of calcium hydroxylapatite, Restylane, which is recombinant hyaluronic acid, Captique recombinant hyaluronic, Sculptra which is polylactic acid, and Juvéderm, which is homogeneous hyaluronic acid.

All these products are effective, soft and reliable, although sometimes they can result in modest amounts of inflammation that typically will last one or two days. Human collagen is provided in the form of CosmoDerm and CosmoPlast that is manufactured using recombinant technology and has similar handling characteristics to the previously known Zyplast and Zyderm products. This requires no skin testing and, in our practice CosmoDerm remains the product of choice for intradermal injection to treat fine lines.

These products are tissue-engineered from human dermal fibroblast cells. They are allowed to multiply on a collagen scaffold and the collagen then harvested, placed in syringes, and refrigerated until used. Another benefit to collagen is that it appears to enhance platelet aggregation, which may decrease bruising. Additionally, it contains lidocaine, which negates the need for local nerve blocks and reduces pain. In addition, there may be some benefit in local reduction in eosinophil degranulation, which theoretically results in decrease swelling, making it the injectable filler with the least amount of downtime. The biggest disadvantage to most of the collagen products is that they only last for two to three months.

The shorter duration hyaluronic acid products that are available include Hylaform and Captique. Hylaform, as previously mentioned, is derived from rooster combs, whereas Captique a 5.5 mg/dl concentration of human bioactive synthesized hyaluronic acid. Hyaluronic acid is a naturally occurring substance that is one of the most abundant glycosaminoglycans in the dermis. It is linear polysaceride made up of alternating units of glucuronic acid and glucosamine. It is identical in all species, which makes it unique in that it reduces the risk of inflammatory reactions after injections. Most of these products contain some degree of free hyaluronic acid in addition to modified and/or crosslink hyaluronic acid, which allows the product to be manufactured as a liquid, a gel, or a nearly solid filler.

Varying hydration levels of the hyaluronic acid fillers have an impact on their performance overall. Where Hylaform Plus and Captique have concentrations, as mentioned, of 5.5 mg/dl of HA, Restylane has 20 mg of HA, and Juvéderm has 24 mg of HA cross-linked per ml of water. These properties make them extremely hydrophilic, which results in more swelling upon injection of the product, as tissue fluids get absorbed by the higher concentration product.

Our clinical experience with Hylaform and Captique suggests that it lasts about as long as Zyplast, which is for most patients around three months, that it is certainly a safe product and there appears to be no long-range issues with Hylaform or Captique. The flow characteristics are quite good for both products, but it is difficult to find a place to position these products in practice given the performance of CosmoDerm and CosmoPlast and the alternative hyaluronic acids Juvéderm and Restylane.

Restylane has had a huge impact on the fillers market since its recent introduction. In its first year it more than doubled the soft tissue filler market, as it offered a substantial increase in durability and duration of effect. Restylane is a synthesized bioactive hyaluronic acid that is provided in a 20 mg/dl gel-particle suspension, 20 percent of which is uncrosslinked HA packaged in a 1 cc syringe (Figure 11-4).

In a randomized double-blind multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds, Restylane showed in both wrinkle severity rating scale and global aesthetic improvement scale assessments at six months that HA gel was superior to collagen products in the majority of patients. The technique of hyaluronic acid injection has been described as deep dermal. Our preference for this application is a subcutaneous injection with linear threading and fanning techniques being primary for the nasolabial fold and facial contouring, and linear threading for labial augmentation. The product is quite viscous and requires significant plunger-pressure and due to the discomfort associated with the product, we recommend local nerve blocks prior to injection. Juvéderm is another synthesized bioactive hyaluronic acid that is provided in 24 mg/dl solution in a presterilized syringe containing 0.8 ml of active product. Juvéderm is considerably easier to inject and softer than Restylane. We have found that it has some advantages in some applications and disadvantages in others. The majority of clinical data available in describing Juvéderm demonstrates similar performance characteristic to that of Restylane with the average duration of effect being in the six-month area. In particular, these data from the FDA trials were generated from the nasolabial fold region where long-term results were clearly demonstrated in these patients. The softness of Juvéderm allows less injection pressure and molding pressure when providing injections making it an excellent choice for augmentation of the tear trough and the nasolabial fold (Figures 11-5a,b; 11-6a,b). In contrast, in our practice, we find that the firmer nature of Restylane makes it ideal for labial augmentation.

