Laboratory of Human Anatomy
Lesions of the nerve structure result in a decreased or a complete loss of sensitivity and/or motor activity in correspondence of the innervated territory. Although peripheral nerve fibres retain a considerable regeneration potential also in the adulthood, recovery is usually rather poor, especially in case of large nerve defects. The poor outcome can be attributed to many factors, including the lesion site, the interval of time between the injury and the surgical repair, the inability of denervated muscle to accept reinnervation and to recover from muscle atrophy, the reduced ability of injured axons to regenerate after a long axotomy and the loss of the Schwann cell capability to support regeneration.
The research activities of our research group focus on different aspects of peripheral nerve repair and regeneration:
i) biological processes that regulate peripheral nerve regeneration following traumatic nerve events: one of our aims is to better understand the biological processes implicated in nerve degeneration and regeneration in order to identify possible therapeutic strategies that stimulate the regeneration rate of nerve fibers and their subsequent maturation;
(ii) different surgical techniques that improve the success of regeneration: these studies are done in close collaboration with the microsurgery teams, because they have direct contact with the patient;
iii) biomaterials compatibility for nerve prosthesis constitution: our research group deals with the investigation of new bioengineered and biomimetic graft materials for the repair of segmental nerve defects as a powerful alternative to autografts, and the development of new bio- and micro/nano-delivery systems of biomolecules stimulating nerve fiber regeneration;
iii) analyzing the changes in genes/proteins expression levels during the process of nerve degeneration and regeneration: in close collaboration with the Cellular and Molecular Biology Group, we focus our biomolecular research on the role of NRG/ErbB system during peripheral nerve injury and repair, because it is involved in the different stages of degeneration / regeneration / remyelination.
iv) Study of muscle response to denervation/reinnervation: we are also interested in the study of the prevention of denervated-muscle atrophy because, in addition to the damage occurring at the nerve level, trauma to the mixed peripheral nerves induces a denervation-related atrophy of the distal target skeletal muscles and therefore it is necessary to identify therapeutic strategies to maintain muscle trophism while motor nerve fiber regenerate and re-innervate the muscle target.
Ronchi G, Cillino M, Gambarotta G, Fornasari BE, Raimondo S, Pugliese P, Tos P, Cordova A, Moschella F, Geuna S. Irreversible changes occurring in long-term denervated Schwann cells affect delayed nerve repair. J Neurosurg. 2017 Oct;127(4):843-856.
Mazzara PG, Massimino L, Pellegatta M, Ronchi G, Ricca A, Iannielli A, Giannelli SG, Cursi M, Cancellieri C, Sessa A, Del Carro U, Quattrini A, Geuna S, Gritti A, Taveggia C, Broccoli V. Two factor-based reprogramming of rodent and human fibroblasts into Schwann cells. Nat Commun. 2017 Feb 7;8:14088.
Fregnan F, Ciglieri E, Tos P, Crosio A, Ciardelli G, Ruini F, Tonda-Turo C, Geuna S, Raimondo S. Chitosan crosslinked flat scaffolds for peripheral nerve regeneration. Biomed Mater. 2016 Aug 10;11(4):045010.
Meyer C, Stenberg L, Gonzalez-Perez F, Wrobel S, Ronchi G, Udina E, Suganuma S, Geuna S, Navarro X, Dahlin LB, Grothe C, Haastert-Talini K. Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves. Biomaterials. 2016 Jan;76:33-51.
Moimas S, Novati F, Ronchi G, Zacchigna S, Fregnan F, Zentilin L, Papa G, Giacca M, Geuna S, Perroteau I, Arne ZM, Raimondo S. Effect of vascular endothelial growth factor gene therapy on post-traumatic peripheral nerve regeneration and denervation-related muscle atrophy. Gene Ther. 2013 Oct;20(10):1014-21.