Enhancing Bone Tissue Regeneration—A Mechanistic and Comparative Study

This study explores the combined effects of RGD functionalization and host immune response on bone tissue regeneration. Hydroxyapatite (HAp) biomaterials, synthesized from sustainable resources, were combined with polycaprolactone (PCL) to design implantable scaffolds. hFOB cell-laden PCL/HAp scaffolds, functionalized with RGD-C (arginine-glycine-aspartate-cysteine) peptides and BMP-2 (bone morphogenetic protein-2), were subcutaneously implanted into immunocompromised (nude) and immunocompetent (C57) mice for 12 weeks. The quality of the regenerated bone in both mouse models was evaluated via histological studies (including H & E, alizarin red S, and trichrome staining), along with medical CT and micro-CT scans, and mechanical characterization. The ability of the regenerated bone tissue to support dental implants was also investigated by measuring the interfacial mechanical strengths of inserted dental screws. Histological and medical CT analyses show evidence of accelerated mineralization with RGD functionalization as early as the second week post-implantation. However, the synergistic effects of RGD-functionalization and host immune system enhance the mechanical properties over the 12-week period. Notably, higher toughness and elastic modulus in the C57 mice suggest more effective mineralization and a denser collagen network, supported by micro-CT measurements and histological results. The progressive increase in mechanical properties and improved visco-elastic properties are indicative of a successful, active remodeling process. The mechanical characterization emphasizes the structural and functional viability of RGD-functionalized PCL/HAp scaffolds, validating the scaffold design and role of the host’s immune response in tissue engineering. These findings have implications for the regeneration of high-quality bone suitable for dental implants in patients with significant alveolar bone loss.