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

Abstract

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.

Effect of low-temperature ethylene oxide and electron beam sterilization on the in vitro and in vivo function of reconstituted extracellular matrix-derived scaffolds

“…(12) High-energy radiation as well can alter proteins directly by cleaving the protein chains, or indirectly by causing the buildup of free radicals in the surrounding atmosphere which themselves react with the protein groups and change protein structure. (4, 13, 14) Because some studies have shown a lesser reduction of the in vitro mechanical properties of ECM-derived scaffolds after electron beam sterilization when compared to gamma irradiation, electron beam radiation is generally the preferred irradiation method for ECM-derived devices. (15) Still, when comparing low temperature ethylene oxide with electron beam sterilization, the former seems to have a lesser effect on the in vitro mechanical properties and protein structure of dermal sheep collagen.…”

The development of SERI® Surgical Scaffold, an engineered biological scaffold

“…Comparative studies of ADMs report differing biologic responses, ranging from mild‐to‐severe inflammation and scaffold remodeling to fibrous encapsulation . In one study comparing various human‐ and animal (porcine)‐derived ADMs, minimal neovascularization was noted at 20 weeks while rates of tissue ingrowth and tensile strength differed between ADM sources .…”

“…32 While neovascularization was reported by the first assessment at 4 months with TIGR Matrix, 31 mild-to-moderate evidence of vascularization was observed by the first assessment at 6 weeks with P4HB as a mesh or plug. 32 Comparative studies of ADMs report differing biologic responses, ranging from mild-to-severe inflammation 33 and scaffold remodeling to fibrous encapsulation. 34 In one study comparing various human-and animal (porcine)-derived ADMs, minimal neovascularization was noted at 20 weeks while rates of tissue ingrowth and tensile strength differed between ADM sources.…”

Biomaterials and structural fat grafting

“…The presence of the α-Gal epitope on porcine tissues has been associated with rapid rejection. 68 The use of Strattice for repair of incisional hernias in Yucatan pigs compared to primary closure showed that primary closure caused more scarring and bone hyperplasia along the incision line. 67 In addition, glycosaminoglycans are still present, indicating that Strattice retains key markers for the presence of relevant biochemical components.…”