Development of a Novel Collagenous Matrix Based on Tissue-Mimicking Advanced Collagen Aggregate Synthetically Cross-Linked with Biological Cross-Linkers, OCS, and β-ODAP for Wound Healing

In this paper, the novel tissue-mimicking advanced collagen aggregate (TA-CA) consisting of collagen fibers and collagen fiber bundles functionally cross-linked with dialdehyde chitosan (OCS) and dencichine (β-ODAP) was developed as an efficacious wound-healing device with hemostatic properties. The synergistic cross-linking effects of β-ODAP and OCS on TA-CA was systematically studied by taking OCS, glutaraldehyde (GA), genipine (GP), and β-ODAP as control groups. The results showed that the thermal stability, mechanical properties, hydrophilicity, enzyme resistance, and hemostatic properties of TA-CA modified by β-ODAP and OCS (OCS/β-ODAP-TA-CA) were significantly improved. Meanwhile, the MTT assay and CLSM observation showed that the OCS/β-ODAP-TA-CA scaffold presented no cytotoxicity, better cell proliferation, and enhanced viability of primary fibroblast. The OCS/β-ODAP-TA-CA scaffold was implanted into Sprague–Dawley rats to evaluate the ability to repair full-thickness skin wounds with respect to collagen cross-linked with OCS/β-ODAP (OCS/β-ODAP-Col) as control. The results revealed that OCS/β-ODAP-TA-CA scaffold could better accelerate the wound-healing process and more effectively promote bFGF, VEGF, and PFDF expression compared with OCS/β-ODAP-Col. Overall, this work contributed a new insight into the development of the TA-CA scaffold modified with OCS and β-ODAP with excellent biocompatibility and hemostatic properties, and it further confirmed TA-CA could serve as a better alternative source of collagens for biological applications.