Independent effects of structural optimization and resveratrol functionalization on extracellular matrix scaffolds for bone regeneration

Abstract

Due to their natural biological activity and low immunogenicity, decellularized extracellular matrix (ECM) materials have aroused interest as potential scaffold materials in tissue engineering. Decellularized small intestinal submucosa (SIS) is one ECM biomaterial that can be easily sourced. In the present study, we tested whether the osteogenesis of SIS scaffolds was enhanced via structural optimization and resveratrol (RSV) functionalization and explored the independent effects of these modifications. We obtained SIS scaffolds with different pore structures by controlling the preparation concentration. The group with superior osteogenic properties was further RSV-functionalized via covalent immobilization. We conducted a series of in vitro and in vivo studies to explore the effects of these two optimization strategies on the osteogenic properties of SIS scaffolds. The results showed that pore structure and RSV functionalization significantly affected the osteogenic properties of SIS scaffolds. With a fabrication concentration of 1%, the SIS scaffolds had superior osteogenic properties. Through covalent coupling, RSV was successfully grafted onto SIS scaffolds, where it was slowly released. The most significant improvements in osteogenic properties were obtained with a coupling concentration of 1%. Furthermore, in in vivo experiments, vascular and new bone tissue formation was enhanced with RSV/SIS scaffolds compared with SIS scaffolds and the blank control group at 4 weeks after implantation. These findings indicate that the RSV/SIS scaffolds obtained via dual optimization strategies show promise as biomaterials in bone tissue engineering.