Three commercially available porcine-derived biologic meshes were implanted in an Old World primate abdominal wall resection repair model to compare biological outcome as a predictor of clinical efficacy. Tissues were explanted over a 6-month period and evaluated for gross pathology, wound healing strength, mesenchymal cellular repopulation, vascularity, and immune response. In vivo functional outcomes were correlated with in vitro profile for each material. Small intestinal submucosa-based implants demonstrated scar tissue formation and contraction, coincident with mesh pleating, and were characterized by immediate and significant cellular and humoral inflammatory responses. Porcine dermal-based grafts demonstrated significant graft pleating, minimal integration, and an absence of cellular repopulation and vascularization. However, a significant cellular immune response surrounded the grafts, coincident with poor initial wound healing strengths. In vivo observations for the three porcine-derived mesh products correlated with individual in vitro profiles, indicating an absence of characteristic biochemical markers and structural integrity. This correlation suggests that in vivo results observed for these mesh products are a direct consequence of specific manufacturing processes that yield modified collagen matrices. The resulting loss of biological and structural integrity elicits a foreign body response while hindering normal healing and tissue integration.

The combination of a nondamaging process, successful removal of cells, and reduction of the xenogeneic alpha-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.

Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering.

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