Matrillin-2 with K-Chitosan Scaffold Enhances Functional Recovery and Nerve Regeneration in a Segmental Rat Sciatic Nerve Injury Model

Background/Objectives: Previous work in our lab demonstrated that a 3D scaffold containing lysine-modified chitosan (K-chitosan) and decorated with Matrilin-2 (MATN2) enhances Schwann cell (SC) migration and axonal outgrowth in vitro and ex-vivo. This study aimed to assess the regenerative effect of this scaffold compared to a collagen conduit and autograft using a segmental rat sciatic nerve injury model. Methods: 30 Lewis Rats were assigned to three groups: untreated collagen conduit (UC), collagen conduit treated with MATN2 K-chitosan (TC), and reverse autograft (RA). Walking force measurements, compound muscle action potential (CMAP), wet muscle weight of the tibialis anterior and gastrocnemius, and axonal histomorphometry were assessed. Results: Walking force and CMAP were significantly higher in the TC group compared to the UC group (p=0.0035 and p=0.044, respectively), with no significant difference between TC and RA groups. Muscle weights were significantly greater in the TC group compared to UC (p=0.0202) but smaller than RA (p=0.003). The TC group resulted in significantly greater axonal regeneration compared to UC (p=0.0331) and no differences with RA (p=0.994). TC further demonstrated significantly greater cell counts than UC (p=0.0074) and greater Schwann cell affinity towards nerve reconstruction (p=0.0064). Conclusion: The MATN2 K-chitosan scaffold significantly improved nerve regeneration and was comparable to the RA group, supporting the development of a novel bio-conductive scaffold conduit.