dECM HYDROGELS FOR SUPPORTING NERVE REGENERATION

Peripheral nerve injury is a clinical condition that severely reduces patient quality of life by damaging sensory and motor functions. In the last decades, tissue engineering has developed a variety of materials that can promote the regeneration of peripheral nerves in case of severe nerve damage. Among these, due to their ability to preserve tissues native environment, stimulate the proliferation and migration of Schwann cells (SC), and provide cues for nerve regeneration, Extracellular matrix (ECM) hydrogels could be a significant advancement in nerve regeneration support systems. The aim of the present study is to define the possible role of a human decellularized extracellular matrix (dECM) in sustaining peripheral nerve regeneration in vitro and then ex vivo, in order to develop an innovative strategy in the field of nerve repair. The dECM tested in this study is derived from cadaver human skin and underwent a decellularization protocol to obtain a dECM hydrogel. It was tested in vitro on neuronal (NSC34) and glial (RT4-D62PT) cell lines and on primary Schwann cell culture. Proliferation assay was performed on RT4-D62PT SC cell line, using dECM in solution, while primary SC have been cultured to analyze its role in promoting migration, with promising results. To study the interactions of neurons with the extracellular molecules and to evaluate neurite orientation and outgrowth, NSC34 cells were seeded on coverslips coated with dECM, differentiated after 3 days of culture in order to quantify the neurites number and length. The preliminary results showed that this matrix has a significant impact on the proliferation and migration of glial cells, and on axonal sprouting and elongation of motor neurons. The dECM hydrogel will be tested also ex vivo on dorsal root ganglia (DRG) and autonomic explants to obtain a multicellular structure that provides a closer approximation to in vivo conditions. Further investigations are underway to deepen the effect of the dECM in the activation of molecular pathways related to peripheral nerve regeneration.