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Chitosan Tubes for Peripheral Nerve Regeneration
Giulia Ronchi, PhD1; Stefania Raimondo, PhD1; Giovanna Gambarotta, PhD1; Benedetta Elena Fornasari, BSC1; Alessandro Crosio, MD2; Pierluigi Tos, MD; PhD3; Bruno Battiston, MD2; Thomas Freier, PhD4; Kirsten Haastert-Talini, PhD5; Claudia Grothe, PhD5; Stefano Geuna, MD1
1University of Turin, Orbassano, Torino, Italy, 2Microsurgery Unit, CTO Hospital, Torino, Italy, 3UO di microchirurgia ricostruttiva, Ospedale Gaetano Pini, Milano, Italy, 4Medovent GmbH, Mainz, Germany, 5Hannover Medical School, Hannover, Germany
Introduction: Recent studies demonstrated that the chitosan guides used for peripheral nerve repair showed results similar to those obtained using autologous nerve grafts after immediate repair of rat sciatic nerve gaps. These promising pre-clinical results led to approval of the chitosan tubes for clinical use in 2014 as ReaxonŽ Nerve Guide. In this study we show a strategy to further improve the performance of the chitosan tube by the introduction of longitudinal skeletal muscle fibers. As previously demonstrated, muscle fibers used to fill a vein ("muscle-in-vein" conduit) improve peripheral nerve regeneration when used to bridge a nerve defect up to 2cm.
Materials & Methods: The rat median nerve was repaired by means two different conduits: (i) 10 mm hollow chitosan tube; (ii) 10 mm chitosan tube enhanced by the introduction of skeletal muscle fibers (a longitudinal piece of the pectoralis major muscle was introduced inside the tube, muscle-in-tube). 10 mm autologous nerve graft was used as a positive control. Samples were harvested at both early (7, 14, 28 days after nerve repair) and late time points (3 months), and functional, morphological, stereological and biomolecular analysis were carried out.
Results: The biomolecular analysis carried out on early time points shows that the muscle inside the tube produces and releases neuregulin1, a key factor for the survival and activity of Schwann cells usually released following nerve injury. Indeed, neuregulin1 is also expressed in the autologous nerve graft, but is not detectable in the hollow chitosan tube, suggesting that the presence of the muscle compensates this lack. Moreover, the morphological analysis shows that few fibers are already present after 14 days from nerve repair only in the muscle-in-tube conduit.
Conclusions: These preliminary results are very promising, because they combine the simplicity and rapidity of the use of the chitosan tube, with the effectiveness of the muscle fibers to promote axon regeneration. From the clinical point of view, this conduit might be used instead of the autologous nerve graft which, although still considered the "gold standard" technique, has some well known disadvantages.
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