Engineering Bioactive Factor Releasing Polymeric Scaffolds for Nerve Regeneration

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Spontaneous regeneration in the adult mammalian central nervous system is rare, minimal, and generally does not lead to substantial functional recovery. Tissue engineering strategies to promote nerve regeneration aim to provide an environment that is physically and chemically engineered to enhance tissue formation. Strategic design of this environment is crucial and is developed based on fundamental understanding of cellular responses to specific design parameters. Single channel and multiple channel porous scaffolds developed for nerve regeneration were fabricated by a gas foaming/particulate leaching process. The quantity of porogen incorporated with the polymer influenced the porosity and mechanical properties of the scaffold. A sustained in vitro protein release was observed, with the release rate controlled by the method of incorporation and the polymer molecular weight. The multiple channel scaffold, or bridges, were further investigated for spinal cord regeneration in a rat spinal cord hemisection model. Design parameters of the bridges were correlated to features of the regeneration process. Cells found within the bridge channels were aligned to the major axis of the channel. Infiltrated cells were identified as fibroblasts, macrophages, Schwann cells, and endothelial cells. Neurofilament staining revealed a preferential growth of the neural fibers within the bridge channels when compared to the pores. Design parameters, such as porogen size and channel diameter/configuration, affected the neural fiber growth within bridge channels. Next, bioactive factor releasing polymer bridges were developed, targeting two major barriers to spinal cord regeneration, the insufficient level of neurotrophin and the overwhelming presence of chondroitin sulfate proteoglycan (CSPG) at the injury site. Bridge processing conditions did not affect the activity of factors incorporated. Behavioral analysis of NT-3 loaded and empty bridges over 8 week found similar functional recovery for both groups, where the animals were capable of weight supported plantar stepping. Implantation of bridges loaded with chondroitinase ABC at the rat spinal cord injury site dramatically reduced the CSPG presence at the lesion site. The development of a polymeric scaffold capable of providing physical guidance and chemical stimuli has potential for spinal cord regeneration.

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  • 06/25/2018
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