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Extracellular matrices derived from animal tissues for human tissuerepairs are processed by various methods of physical, chemical, or enzymaticdecellularization, viral inactivation, and terminal sterilization. The mechanisms ofaction in tissue repair vary among bioscaffolds and are suggested to be associated withprocess-induced extracellular matrix modifications. We compared three non-cross-linked,commercially available extracellular matrix scaffolds (Strattice, Veritas, andXenMatrix), and correlated extracellular matrix alterations to in vivo biologicalresponses upon implantation in non-human primates. Structural evaluation showedsignificant differences in retaining native tissue extracellular matrix histology andultrastructural features among bioscaffolds. Tissue processing may cause both thecondensation 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 forStrattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrixmodifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibilityto collagenase degradation was increased in Veritas and XenMatrix when compared to theirrespective source tissues. Using a non-human primate model, three bioscaffolds werefound to elicit different biological responses, have distinct mechanisms of action, andyield various outcomes of tissue repair. Strattice permitted cell repopulation and wasremodeled over 6 months. Veritas was unstable at body temperature, resulting in rapidabsorption with moderate inflammation. XenMatrix caused severe inflammation andsustained immune reactions. This study demonstrates that extracellular matrixalterations significantly affect biological responses in soft tissue repair andregeneration. The data offer useful insights into the rational design of extracellularmatrix products and bioscaffolds of tissue engineering

Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration