A review of biomimetic surface functionalization for bone-integrating orthopedic implants: Mechanisms, current approaches, and future directions

Orthopedic implants are increasing in global prevalence, with hundreds of thousands of operations performed annually. However, a significant proportion of these operations experiences failure due to poor bone integration. Many avenues of investigation have been explored to address this issue and improve the biocompatibility of orthopedic devices by modifying the biological response to the implant surface. Biomimetic functionalization of orthopedic surfaces enables control over the biological response by signaling through immobilized proteins and other biomolecules. This approach seeks to promote osteoblast differentiation and bone formation at the implant surface, leading to integration between the orthopedic surface and the local bone tissue. This review commences by highlighting the need for biomimetic functionalization from a materials and biological perspective. The surface properties that govern protein-surface interactions are subsequently explained. Progress in biomolecule functionalization of orthopedic surfaces performed via adsorption, chemical covalent immobilization, and physical covalent immobilization are discussed and reviewed. The immobilization mechanisms for each approach are examined and the strategies are evaluated according to their complexity, efficacy, reproducibility, and scalability. Emerging and prospective avenues for the transition from 2D to 3D substrates and the multi-functionalization of biomimetic surfaces are then explored.