Regenerative peptides for inferior alveolar nerve injury: a narrative review

Inferior alveolar nerve (IAN) injury is a clinically important complication of oral and maxillofacial procedures that can lead to persistent neurosensory impairment, and effective regenerative interventions are presently scarce. This narrative review assessed the mechanistic rationale, preclinical evidence, translational limitations, and potential future relevance of regenerative peptides for IAN repair. Particular attention is given to BPC-157, thymosin β 4 (T β 4) and its related synthetic fragment TB-500, and ARA-290 (cibinetide), whose reported biological functions intersect with primary mechanisms implicated in peripheral nerve regeneration, such as cellular survival, Schwann cell activity, inflammatory modulation, angiogenesis, extracellular matrix remodeling, and axonal regeneration. Nevertheless, the available evidence is mainly sourced from pre-clinical and non-IAN systems, and direct evidence of efficacy in iatrogenic or traumatic IAN injury remains inadequate. BPC-157 and TB-500 remain investigational compounds with important safety, pharmacokinetic, and regulatory uncertainties, whereas evidence associated with TB-500 should be differentiated from that obtained with full-length T β 4. Translation to IAN injury is further complicated by the lack of validated local delivery approaches, uncertain target-site pharmacokinetics, the anatomically restricted mandibular canal, and injury severity. Potential combination strategies involving traditional therapies, biomaterial-assisted delivery frameworks, and dental stem cell-mediated regenerative approaches are mechanistically plausible but remain hypothesis-generating rather than definitive synergistic interventions. Prospective research should prioritize IAN-relevant experimental systems, injury-severity classification, standardized outcome measures, target-site pharmacokinetics, and rigorously controlled clinical trials. Overall, regenerative peptides constitute a biologically plausible but currently investigational method for IAN repair, and their clinical application will rely on exhibiting reproducible efficacy and safety within indication-specific models and human trials.