A Chemical Synthesis Paradigm for in utero Repair of Spina Bifida

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Spina Bifida - literally meaning “split spine” in Latin - is the most common birth defect with 0.2 % occurrence worldwide. It is due to foetus’ spine failing to close during the first month of pregnancy, resulting in the exposure of nerves to the amniotic fluid, with permanent consequences affecting both cognitive and psychometric capacities. To date no treatment exists and the damage to the nerves is irreversible. However, a possible solution could lie in the so-called “double hit hypothesis”, which conjectures that covering the opening in the spinal cord either with a material non-permeable to the amniotic-fluid would protect the nerves or with a matrix for the tissue to grow on would prevent the induced life-long complications.
This project aims to design, synthesize, and characterise biocompatible hydrogels from functionalised polymers and crosslinked microgels which would adhere to the spina bifida opening to form either a tough and highly flexible protective wound dressing that seals the nerves from the amniotic fluid or provide a scaffold for cells to spread on. Hydrogels appear as a material of choice in tissue engineering because of their elasticity and tensile strength very close to human tissues. Recent research in wound healing has highlighted the potential of polysaccharides as adhesive, biocompatible materials.
To this end, chitosan was derivatised with carbic anhydride to provide a range of functionalised polymersthat could be crosslinked via thiol-ene photoclick chemistry. The mechanical properties of the resulting hydrogels could be varied by controlled and preliminary cell studied highlighted their potential applications in tissue engineering. Alternatively, microgels could be successfully prepared by using water-in-oil nano-emulsions as templates, with gelation facilitated by in situ photo-initiated cross-linking. Both materials presented limited cytotoxicity and demonstrated promising initial properties for in utero management of Spina Bifida. In the course of this study, unexpected gelation condition of chitosan was also observed which were not precedented in literature. A new gelation mechanism was proposed which could be of interest to the scientific community.
Date of Award24 Mar 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorM C Galan (Supervisor), Wuge H Briscoe (Supervisor) & Terence Cosgrove (Supervisor)

Cite this

A Chemical Synthesis Paradigm for in utero Repair of Spina Bifida
Michel, S. E. S. (Author). 24 Mar 2020

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)