Biomimetic peptides in bone tissue engineering: From function to application

Current treatments for bone diseases are facing significant limitations, including adverse side effects, high costs and safety concerns. Surgical interventions and biologics (e.g., BMP-2) also present challenges in terms of complications, immunogenicity, and spatiotemporal control. Bone tissue engineering (BTE) uses biomaterials (e.g. hydroxyapatite, biodegradable polymers, hyaluronic acid) to provide structural support and ensure biocompatibility. However, these materials exhibit certain drawbacks, including mismatched degradation rates, inadequate mechanical strength, limited bioactivity, and an inability to dynamically regulate healing phases. Biomimetic peptides are synthetic short-chain amino acids that have been engineered to replicate functional domains of natural proteins. They offer low immunogenicity, design flexibility, and high functional specificity. In this review biomimetic peptides were categorized into the following groups based on their function: osteogenic peptides, cell adhesion peptides, antimicrobial/anti-inflammatory peptides, cell penetrating peptides, angiogenic peptides, and peptides targeting bone or cartilage. These peptides have been shown to synergize with biomaterials through covalent coupling, self-assembly or adsorption. Peptide-modified biomaterials can be influenced by binding mode, peptide structural sequence, spatial arrangement, and substrate properties. However, the clinical translation of biomimetic peptides faces challenges such as peptide instability, low oral bioavailability and the need for scale-up production. It is reassuring that current innovations in peptide cyclization, such as cyclic RGD peptides, delivery systems (e.g., dynamic hydrogels, PLGA microspheres) and multifunctional designs (e.g., bifunctional fusion peptides) hold promise. Future advances in biomimetic peptides will depend on interdisciplinary collaborations to optimize peptide-scaffold interactions, spatiotemporal release kinetics, and regulatory pathways for regeneration.