3D Bioactive Scaffolds with Synergistic Non-biochemical Cues for Peripheral Neural Regeneration

Research output: Book/anthology/dissertation/reportPh.D. thesisResearch

Peripheral nerve injurie (PNI) is a serious condition that can result in function loss and thus calls for effective treatment. As an alternative to autologous nerve graft, implantable nerve guidance conduits (NGCs) have been widely investigated for the regeneration of large injury gaps (>20 mm). Biochemical cues such as neurotrophic factors are widely incorporated for promoting neurogenesis, while cellular behaviors can also be modulated by various other non-biochemical factors imposed by their surrounding microenvironment. This project aims at developing novel bioactive scaffolds for peripheral neural regeneration, in which dual non-biochemical cues (i.e. indirect electrical stimulation and anisotropic topography) are introduced to synergistically promote the regeneration. In the first attempt, composite scaffolds composed of electrospun PCL/gelatin fibers with surface coating of graphene family nanomaterials were prepared, which both maintain the extracellular matrix (ECM) mimicking architectures from the electrospun membrane and display conductive features for transferring electrical signals. Further decorating the surfaces with graphitic carbon nitride (g-C3N4) enabled an indirect electrical stimulation (named as photocatalytic stimulation) to the cells. The g-C3N4 nanoparticles were found biocompatible to PC12 cells, and led to ~18.5-fold increase in neurite extension after 11 days of differentiation under visible light irradiation (450 nm). Further, anisotropic topographical guidance was incorporated into the design by melt-electrospinning writing (MEW). Patterned architectures such as square, rectangular and parallelogram patterns were investigated. Here it was observed that changing the spacing ratio between the two arms of patterns led to preferential neurite extension on the long arm of these anisotropic patterned scaffolds. Moreover, through changing the angles of the intersections (30°, 45°, 60° and 90°), neurite extension generally adapted to the topographic change of the scaffold. Quantitative data revealed that along with decreased angle, further focused and extended neurites were obtained. Thus, through tailoring the fiber spacing and angle of the intersections, the scaffold provided topographic guidance for dominant neurite extension in specific direction. Finally, two construction strategies were explored for assembling these scaffolds into NGCs for peripheral nerve regeneration. Among them, a template based strategy was used as a straight-forward method to fabricate the NGCs with tailorable inner diameter and luminal thickness via controlled template sizes. The self-crimping strategy relied on an underneath thermo-responsive PNIPAM membrane that initiated the crimping process around body temperature with the promise for a smart spontaneously-forming-upon-implantation in clinical application.
Original languageEnglish
PublisherAarhus Universitet
Number of pages116
Publication statusPublished - Nov 2019

Note re. dissertation

Defence date: 18-11-2019

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ID: 163580981