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

Review · human · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026 · DOI 10.5435/JAAOSGlobal-D-25-00236 · PMID 41490200

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This review (species not specified) discusses therapeutic peptides as potential adjuncts in orthopaedic injury management, describing action on signaling pathways including PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK. It describes wound-healing peptides BPC-157, TB-500, and GHK-Cu as promoting angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, and growth hormone secretagogues ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 as activating IGF-1 signaling and satellite cell repair. Recovery-related peptides epithalon, delta sleep-inducing peptide, and pinealon are described as targeting circadian and mitochondrial regulators, while neuroactive peptides selank, semax, and dihexa are described as affecting brain-derived neurotrophic factor and HGF/c-Met pathways. The authors note that only preclinical studies currently exist, with no clinical trials reported, and frame this as a summary of mechanistic insight for musculoskeletal care.

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.

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