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Therapeutic Peptides in Orthopaedics: Applications

Review Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions Omar F Rahman et al. J Am Acad Orthop Surg Glob Res Rev. 2026. Abstract Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactiv

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Study findings do not automatically establish clinical benefit, safety, dosing, or suitability for an individual.

Review

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions

Omar F Rahman et al. J Am Acad Orthop Surg Glob Res Rev. 2026.

Abstract

Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.

Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.

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Figures Figure 1

Mechanism of action of BPC-157. BPC-157 = body protection compound-157.

References

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Anand U, Bandyopadhyay A, Jha NK, Pérez de la Lastra JM, Dey A: Translational aspect in peptide drug discovery and development: An emerging therapeutic candidate. Biofactors 2023;49:251-269. - PubMed

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