Bone regeneration utilizing a newly developed octacalcium phosphate/weakly denatured collagen scaffold

Abstract

Introduction: Autologous bone grafting or various bone-regenerating materials are used to treat bone defects caused by tumor resection and accident trauma. Octacalcium phosphate, a reasonable bone regenerative material, activates osteoblasts. We fabricated a composite material, octacalcium phosphate/weakly denatured collagen, as a new scaffold. We aimed to investigate the osteoregenerative effect of the octacalcium phosphate/weakly denatured collagen scaffold (compared with that of weakly denatured collagen) in skull defects in a canine model. Methods: Atelocollagen was extracted from porcine skin via pepsin treatment. The weakly denatured collagen scaffold was fabricated with a freeze-dried and thermally crosslinked atelocollagen suspension at pH 7.4. Octacalcium phosphate was synthesized using Ca-acetate and NaH2PO4. Octacalcium phosphate particles (diameter, 199–298 µm) were mixed with a collagen matrix to fabricate an octacalcium phosphate/weakly denatured collagen scaffold. Bilateral defects (diameter, 10 mm; full-thickness) were induced in dog skulls, and the octacalcium phosphate/weakly denatured collagen and weakly denatured collagen scaffolds were implanted into the defects. Results: Eight weeks after implantations, bone regeneration was evaluated via histopathological analysis. It revealed osteoblast infiltration and osteoregeneration in all defects treated with the octacalcium phosphate/weakly denatured collagen scaffold. The defects treated with weakly denatured collagen scaffold or without any scaffold mostly contained connective tissue, with no neo-osteogenesis. Discussion: The novel octacalcium phosphate/weakly denatured collagen scaffold better promotes osteoregeneration than the weakly denatured collagen scaffold; this “in situ tissue engineering” approach is potentially clinically applicable for bone reconstruction.