Bioscaffold engineering for cardiac progenitor transplantation

Abstract

Cell retention is the major bottleneck impeding the efficacy of cell therapy approaches in the regenerative medicine field. There is significant interest in monitoring the engraftment of transplanted cells and developing in vivo-detectable scaffolds to efficiently deliver and retain the cells within the transplant site. This thesis chronicles the design and development of a multi-modal in vivo-detectable hydrogel platform system with tailorable degradation properties to transport and monitor the engraftment of Luciferase-2 transduced clonally derived adult mouse platelet derived growth factor receptor α positive cardiac progenitor cells (CPC-Luc2) in vivo. The optimal structure of the hydrogel system was determined through the examination of the degradation properties, mechanical properties and cellular interactions with the considered materials. The optimised hydrogel scaffold design is comprised of poly(ethylene glycol) (PEG) crosslinked with heparin-binding peptides (HBP) that have been functionalised with Gadolinium (III) in order to monitor the localisation and degradation of the hydrogel system in vivo through MRI detection strategies. The HBP are able to bind growth factor-binding glycosaminoglycans within the ECM. Inclusion of these moieties in our hydrogel design maintains the metabolic activity of encapsulated cells through 14 days in vitro. The material is tailored towards cardiac applications implementing a gel formulation capable of displaying mechanical properties resembling those of cardiac tissue and encapsulating CPC-Luc2. Improvement in progenitor retention in the myocardium and mouse hind limbs are seen at 3 days for CPC- Luc2 encapsulated in the HBP hydrogels. This optimised system presents a novel multifunctional scaffold system that can be monitored in vivo through various imaging strategies. This is a model system towards understanding and mapping the in vivo behaviour of transplanted cells and biomaterials while providing a platform for recruitment of additional supplemental factors to enhance and measure cell viability, proliferation, and engraftment.