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Title: Combining novel biomaterial and growth-promoting strategies to promote spinal cord repair
Author: Varone, Anna
ISNI:       0000 0004 7972 545X
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2019
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Spinal cord injury (SCI) is a permanent and traumatic condition with no cure. The reasons for the regeneration failure are complex but they can be summarised in: poor intrinsic growth capacity of neurons, chemical and physical barrier. No single therapeutic approach for spinal repair has been successfully translated to the clinic so it is suggested that a combinatorial approach is more likely to be effective. An ideal treatment would be a tissue engineered scaffold in combination with a drug and a guidance cue to stimulate the regeneration. In this thesis, a meta-analysis was conducted demonstrating the validity of this approach. In fact, it was found that among all the published biomaterial-based studies, combination outcomes were consistently more effective than monotherapy with drugs, cells, or biomaterials alone. The experimental strategy for spinal repair investigated in this project consisted of: a biomaterial from Antheraea pernyi silkworm silk previously shown to support axon regeneration in peripheral nerve injury, omega-3 polyunsaturated docosahexaenoic acid (DHA) previously suggested to promote neurite outgrowth of rat dorsal root ganglion neurons, and direct current electric field (DC EF) earlier demonstrated to promote directional neurite growth in cultured non-mammalian or embryonic neuronal cells. These strategies were first investigated alone, mostly by using a model of postnatal rat cortical neurons in vitro and showing that: the silk-based biomaterial fulfils all key biomaterial properties required for spinal repair, DHA promotes excellent neuronal outgrowth and DC EF aids guidance of neuronal growth cones. In further experiments, it was demonstrated that DHA and DC EF, alone and in combination, can overcome the inhibitory effects on axonal growth caused by chondroitin sulphate 6, a molecule highly upregulated after SCI. In conclusion, the strategies investigated here meet the major biochemical criteria for spinal repair in vitro and their potential in combination may be verified in in vivo SCI models.
Supervisor: Huang, Wenlong. Sponsor: Institute of Medical Sciences
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Spinal cord ; Biomedical materials