Multidisciplinary characterization of human amniotic membrane: supporting translational applications in nerve surgery

Background. The most severe peripheral nerve injuries (PNIs), classified as neurotmesis, represent a significant cause of functional disability and neuropathic pain due to the inadequacy of physiological repair processes. Despite the remarkable advances in reconstructive microsurgery, the formation of neuromas, fibrosis, and perineural adhesions at the injury site continues to represent one of the main obstacles to axonal regeneration and functional recovery. In this context, the human amniotic membrane (hAM) has attracted increasing interest owing to its anti-inflammatory, immunomodulatory, anti-fibrotic, and pro-regenerative properties. Aim of the Study. The aim of this study was to characterize the human amniotic membrane through a multidisciplinary approach, evaluating its biological, structural, and biomechanical features of interest for its potential use as a biomaterial in peripheral nerve surgery and for future translational applications. Materials and Methods. Morphological, ultrastructural, histological, and biochemical analyses of hAM were performed. The identified properties were subsequently evaluated in vivo using two animal models of sciatic nerve neurotmesis followed by surgical repair. In particular, the effect of applying an amniotic membrane wrap in association with direct neurorrhaphy and autologous nerve grafting was investigated, these being considered the gold standard techniques for injuries without a gap and for those characterized by tissue loss, respectively. The results obtained were interpreted considering current knowledge regarding the mechanisms of peripheral nerve regeneration and the biological strategies aimed at limiting the formation of adhesions and perineural fibrosis. Results. The human amniotic membrane exhibited characteristics favorable to its use as a "biological neuroprotector" in nerve surgery, including high biocompatibility, abundance of extracellular matrix components, the presence of bioactive factors involved in tissue repair processes, and mechanical properties suitable for supporting the reconstruction site. This was reflected in the in vivo models by more effective muscle reinnervation and reduced formation of perineural adhesions at the surgical site. Overall, the collected evidence suggests that hAM can modulate the local microenvironment and contribute to the reduction of the fibrotic response following nerve injury. Conclusions. Although further preclinical and clinical studies are required to accurately define its efficacy, application modalities, and therapeutic indications, human amniotic membrane represents a promising biological strategy for the development of regenerative approaches aimed at improving the outcomes of peripheral nerve repair.