Polyphenols and recombinant protein activated collagen scaffold enhance angiogenesis and bone regeneration in rat critical-sized mandible defect

Abstract

Background & Aim The health benefits of polyphenols (p-coumaric acid) due to its antioxidant effects are well known. In other hands, recombinant COMP-Ang1 a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent for tissue regeneration with increased angiogenics capacity. However, their combined functional roles as a processing cofactor in tissue engineering applications are less widely known. Polyphenols have been used to stabilize collagen and to improve its resistance to degradation in biological systems. Generation of harmful reactive oxygen species is one of the current problems in tissue engineering. Therefore, several studies to fabricate tissue replacement with the antioxidant capability to protect the replaced organ from free radicals have been reported. Further, multifunctional bone grafting biomaterials with both antioxidants and angiogenic properties have earned increasing interest in regenerative medicine. This study focuses on the functionality of antioxidant and angiogenic efficacy of p-CA and COMP-Ang1 to promote bone and vascular growth into biomaterials. Methods, Results & Conclusion Collagen scaffold were synthesized and loaded with p-CA and COMP-Ang1. Scaffold were divided into four groups-only scaffold, scaffold with p-CA, scaffold with COMP-Ang1 and scaffold with p-CA + COMP-Ang1.To evaluate the potential of each scaffold in bone regeneration, a critical-sized defect was made at the mandible of Sprague-Dawley rats. The defects were filled with scaffold accordingly groups as mentioned above. At 2, 6 and 10 weeks post-implantation, bone growth around the defect was examined by histology and µCT. Results revealed that implanting a COMP-Ang1 plus p-CA impregnated scaffold into a bone defects synergistically enhanced the amount of new bone. Furthermore, osteoinductivity of the COMP-Ang1+ p-CA scaffold result in striking upregulation of osteogenesis-related molecules, including osterix, osteocalcin and osteopontin with increased expression of angiogenic molecules, like- fibroblast growth factor-2 and vascular endothelial growth factor compared with only COMP-Ang1 and p-CA activated scaffold. These findings demonstrate that combined grafting of COMP-Ang1 with p-CA promotes bone formation in mandible defects, which is coupled with enhanced osteogenesis and angiogenesis and provides new insights for developing bone substitutes for tissue engineering and regenerative medicine.