Bioactive Microsurgery and CCL2: A Narrative Review of Immune Modulation Strategies for Peripheral Nerve Repair

Peripheral nerve injuries often result in incomplete functional recovery, despite technically successful microsurgical repair. Traditional strategies focus on structural continuity but neglect the immunobiological environment critical for regeneration. CCL2 (monocyte chemoattractant protein-1, MCP-1), a chemokine that coordinates macrophage recruitment and polarization, has emerged as a key regulator of neuroimmune responses involved in nerve healing. This narrative review evaluates the scientific rationale, preclinical evidence, and translational strategies for using CCL2 as a bioactive adjunct in peripheral nerve microsurgery. We synthesize findings from preclinical studies involving CCL2 in nerve injury models, including knockout and overexpression systems, graft integration, stem cell-based therapies, and pain modulation, with emphasis on delivery mechanisms applicable to intraoperative settings such as hydrogels, microsutures, and cellular approaches. Across multiple preclinical injury models, CCL2 has been shown to enhance macrophage-driven repair, promote angiogenesis, facilitate Schwann cell activity, and accelerate axonal regrowth. Loss of CCL2 signaling impairs functional recovery, whereas targeted delivery during the early regenerative window improves outcomes without evidence of prolonged inflammation. These studies further support hydrogels, microsutures, and mesenchymal stromal cell-based therapies as feasible platforms for CCL2 delivery. Together, these data support intraoperative CCL2 modulation as a novel, mechanistically grounded strategy to integrate immune biology with microsurgical technique. This bioactive approach has the potential to improve regeneration and graft integration while minimizing the risk of neuropathic pain through precise temporal and anatomic control of CCL2 delivery.