3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth supported enhanced by factor cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected critical sciatic damage (12-mm gap) divided into sham, autograft, PCL (empty NGC), + MSCs (NGC multi-functionalized 10 6 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro , the characterized directly stimulated interferon-gamma evaluate their neuroregeneration potential. vivo tibial functional indices evaluated 12 weeks. Gait analysis conduction velocity analyzed after 8 Morphometric was performed weeks following lesion development. Real-time PCR neurotrophic factors BDNF, GDNF, HGF, cytokine IL-10. Immunohistochemical p75 NTR receptor, S100, neurofilament nerve. Results The inflammatory environment have increased expression neurotrophins IL-10 AdMSCs. HFB improved electrophysiological recovery compared group However, results not significantly different than those obtained using autografts. These findings associated a shift regeneration process towards formation myelinated fibers. Increased immunostaining receptor upregulation HGF spinal cord group. A trend demonstrating higher reactivity Schwann branching observed, engrafted at 30 days repair. Conclusions NGCs biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports trophic microenvironment, resulting pro-regenerative state injury rats.