Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration

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.

Applications of Engineering Techniques in Microvasculature Design

“…The degraded hydrogel is then flushed out of the construct to generate microchannels. Hydrogels used for laser degradation can be made from natural polymers such as silk (20), collagen (21,22) and elastin (22), synthetic polymers such as poly(ethylene glycol)diacrylate (PEGDA) (23), PEGtetrabicyclononyne (24) or composite materials such as polyethylene glycol (PEG)-fibrinogen (25). Incorporating natural polymers is crucial in providing cell-adhesion ligands for cell-matrix interactions and biochemical signaling in the microenvironment to induce angiogenesis postimplantation.…”

Natural-Based Biomaterials for Peripheral Nerve Injury Repair

“…Microstructured scaffolds might be useful to mimic bigger structures, such as the bands of Büngner, encouraging axonal regrowth during peripheral nerve regeneration (Bozkurt et al, 2012;Gnavi et al, 2015). Thanks to several manufacturing processes like laser surface texturing, chemical substances, plasma treatment, electrospinning or use of a mold, changes in roughness can be made for most of the available biomaterials (Kim et al, 2016;Berkovitch et al, 2018;Chen et al, 2019).…”

“…As well as for its high biocompatibility, fibrin can be used as a scaffold in tissue engineering thanks to its versatility, indeed its dissolving and coagulation characteristics can be modified by changing the dilution (Bensaïd et al, 2003;Fang et al, 2004). Thanks to fibrin adhesive characteristics, this type of conduit could be not sutured; nevertheless, a recent study demonstrated that sutureless nerve repair with fibrin conduit fails to maintain nerve connections due to poor mechanical stretch resistance (Wang et al, 2018b).…”

Application of fibrin-based hydrogels for nerve protection and regeneration after spinal cord injury

“…The distance between the channels was 200 μm, which also guided the hydrogel. It promotes uniform tissue propagation during nerve regeneration [ 100 ].…”