Degradable Microchannel Nerve Guidance Scaffolds for Central and Peripheral Nerve Repair - From Soft to Rigid.

Nerve regeneration;Spinal cord injury;Hydrogel;Polymer;Mechanical testing;Cell attachment;Biomedical Engineering;Engineering;Macromolecular Science and Engineering

Shahriari, DenaTuszynski, Mark H ;

University of Michigan

关键词: Nerve regeneration;    Spinal cord injury;    Hydrogel;    Polymer;    Mechanical testing;    Cell attachment;    Biomedical Engineering;    Engineering;    Macromolecular Science and Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/133319/sdena_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Traumatic nerve injury is generally permanent and debilitating. There is no available therapy primarily owing to the lack of spontaneous axon growth in the adult human central nervous system. In this doctoral work, an interventional technology was investigated to promote and guide axons through nerve gaps to provide nerve repair.Previously, agarose hydrogel microchannel scaffolds linearly guided axons through lesion gaps of spinal cords in rats. However, these scaffolds were non-degradable. In this work, first the efficacy of degradable hydrogels such as alginate, chitosan and poly(ethylene glycol) (PEGDA) as nerve guidance scaffolds was studied. All the hydrogels, however, were concluded unstable in vivo and provided limited axon growth.To fabricate scaffolds effective for nerve repair poly caprolactone (PCL) with slow degradation rate (reported over 8 months) was selected and investigated. In addition, to increase the open volume of scaffolds, a novel scaffold architecture and fabrication process were introduced in which, both the channels open space and the interstitial space between the channels could be utilized for axon growth. A salt-leaching process was developed to optimize PCL properties such as porosity, stiffness and cell adhesion. The scaffold design entailed the fabrication of PCL tubes and their assembly inside a PCL outer tube resulting scaffolds with >60% open volume (a 3-fold improvement to state-of-the-art microchannel scaffolds). When implanted in transected spinal cords in rats, linear axon growth inside and between the channels was observed. The PCL scaffolds, with 3 orders of magnitude higher stiffness than the nerve tissue, provided the highest axon integration and growth in close proximity to the scaffold walls when compared to soft hydrogels. This observation is contradictory to the general belief that an implant with stiffness more closely matching the tissue is more effective. Indeed, this doctoral work is the first study that suggests axon/implant integration is enhanced in vivo when the substrate stiffness is orders of magnitude higher than the host tissue. This technology was translated to poly lactic-co-glycolic acid (PLGA), for a higher degradation rate, and was fabricated to clinically-relevant dimensions. Overall, this dissertation introduces a promising microchannel scaffold for its translation to human nerve repair.