Role of fresh skeletal muscle fibers in supporting vascularization and Schwann cell migration during peripheral nerve regeneration within a chitosan conduit

Authors:
Debora Molinaro (1), Federica Zen (1), Benedetta Elena Fornasari (1), Giulia Ronchi (1), Alessandro Crosio (1,2), Giovanna Gambarotta (1)

Organisations:
1: Department of Clinical and Biological Sciences (DSCB) and Neuroscience Institute Cavalieri Ottolenghi (NICO),University of Turin, Italy
2: Hand Surgery and Reconstructive Microsurgery Department, CTO, ASST Gaetano Pini, Milan, Italy

Presenting author:
Debora Molinaro

Exposition date:
Thursday, September 14, 2023 (Satellite Events Day)

Exposition position:
98

Peripheral nerve injuries are frequently encountered clinical complications which can lead to partial or complete impairment of sensory, motor and autonomic functions.

Several approaches have been developed to allow regeneration after nerve transection by bridging the gap between the two nerve stumps (tubulization). One of the neural guide conduits currently used in clinical practice is the chitosan tube, in which the formation of a polarized vasculature within the conduit acts as a scaffold for Schwann cell migration and axonal regrowth. Multiple pre-clinical studies have been focused on finding strategies to improve this technique; in particular, we investigated the enrichment of this conduit with fresh skeletal muscle fibers, which provide both trophic factors and physical support for Schwann cell migration.

Molecular analysis on the hollow chitosan tube (chitosan) and the conduit enriched with fresh skeletal muscle fibers (MIT, muscle-in-tube) at 7,14 and 28 days after repair displayed an increase in the expression of genes known to be positively involved in angiogenesis in the presence of skeletal muscle fibers, with a peak at 14 days after surgery.

Moreover, qualitative morphological analysis showed that, in the MIT, Schwann cells were associated with both blood vessels and muscle fibers, suggesting they might simply require an adequate physical substrate in order to migrate, instead of a specific protein-protein interaction.

A relevant difference in terms of nerve regeneration was detected at 14 days post-surgery between the MIT and the chitosan, with a slower progression of both vascularization and nerve regeneration in the MIT, where the abundant muscle tissue seemed to cause a delay in the first two weeks after surgery. On the contrary, no qualitative differences were observed between the two experimental models a month after repair. Further analyses will be carried out to obtain quantitative morphological results.