BME PhD Proposal Seminar: Amy H. Van Hove
Development of Hydrogels for the Controlled Delivery of Pro-Angiogenic Peptides and Mesenchymal Stem Cells
8 million Americans are afflicted with peripheral arterial disease, and an estimated 17.6 million suffer from coronary heart disease, responsible for ~1 in every 6 deaths in the United States. Treatment options for these diseases are limited, and no FDA approved pro-angiogenic treatments exist to robustly enhance vascularization within these ischemic tissues. Some success has been achieved inducing therapeutic angiogenesis through the use of large angiogenic proteins or treatment with mesenchymal stem cells. However, these methods are limited as simple injection of proteins or cells into ischemic tissue results in rapid clearance of the therapeutic agent, motivating the development of a biomaterial to enhance localization and therapeutic efficacy. This work presents the development of poly(ethylene glycol) (PEG) hydrogels incorporating pro-angiogenic, cell-releasable peptides for the encapsulation of mesenchymal stem cells, creating a stimuli-responsive therapeutic biomaterial aimed at increasing host tissue angiogenesis.
Nine angiogenic peptides identified from literature were synthesized and their relative efficacy compared via the
human umbilical vein endothelial cell proliferation and tube formation assays. As the enzymatically-responsive peptide
tether linking pro-angiogenic peptides into the PEG hydrogel leaves residual amino acid
tails on the peptides
upon their release from the hydrogel, peptides were tested as the pro-angiogenic sequence alone and with the
pro-angiogenic sequence flanked by these
tails. Testing identified three peptides that retained their bioactivity
tails present: Qk, SPARC113, and SPARC118. SPARC118 was then incorporated
into PEG hydrogels via the enzymatically-responsive peptide tethers, and enzymatically-responsive hydrogel degradation and
peptide release was demonstrated.