Peptide Therapeutics in Orthopaedics: Current Evidence and Future Directions.

➢ Peptides lack a rigid tertiary structure, allowing them to adopt a variety of conformations, and can be engineered for specific targets. This article examines the design principles underlying orthopaedic peptide applications, from preclinical candidates to clinically validated drugs. ➢ The use of peptides in orthopaedics began with naturally occurring agents, such as bone morphogenetic proteins, and has evolved toward rationally engineered synthetics. ➢ Teriparatide, a synthetic parathyroid hormone-derived peptide, is used for bone regeneration; PLG0206, a fully engineered antimicrobial peptide, has demonstrated activity against biofilm-forming and multidrug-resistant organisms that conventional antibiotics cannot eradicate, and is advancing through Phase-II and III clinical evaluations. ➢ Peptide engineering has produced candidates with potential for cartilage-penetrating, sustained local drug delivery, although no peptide-based disease-modifying osteoarthritis drug has yet achieved clinical validation. ➢ Artificial intelligence-driven peptide design is accelerating discovery, but the translation of computationally designed sequences to clinical efficacy remains an active challenge.