Resilin-like polypeptide-poly(ethylene gylcol) hybrid hydrogels for mechanically-demanding tissue engineering applications
| Author(s) | McGann, Christopher Leland | |
| Date Accessioned | 2015-10-16T14:05:57Z | |
| Date Available | 2015-10-16T14:05:57Z | |
| Publication Date | 2015 | |
| Abstract | Technological progress in the life sciences and engineering has combined with important insights in the fields of biology and material science to make possible the development of biological substitutes which aim to restore function to damaged tissue. Numerous biomimetic hydrogels have been developed with the purpose of harnessing the regenerative capacity of cells and tissue through the rational deployment of biological signals. Aided by recombinant DNA technology and protein engineering methods, a new class of hydrogel precursor, the biosynthetic protein polymer, has demonstrated great promise towards the development of highly functional tissue engineering materials. In particular, protein polymers based upon resilin, a natural protein elastomer, have demonstrated outstanding mechanical properties that would have great value in soft tissue applications. This dissertation introduces hybrid hydrogels composed of recombinant resilin-like polypeptides (RLPs) cross-linked with multi-arm PEG macromers. Two different chemical strategies were employed to form RLP-PEG hydrogels: one utilized a Michael-type addition reaction between the thiols of cysteine residues present within the RLP and vinyl sulfone moieties functionalized on a multi-arm PEG macromer; the second system cross-links a norbornene-functionalized RLP with a thiol-functionalized multi-arm PEG macromer via a photoinitiated thiol-ene step polymerization. Oscillatory rheology and tensile testing confirmed the formation of elastic, resilient hydrogels in the RLP-PEG system cross-linked via Michael-type addition. These hydrogels supported the encapsulation and culture of both human aortic adventitial fibroblasts and human mesenchymal stem cells. Additionally, these RLP-PEG hydrogels exhibited phase separation behavior during cross-linking that led to the formation of a heterogeneous microstructure. Degradation could be triggered through incubation with matrix metalloproteinase. Photocross-linking was conferred to RLPs through the successful conjugation of norbornene acid to the protein. Oscillatory rheology characterized the gelation and subsequent mechanical properties of the photoreactive RLP-PEG hydrogels while the cytocompatibility was confirmed via the successful encapsulation and culture of human mesenchymal stem cells. Both strategies demonstrate the utility of hybrid materials that combine biosynthetic proteins with synthetic polymers. As resilient and cytocompatible materials, RLP-PEG hybrid hydrogels offer an exciting strategy towards the development of biomimetic tissue engineering scaffolds for mechanically-demanding applications. | en_US |
| Advisor | Kiick, Kristi L. | |
| Degree | Ph.D. | |
| Department | University of Delaware, Department of Materials Science and Engineering | |
| Unique Identifier | 925369333 | |
| URL | http://udspace.udel.edu/handle/19716/17169 | |
| Publisher | University of Delaware | en_US |
| URI | http://search.proquest.com/docview/1708646896?accountid=10457 | |
| dc.subject.lcsh | Colloids. | |
| dc.subject.lcsh | Polyethylene glycol. | |
| dc.subject.lcsh | Resilin. | |
| dc.subject.lcsh | Tissue engineering. | |
| dc.subject.lcsh | Fibroblasts. | |
| dc.subject.lcsh | Mesenchymal stem cells. | |
| Title | Resilin-like polypeptide-poly(ethylene gylcol) hybrid hydrogels for mechanically-demanding tissue engineering applications | en_US |
| Type | Thesis | en_US |