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Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration
Authors:Yulia Berkovitch  Talia Cohen  Eli Peled  Robert Schmidhammer  Hildner Florian  Andreas H Teuschl  Susanne Wolbank  Dvir Yelin  Heinz Redl  Dror Seliktar
Institution:1. The Faculty of Biomedical Engineering, Technion‐Israel Institute of Technology, Haifa, Israel;2. The Interdisciplinary Program for Biotechnology, Technion‐Israel Institute of Technology, Haifa, Israel;3. The Faculty of Medicine, Technion‐Israel Institute of Technology, Haifa, Israel;4. Orthopedic Surgery Division, Rambam Health Care Campus and The Bruce Rappaport Faculty of Medicine, Technion‐Israel Institute of Technology, Haifa, Israel;5. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna, Austria;6. Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria
Abstract:Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi‐synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo‐patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser‐ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo‐patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.
Keywords:biomaterials  fibrinogen  hydrogels  micropatterning  nerve regeneration  nerve guidance conduit
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