The ideal injectable material for filling wrinkles and restoring volume to the face should not only offer aesthetic, reproducible, and long-lasting results but should also be safe, with minimal complications and risk of migration. It should also be easy to use and reasonably priced.

In recent years, a variety of injectable fillers has appeared on the international market, including both synthetic products and those derived from natural substances or extracted from animal or human cells. I have drawn up a list of the available resorbable filler products, particularly those most frequently used, and have studied their chemical natures, formulations, methods of injection or implantation, most common indications, and possible side effects.

The different families of resorbable filling materials are:

• Collagen-containing fillers, comprising substances containing collagen obtained from human or animal cells;

• Autologous fat;

• Fillers containing hyaluronic acid, either of animal origin or biosynthetic; and

• Products containing polylactic acid.

Products of mixed composition that contain both resorbable and nonresorbable components were excluded from this study.

Human collagen

A number of firms market human collagen, either in the form of autologous collagen obtained from the donor or isogenic collagen obtained from a donor or even cadavers. These products have a very limited distribution in Europe but are used more widely in the United States.

Autogenic human collagen

The use of autogenic human collagen eliminates any risk of virus or prion transmission. However, the preparation time for the product is relatively long and requires a prior surgical procedure for sampling of the material, which is reinjected after treatment by a competent laboratory.

Autologen

Introduced at the end of the 1980s, Autologen (Collagenesis, Inc., Beverly, MA) was the first autologous injectable agent on the market. Autologen is a dispersion of intact collagen fibers and a matrix of collagen tissue obtained from the clean skin of the patient during a plastic surgery procedure (mammaplasty, abdominoplasty, face lift, blepharoplasty). A skin biopsy is inadequate. Because the injected material is autologous and no allergic reactions were reported in a sufficient number of patients, the United States Food and Drug Administration (FDA) does not consider it necessary to perform a test before Augologen injection.

The skin excision, placed in a sterile container, is sent to the manufacturer’s laboratory for treatment. As a general rule, 10 to 13 cm² of excised skin is requred to produce 1 mL of Autologen 5%.

The dermis is sprayed into a sterile buffer to form a dispersion of intact collagen fibers. The dispersed collagen fibers are washed in a sterile phosphate buffer and concentrated by means of centrifugation. The substance obtained is packaged in sterile 1-mL Luer-Lok syringes and labeled with a unique identification code for the donor-recipient. Preparation of Autologen by the laboratory takes 3 to 4 weeks; the practitioner may then store the finished product in a refrigerator for as long as 6 months.

Autologen is injected into the middle dermis with a 30-gauge needle. Because the injection is painful and the preparation does not contain an anesthetic, anesthesia (EMLA, AstaZeneca Pharmaceuticals, Wilmington, DE; or lidocaine injection) of the treatment area is recommended. It is also recommended that the syringe be taken out of the refrigerator approximately 1 hour before the injection. At least 3 injections, a few weeks apart, are needed to obtain a satisfactory result, provided that each treatment is overcorrected by 30%.

A comparative trial between Zyplast (Inamed, Santa Barbara, CA) and Autologen has shown no significant difference between these fillers with respect to clinical persistence 12 weeks after injection. Unfortunately, the trial was not continued beyond 12 weeks.

A trial in 25 patients demonstrated that 1 injection produced correction of 50% to 75% for as long as 3 months or 50% at 6 months, that 2 injections produced correction of 75% after 6 months, and that 3 injections produced correction of more than 75% at 12 months.Fagien described results 6 months after treatment of deep glabellar wrinkles with Autologen (4 sessions, 1.5 mL of Autologen in total). This author also noted good results 6 months after injection of 4.0 mL of Autologen (3 sessions) in the treatment of deep nasolabial folds.

The duration of treatment depends on the region treated, the injection technique, and the volume of Autologen administered. No significant side effects have been reported. It must be noted, however, that moderately severe erythema may last for 48 hours after the injection.Preparation of the autologous collagen from a patient-tissue sample is expensive ($995/sample), and yield varies, depending on the individual and the anatomic areas from which collagen is harvested.

Isolagen

Since 1998, autologous fibroblast cultures have been used to correct wrinkles, scars, and other skin defects. Boss et aldescribed a method of injecting autologous fibroblasts obtained from a 3-mm skin excision from the retroauricular area, an area protected from UV light. The sample is immediately placed in a culture medium provided by Isolagen Laboratories (Houston, TX) and must reach the laboratory by the day after sampling in an isothermic container. The fibroblasts and type I collagen are developed in a culture medium for 4 to 6 weeks. Six weeks after sampling, an injection test (0.1 mL) is administered to the patient in the forearm; any sign of an allergic reaction is recorded. Two weeks after the test, approximately 1 mL of the autologous material is available for implantation. Additional injections, 1 mL each, are available every 2 weeks until optimal correction is obtained.

Isolagen is a very fluid liquid that is injected into the superficial dermis with a 30-gauge needle. Overcorrection of 300% is recommended for suitable aesthetic results. When the material is implanted, the carrier is absorbed and the overcorrection rapidly disappears. As a rule, 4 to 6 injection sessions are required.

The level of correction achieved depends on the defect, the patient’s age, and the ability of the patient’s fibro-blasts to create collagen. Patients older than 60 years are not good candidates for this technique because their skin is no longer able to produce vigorous fibroblasts. Boss et alreported a study in which 92% of 94 patients were satisfied with the results 12 months after treatment. In another study, histologic sections taken 6 months after treatment (3 1-mL injections administered at 2- to 3-week intervals) demonstrated an improvement in the thickness and density of collagen.