In general, the biosynthesized hyaluronic acid products have some significant advantages in that they are easily injectable, they have very low hypersensitivity profiles, they are reversible, they are absorbable over time, they are soft and natural feeling, and they are relatively long lasting. Their disadvantages include that they may be considerably thicker and more difficult to inject than the collagen products, there is slightly more swelling and bruising, and they, in our opinion, require injectable anesthetic and/or local nerve blocks for patient comfort reasons.

Synthesized Bioactive Agents

Sculptra or New-Fill

Sculptra was recently introduced by the Dermix Company. It is an injectable poly-L-lactic acid product, which is provided as a powder for reconstitution. The product itself is very similar to Vicryl sutures and there is a minimal six-year experience in Europe with this product. The basic principal behind its use is that is stimulates an inflammatory response with the attendant deposition of soft tissues over time. The treatment is approved only use for HIV lipoatrophy, although the company is seeking cosmetic indications currently (Figure 11-7). Three to five treatments are required over a 12 to 18 month period with the patient seeing initial swelling and improvement followed by subsequent diminution of most of the initial augmentation which ultimately results in gradual restoration of volume due to the granulomatous inflammatory response.

Its use in cosmetic surgery has gained some traction in the United States while it has been diminishing generally in Europe with the advent and availability of other products that give immediate results. The Sculptra technique ideally requires the rehydration of the product or reconstitution at least six to 12 hours before the procedure to assure that there is no clogging of needles and deep placement in the subdermal tissue is appropriate in fanning or cross-hatching techniques. Subcutaneous nodules can occur as a result of uneven dispersion of the product, and in particularly, this product should be avoided in thin-skinned areas where a subcutaneous nodule might become quite evident. A study published in the Dermatologic Surgery literature, demonstrated satisfactory results in overall patient satisfaction on a long-term follow-up of 18 months, with 79 percent of patients requiring an average of three visits to receive the desired enhancement, and 21 percent requested additional treatment sessions beyond the initial three sessions to achieve the desired degree of augmentation. The preliminary studies for Sculptra all revolve around its use in lipodystrophy. Its role in other types of volume replacement is yet to be determined, but the most significant limiting factor preventing its widespread popularity is the absence of an immediate improvement.

Radiesse

Radiesse is a calcium hydroxylapatite product that is manufactured synthetically. It is a very thin paste, which comes ready to inject in a 1.3 cc syringe. FDA trials for nasolabial fold augmentation were completed and the data has been very promising suggesting a statistical preference over the control product and durability up to 12 months. Unpublished data from a European control trial against a long-acting hyaluronic acid filler demonstrated superiority, both for the patient and physician in palpability and longevity when applied in the nasolabial fold area. The company recommends using cross-hatching or fanning techniques to distribute the product using even beads into the subcutaneous tissues to provide augmentation and contouring for the face (Figures 11-8a,b,c). The product should not be used in the lips as nodule formations can occur. As mentioned before, FDA nasolabial fold trials. In general, Radiesse offers a great deal of promise for facial contouring and nasolabial fold augmentation. Although it is probably suboptimal in thin-skinned areas, such as the tear trough region, in the labial mandibular sulcus, the submalar region and the nasolabial fold, this may well prove to be the soft tissue filler of choice in many patients who want longer results with a soft and natural feel.

Synthetic Injectables

The list of synthetic injectables available worldwide has grown to greater than 40. In this country we are limited to basically two synthetic injectable products, which include injectable liquid silicone, which is not approved specifically for cosmetic use but for intraocular use in orbital reconstruction and Artefill medical, which has been recently approved for cosmetic soft tissue augmentation.

Artefill consists of methyl methacrylate microspheres of 30 to 40 microns in diameter. Recent advances in the product has resulted in an increase in absolute surface smoothness seen by electron microscopy, which presumably reduces the electrical charge that was previously produced during the manufacturing process, and thereby reduces the risk of the inflammatory and granulomas responses that were occasionally seen with the earlier Artecoll product used in Europe. It is supplied in sterile packages and is intended for subcutaneous injection. The company recommends serial injection be performed to ensure a gradual build up of the product and to avoid over augmentation secondary to over injection and/or a granulomatous and fibrous tissue response.

