Regenerative neurotization in breast reconstruction: biomaterials, nerve guidance, and emerging strategies for sensory restoration

Sensory deficit is among the most prevalent long-term morbidities in the post-mastectomy reconstructed population, with direct implications for quality of life, body image, psychosexual function, and patient safety. Routine sacrifice of intercostal sensory nerves during mastectomy partially or completely denervates the breast skin and nipple-areola complex (NAC), producing numbness, paresthesia, and loss of protective sensation. Microsurgical neurotization, with or without nerve grafts, achieves clinically relevant sensory recovery in both autologous and implant-based reconstruction; meta-analytic evidence shows that neurotized flaps have superior tactile thresholds, faster recovery, and better protective sensation than non-neurotized flaps, although native sensation is not fully restored. Recovery is moderated by radiation history, regeneration distance, patient age, and surgical technique, and the field remains limited by donor-nerve availability, graft-related morbidity, cost, and the absence of standardized multimodal sensory assessment. Advances in regenerative medicine and biomaterials have introduced nerve guidance conduits, decellularized allograft scaffolds, extracellular matrix (ECM)-based conduits, neurotrophic factor delivery systems, and sutureless devices such as Nerve Tape (Biocircuit Technologies; Atlanta, GA), shifting emphasis from structural replacement toward biological restoration. This narrative review synthesizes clinical, translational, and mechanistic evidence on regenerative neurotization in breast reconstruction: it reviews peripheral nerve regeneration, appraises microsurgical neurotization and its comparative effectiveness, and evaluates regenerative adjuncts including biomaterial scaffolds, conduit-based repair, and molecular augmentation. A clinical translation framework is proposed, with sensory outcomes, methodological constraints, and future directions - smart biomaterials, artificial intelligence (AI)-assisted nerve mapping, and personalized regenerative reconstruction - identified as priorities for investigation.