Neuronal regeneration with novel polyvinyl alcohol/chitosan scaffold and stem cells in canine spinal cord injury model: from development to animal studies

Study Design: An experimental study on scaffold characterization and animal study. Purpose: To evaluate the neuroregenerative effects of a novel polyvinyl alcohol/chitosan (PVA/CS) scaffold and umbilical cord-derived mesenchymal stem cells (UC-MSCs) in canine spinal cord injury (SCI) models. Overview of Literature: Current SCI therapy mainly focuses on restoring mechanical stability without directly addressing its neuronal function. Although studies have shown that cell-based therapies can promote regeneration, their application remains limited due to poor cell survival and migration from target site after implantation. Hence, combining stem cells with scaffolds, which function as threedimensional homing materials, could potentially enhance their delivery and retention at the injury site. Methods: The mechanical profiles of the PVA/CS scaffold were analyzed, including its chemical group identification, fiber topography, and strength. Its biological profiles, namely its cellular viability and biodegradation were also evaluated. SCI models were created using the balloon compression method at the T10-T11 level on 12 selected canines, which were grouped into control (CD), mechanical intervention (IM), and mechanical + PVA/CS-UC-MSC intervention (SC) for further examination. Each canine was observed for 56 days to assess for clinical improvement using the canine Basso-Beattie-Bresnahan score and underwent histopathological evaluation using hematoxylin-eosin (HE) and Luxol fast blue (LFB) staining. Results: PVA/CS scaffold characterization showed excellent mechanical strength and biocompatibility profile. Our animal study showed significant motor improvement in the SC group compared to the other groups (pCD=0.037; pIM=0.012). This finding was supported by histopathological examinations in the SC group, which showed less intralesional hemorrhage on HE staining (pCD=0.020; pIM=0.016) and less demyelination of the anterior (pCD=0.020; pIM=0.016), lateral 1 (pCD=0.012; pIM=0.048), and lateral 2 (pCD=0.007; pIM=0.027) views of the spinal cord on LFB staining. Conclusions: PVA/CS scaffolds and stem cell therapy have the potential to promote neuroregeneration in conjunction with routine stabilization treatment for the comprehensive management of SCI.