No abstract

We examined collagen materials for soft tissue augmentation [Zyderm Collagen Implant (ZCI), glutaraldehyde cross-linked (GAX) collagen, and Koken Atelocollagen (Atelocollagen)]; hemostatic collagens [Gelfoam Gelatin Powder (Gelfoam), Avitene Microfibrillar Collagen Hemostat (Avitene), and Collastat Collagen Hemostat (Collastat)]; and reconstituted, intact fibrillar collagen from bovine skin in a subcutaneous guinea pig model. After 11, 25, and 39 days in situ, explants from animals injected with GAX collagen demonstrated greater wet-weight persistence than all other materials. Conversely, at all time points, the explants of Atelocollagen were the least persistent. Following 25 days in vivo, explants were examined using differential scanning calorimetry; ZCI and Atelocollagen displayed thermal transition temperatures of 58 degrees C. Avitene and Gelfoam explants displayed transition points of 30 degrees C and 32 degrees C, indicating denatured or cleaved collagen. By contrast, GAX collagen explants had a high (68 degrees C) transition temperature, reflecting its cross-linking. With respect to immunogenicity, day 39 sera from ZCI treated animals showed significantly lower titers in the ELISA to their respective implant collagen than all other groups examined, while antibody activity in the GAX collagen, Gelfoam, Atelocollagen, and intact collagen groups were not significantly different. Collastat elicited antibodies with a greater affinity than observed in these previous groups. Sera from Avitene treated animals demonstrated the highest antibody levels and were the only sera which reacted with bovine serum albumin. Thus, Avitene was the most immunogenic of the collagen materials examined, while GAX collagen demonstrated the greatest persistence and minimal immunogenicity, and ZCI was the least immunogenic.

Artecoll polymethylmethacrylate implant (Artecoll) is a combination of polymethylmethacrylate beads suspended in 3.5% atelocollagen and has been designed for use in soft-tissue augmentation applications. The biocompatibility and immunogenicity of Artecoll were evaluated to assess the safety of this product for use in the dermis. To characterize the collagen component, chemical analysis was performed including trypsin sensitivity, differential scanning calorimetry, and pepsin content. Particle size analysis was also performed on the polymethylmethacrylate beads. The ability of this material to elicit an immunologic response was measured in a sensitized and nonsensitized guinea pig intradermal model. In these studies, 24 guinea pigs were injected intradermally with either Artecoll or Zyderm, a bovine collagen product for soft-tissue augmentation. Six sites were evaluated for each material at 3, 7, and 28 days after injection. In the sensitized model, 60 guinea pigs were divided into five groups, and each group received a sensitizing dose (in conjunction with Freund's adjuvant) of Zyderm, Artecoll, or a nonsensitizing dose of the same materials. The fifth group served as a nontreatment control. After the animals were sensitized, they were challenged with intradermal injections of various antigens to evaluate delayed type hypersensitivity reactions. Chemical characterization indicated polymethylmethacrylate beads of varying sizes, including many less than 35 microns, and a vehicle of extensively denatured and impure collagen. In vivo evaluations indicated that Artecoll elicited an immune response in guinea pigs, including delayed type hypersensitivity and antibody reactions. Histological assessment demonstrated particle phagocytosis and transepidermal elimination. Following immunization with Artecoll, guinea pigs were also found to be sensitized to pepsin, an impurity found in the collagen carrier. The biocompatibility of this material was compared with that of bovine dermal collagen (Zyderm collagen implant), which is widely used and accepted as biocompatible. The results of this evaluation indicate that Artecoll polymethylmethacrylate implant has the potential to elicit an immune response in humans, and polymethylmethacrylate beads are susceptible to phagocytosis and elimination.

A randomized, controlled clinical study of the management of diffuse bleeding with CoStasis surgical hemostat, a new hemostat containing bovine thrombin and collagen with the patient's own plasma, included patients undergoing cardiac, hepatic, iliac, and general surgery. Sera from 92 patients treated with CoStasis and 84 control patients were collected preoperatively and at a post surgical follow-up of 8 weeks. Among the control group, 57 patients were treated with Instat collagen sponge in noncardiac indications. Results showed that antibody responses in the CoStasis clinical study were similar to the reported literature for all antigens screened and were not associated with any adverse reactions. The bovine thrombin preparations in CoStasis and other commercially available thrombins were compared with the use of SDS-PAGE and Western blot analyses. Within this clinical study, CoStasis was shown to be a safe and effective hemostatic product containing bovine thrombin and bovine collagen and no pooled human blood products.