Silicone injection has been well described in the literature by Barnett and others. Many surgeons and authors have described its use in great success over many years of duration, and insist that it is completely safe in patients for soft tissue augmentation. It is given via a microdroplet technique.

One must keep in mind that potential complications with synthetic injectable agents, as they are permanent, include the permanent risk of inflammatory granulomatous nodularity and/or infection (Figures 11-9a-d). In addition, the aging face certainly changes over time and it will be interesting to trace patients over the long period to see if the correction generated by injection of these products is maintained as tissues become deflated and move under the effects of gravity in aging. In addition, these synthetic injectable agents must be precisely placed, as they can result in fullness in areas that are undesired which can result in permanent cosmetic morbidity.

Finally, synthetic injectables do offer some measurable risk of long-term complications including chronic granulomas, fibrosis, and/or chronic infection in which treatment would require wide local tissue excision. These risks must be discussed at length with the patients prior to the use of such products.

Treatment Strategies

With the plethora of products we have mentioned, one must develop a comprehensive strategy for patients when using these products. It is our suggestion that this be done on an anatomic and individual basis rather than selecting one product that might be good for all patients.

In general, for nasolabial fold augmentation we offer Radiesse, Restylane and Juvéderm. Similarly, at the area of the labiomandibular groove and submalar augmentation with facial aging and lipoatrophy that is attendant with facial aging, these same products offer the benefit of longer correction and fullness. Of these, Radiesse lasts the longest and because of its longevity, it has the potential to become the most popular product of the three in areas of thicker skin. We recommend Juvederm in areas of thin skin, such as the tear trough or nasojugal fold.

For the finer lines associated with the perilabial area, in the so-called smokers or radial lines, our preference remains Cosmoderm, as this can be placed carefully in the upper layers of the dermis without being identified through the skin surface with the blueish line apparent with most of the clear hyaluronic acid products. A wide area can be treated with serial-point injection and near complete smoothness or correction can be achieved.

For labial augmentation, our preference remains with Restylane, as it provides a degree of structural integrity to the lip border. It is slightly more difficult to inject than Juvéderm, but the structural benefits in terms of recreating the nature lip border are certainly beneficial. Alternatively, CosmoPlast can be used, which offers an immediate correction with short downtime, less chance of bruising, and no requirement for injection with a local anesthetic. Juvéderm certainly remain a good choice for this area as well.

In summary, our treatment strategies have evolved with the development of a number of new products that are available. Our general strategy includes an increasing use of fillers for subcutaneous volume enhancement and the primary products are we are using are Radiesse, Restylane, Juvéderm and Cosmoderm. New options may become available in the immediate future, in particular Evolence, the porcine collagen product, which promises to have a longer duration of effect than other forms of collagen and hylarunic acid products. As the choices increase we must continue to evolve our strategies for management of the aging patient, and keep open-minded about both the products and the newer applications for these products.

References

1. Bailin PL BM. Collagen implantation: Clinical applications and lesion selection. Journal of Dermatologic Surgery and Oncology. 1988;14((1)):49.

2. Castrow FF, 2nd, Krull EA. Injectable collagen implant–update. J Am Acad Dermatol. Dec 1983;9(6):889-893.

3. Maas CS, Papel ID, Greene D, Stoker DA. Complications of injectable synthetic polymers in facial augmentation. Dermatol Surg. Oct 1997;23(10):871-877.

4. Newcomer VD, Graham JH, Schaffert RR, Kaplan L. Sclerosing lipogranuloma resulting from exogenous lipids. AMA Arch Derm. Apr 1956;73(4):361-372.

5. Clark D, Hanke W, Swanson N. Dermal implants: safety of products injected for soft tissue augmentation. J. Am. Acad Dermatol 21: 992-998, 1989.

6. Skouge JW, Diwan RV. Soft tissue augmentation with injectable collagen In:

7. Papel ID, Nachlas NE eds. Facial Plastic and Reconstructive Surgery. St. Louis , Mosby Year Book, 1992: p. 208.

8. Ashinoff R. Overview: soft tissue augmentation. Clin Plast Surg. Oct 2000;27(4):479-487.

9. Skouge JW DR. Soft tissue augmentation with injectable collagen. In: Papel ID NN, ed. Facial Plastic and Reconstructive Surgery. 2 ed. St. Louis : Mosby; 1992:208.

