Advanced cell therapies require robust delivery materials, and silk is a promising contender. This biopolymer already has a long clinical track record and can be assembled into a range of material formats, including hydrogels (Chapter 1). The hypothesis of this thesis was that reverse engineered silk could be programmed to form a self-assembling silk hydrogel for stem cell delivery.Therefore, the aim of this thesis was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix for stroke treatment. Sonication energy was used to programme the transition of the silk (1 to 5% w/v) secondary structure from a random coil to a stable β-sheet configuration (Chapter 3). This allowed the fine tuning of self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling (Chapter 3) and to support uniform cell distribution as well as cell viability (Chapter 4).Embedded cells underwent significant proliferation over 14 days, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs showed significantly better viability after injection through a 30G needle when the gels were in the pre-gelled state versus post-gelled state (Chapter 4). Silk hydrogels with physical characteristics that matched those of brain tissue showed good space conformity after stereotaxic injection into an ischaemic stroke lesion in mice (Chapter 5).Overall, this thesis demonstrates that silk hydrogel is a promising cell delivery (MSC) platform for central nervous system diseases, especially stroke.
|Date of Award||1 Apr 2017|
- University Of Strathclyde
|Supervisor||Hilary Carswell (Supervisor) & Philipp Seib (Supervisor)|