Retention of structural and biochemical integrity in a biological mesh supports tissue remodeling in a primate abdominal wall model

Abstract

Aim: Suboptimal clinical outcome following the implantation of porcine-derived tissue matrices may be due to the method of processing the material to achieve an acellular graft and to reduce the immune response to xenogeneic epitopes. The ability to produce a porcine-based graft material that retains the structural integrity of the extracellular matrix and minimizes the potential antigenic response to the galactose-α(1,3)-galactose terminal disaccharide (α-Gal) may allow the scaffold to support regeneration of native tissue. Materials & methods: Porcine dermal tissue was processed to remove cells and DNA, and minimize the presence of α-Gal via specific enzymatic cleavage. In vivo performance was evaluated by implantation into the abdominal wall of an Old World primate exisional repair model. Grafts were explanted at 0.5, 1, 3 and 6 months and assessed for cellular repopulation and vascularization, for localized immune response by presence of T cells, B cells and macrophages, and systemic immune response by anti-α-Gal IgG by ELISA. Results: Animals tolerated implants well and exhibited no clinical signs of inflammation, laxity, hernia or visceral tissue attachment. Histological evaluation revealed marked host fibroblast repopulation and neoangiogenesis as early as 2 weeks postimplant. Cellular repopulation and maturation of vascular structures reached a plateau at 3 months. Immunological evaluation of immune cell infiltration demonstrated an early, mixed cellular inflammatory response at 2 weeks. This cellular immune response was transient and diminished to baseline levels by 3 months postimplant. Conclusion: The combination of a nondamaging process, successful removal of cells, and reduction of the xenogeneic α-Gal antigens from the porcine dermal matrix, while maintaining an intact extracellular matrix, is critical to its ability to remodel and integrate into host tissue, leading to its overall acceptance.