A Chemical Synthesis Paradigm for In Utero Repair of Spina Bifida

PS2 Poster session 2 Even numbers
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15

Sarah Michel1, Mark Dembow2, Carmen Galan1, Wuge Briscoe1

1School of Chemistry, University of Bristol, Bristol, United Kingdom, 2Fetal Medicine Unit, St Michael's Hospital, Bristol, United Kingdom

Spina Bifida - literally meaning “split spine” in Latin - is the most common birth defect with 0.2 % occurrence worldwide [1]. 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 [2]. 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 with a material non-permeable to then amniotic-fluid would protect the nerves and therefore prevent the induced life-long complications [3]. 

This project aims to design, synthesize, and characterise biocompatible hydrogels and microgels which would adhere to the spina bifida opening to form tough and highly flexible protective wound dressing that seals the nerves from the amniotic fluid. Hydrogels appear as a material of choice in tissue engineering because of their elasticity and tensile strength very close to human tissues [4, 5]. Recent research in wound healing has highlighted the potential of polysaccharides as adhesive, biocompatible materials [6]. 

To this end, chitosan was derivatised with carbic anhydride to provide a range of functionalised polymers that 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 with a diameter varying between 150 and 300 nm could be successfully prepared by using water-in-oil nanoemulsions as templates, with gelation facilitated by in situ photo-initiated cross-linking. The microgel particles were then isolated and characterised by dynamic light scattering (DLS), Zeta potential measurements and electron microscopy. The outer shell of the microgels was successfully functionalised by click chemistry to allow further generation of complex wound healing materials [7].  

Figure 1. Synthesis of chitosan-functionalised microgels.

  1. Parker, SE et al. Birth Defects Res A Clin Mol Teratol. 2010, 88, 1008.
  2. Adzick, NS. Seminars in Fetal & Neonatal Medicine, 2010, 15, 9.
  3. Watanabe, M et al. Fetal Diagn Ther 2015, 37, 197.
  4. Geckil, H et al. Nanomedicine (Lond). 2010, 5, 469.
  5. Briscoe, W.H. et al Materials 2016, 9, 443.
  6. Agrawal, P et al. The International Journal of Lower Extremity Wounds 2014, 13, 180.
  7. Michel, SES et al. ACS Applied Bio Materials. Submitted.