Bonegraft Using Octacalcium Phosphate Collagen Composite with Teriparatide and Polylactic Acid Cage

Abstract

Octacalcium phosphate (OCP) is a bone grafting material known for its biocompatibility, osteoconductive, and osteogenic properties. Current treatments for extensive jaw defects often involve vascularized bone grafts or titanium mesh-based osteogenesis, which have limitations such as graft resorption, infections, and reoperation needs. In this study, a new bone regeneration therapy was explored, in which OCP combined with collagen (Col), treated with teriparatide (TPTD), was encased in a polylactic acid (PLA) cage to enhance structural stability and promote controlled bone formation. The therapeutic effects of this approach were evaluated using a rat model for calvarial regeneration, employing immunohistochemical staining. TPTD-treated OCP/Col composites were encased in cylindrical PLA cages, which were created using a 3D printer, and implanted into rat skulls. Three cage designs were tested: no holes, one large hole, and several small holes. Following implantation, the specimens underwent microcomputed tomography (micro-CT), histological, and immunohistochemical analyses to assess bone regeneration. In the micro-CT analysis, radiopacity at the OCP/Col graft site was higher in the “no hole” cage group than in the other groups from 4 to 12 weeks after implantation, particularly in the marginal area and region adjacent to the bone. Histological analysis revealed that, in all groups, new bone formation was observed along the surface of the skull 12 weeks postimplantation. In the “no hole” cage group, bone formation extended to the upper middle section, and bone matrix was present in areas where mature bone formation was lacking. In the other two groups, fibrous tissue filled the holes in the PLA cage, and no bone formation was observed directly beneath the holes. Immunohistochemical analysis revealed the expression of osteopontin, osteocalcin, runt-related transcription factor 2, vascular endothelial growth factor, and collagen I in all groups. The “no hole” cage group exhibited uniform and successful bone formation, with these cell markers consistently observed throughout all regions. These results suggest that using PLA cages to cover TPTD-treated OCP/Col discs effectively promotes bone regeneration. This approach provides a promising alternative to conventional bone grafting techniques and may help overcome the limitations associated with free or autologous bone grafts in oral and maxillofacial reconstruction.

Impact Statement

This study demonstrates that encasing teriparatide-treated octacalcium phosphate/collagen composites in polylactic acid (PLA) cages enhances bone regeneration. Using a rat model, microcomputed tomography, histological, and immunohistochemical analyses revealed that the “no hole” PLA cage design promoted uniform and successful bone formation, whereas perforated cages led to fibrous tissue infiltration. These findings highlight the potential of PLA cages in optimizing bone grafting strategies, offering a promising approach for tailored bone regeneration therapies.