Bone regeneration, tendon fiber formation, and angiogenesis are enhanced by the multifaceted effects of biodegradable octacalcium phosphate and gelatin scaffold materials

Abstract

The concept is highly attractive from the perspective of biomaterials science and tissue engineering: if a single material can act diversely on several cell types, promoting the regeneration of their respective tissues. The studies have shown that octacalcium phosphate (OCP) activates various bone-related cells, including osteoblasts, osteocytes, osteoclasts, mesenchymal stem/stromal cells, macrophages, myoblasts, tendon stem/progenitor cells, and endothelial cells. It is known that OCP (Ca₈H₂(PO₄)₆·5H₂O) cannot be sintered while maintaining its single crystal phase due to the inclusion of a large amount of water molecules. The brittleness of OCP and its handling property, however, can be improved by utilizing tissue-derived polymers such as gelatin as a matrix material. OCP/gelatin composite, in fact, enhances transcortical standardized bone defect repair in rat femur, rotator cuff tendon insertion (enthesis) in rabbit, and angiogenesis prior to bone regeneration in rat critical-sized calvaria defect. The undecalcified tissue histomorphometry of the rat femur transcortical defect found that OCP/gelatin implantation induced woven bone formation, which is a precursor of mineralized bone formation, compared to a highly porous resorbable material, β-tricalcium phosphate (β-TCP). This study investigates the multifaceted effects of OCP by focusing on its activating effects on cells derived from several different bone-related tissues.

Statement of significance

The regeneration of tissues, including bone and enthesis, is being vigorously pursued using a combination of cells, growth factors, and biomaterials, yet it continues to be a significant challenge. OCP has been advocated as a precursor of bone apatite crystals and has recently been recognized as a promising osteoconductive and biodegradable biomaterial that has attracted attention. Since OCP has been shown to exhibit pleiotropic cell activation capabilities across several cell types, proposing a new principle in biomaterials science would be possible if OCP-based materials prove effective in the regeneration of multiple tissues. This review article summarizes the multifaceted cellular activity and tissue regenerative capacities, including enthesis and vascularization, as well as new bone formation using OCP, particularly in combination with gelatin, a thermal denaturation product of collagen.