10. Cheng JT, Perkins SW, Hamilton MM. Collagen and injectable fillers. Otolaryngol Clin North Am. Feb 2002;35(1):73-85, vi.

11. Narins RS, Bowman PH. Injectable skin fillers. Clin Plast Surg 32: 151-162, 2005

12. Krauss MC. Recent advances in soft tissue augmentation. Semin Cutan Med Surg. Jun 1999;18(2):119-128.

13. Duranti F, Salti G, Bovani B, Calandra M, Rosati ML. Injectable hyaluronic acid gel for soft tissue augmentation. A clinical and histological study. Dermatol Surg. Dec 1998;24(12):1317-1325.

14. Lowe NJ, Maxwell CA, Lowe P, Duick MG, Shah K. Hyaluronic acid skin fillers: adverse reactions and skin testing. J Am Acad Dermatol. Dec 2001;45(6):930-933.

15. Maas CS. Characteristics of implant materials. Arch Facial Plast Surg. 2000;2:67.

16. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A randomized, double-blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg. Jun 2003;29(6):588-595.

17. West TB, Alster TS. Autologous human collagen and dermal fibroblasts for soft tissue augmentation. Dermatol Surg. May 1998;24(5):510-512.

18. Boss WK Jr, Marko O. Isologen In: Klein AW ed. Tissue Augmentation in Clinical Practice: Procedures and Techniques. New York : Marcel Dekker, 1998 : 335-347.

19. Peer LA. Loss of weight and volume in human fat grafts. Plast Reconstr Surg 5: 217, 1950.

20. Spira M, Rosen T. Injectable soft tissue substitutes. Clin Plast Surg 20:181-8, 1993.

21. Ben-Hur N, Neuman Z. Siliconoma: another cutaneous response to dimethylpolysiloxane experimental study in mice. Plast Reconstr Surg. 1965; 36:629-631.

22. Achauer BM. A serious complication following medical-grade silicone injection of the face. Plast Reconstr Surg. 1983; 71:251-3.

23. Orentreich DS, Orentreich N. Injectable fluid silicone. In : Roengk RK Roenigk HH Jr. Eds. Dermatologic Surgery : Principles and Practice. New York : Marcel Dekker, 1989: 1349-1395.

24. Webster RC, Fuleihan NS , Gaunt JM, et al. Injectable silicone for small augmentations: twenty-year experience in humans. Am J Cosm Surg 1984; 1:1-7.

25. Rapaport MJ, Vinnik C, Zarem H. Injectable silicone: cause of facial nodules, cellulitis, ulceration, and migration. Aesthetic Plast Surg. May-Jun 1996;20(3):267-276.

26. Pollack S. Silicone, fibril, collagen implantation for facial lines and wrinkles. Journal of Dermatologic Surg and Oncology 16:957-961, 1990.

27. Burgess CM, Quiroga RM. Assessment of the safety and efficacy of poly-L-lactic acid for the treatmentof HIV-associated facial lipoatrophy. J Am Acad Dermatol. 2005 Feb;52(2):233-9.

28. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A randomized, double- blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg. 2003 Jun;29(6):588-95.

Figure Legends

Figure 11-1. Various injection techniques for soft tissue augmentation.

Figure 11-2. New collagen product Evolence promises up to 12 months of duration.

Figure 11-3a. Autologous fat transfer technique. Fat is harvested using a microcannula. It is then processed and washed to purify the fat. Various size microcannulas are used to inject using linear threading techniques for soft tissue augmentation.

Figure 11-3b. Fat harvest can be done during submental liposuction.

Figure 11-3c. Fat transfer to the lips.

Figure 11-4. Restylane.

Figures 11-5a,b. Restylane for lip augmentation.

Figures 11-6a,b. Restylane for nasojugal folds.

Figure 11-7. Sculptra in a patient with HIV lipodystrophy.

Figure 11-8a. Injection techniques for Radiesse injection.

Figure 11-8b. Radiesse in the nasolabial folds.

Figure 11-8c. Radiesse for lipodystrophy.

Figure 11-9a. Artecoll injection showing early erythema.

Figure 11-9b. Same patient shown in Figure 11-9a now with nodule formation (arrow).

Figures 11-9c,d. Silicone injection to lips with resultant nodularity and irregularity.