Collagen membranes are widely used in guided bone regeneration (GBR) because of their good biocompatibility and low immunogenicity. As a bioderived collagen membrane, small intestinal submucosa (SIS) has good regenerative potential for soft tissue repair, but it lacks sufficient mechanical properties for GBR application unless properly modifided. Epigallocatechin-3-gallate (EGCG) is a natural cross-linking agent featuring osteoinductive activity. In this study, we modified SIS by EGCG cross-linking, and such modified materials were characterized both in vitro and in vivo. The results showed that EGCG cross-linking significantly improved the mechanical properties and hydrophilicity of SIS while maintaing good cytocompatibility. Compared to SIS, EGCG-cross-linked SIS (E-SIS) enhanced the adhesion of fibroblasts and preosteoblasts and promoted the osteogenic differentiation of MC3T3-E1 cells cultured on the materials. In a rat cranial defect model, E-SIS material showed better occlusion effect than SIS material. Most importantly, E-SIS material accelerated bone regeneration more than SIS material and even a commercially available GBR membrane. Taken together, we conclude that E-SIS is a promising material as a GBR membrane.
Keywords: cross-linking; epigallocatechin-3-gallate; guided bone regeneration; osteogenesis; small intestinal submucosa.