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Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels
Objectives: Vascular diseases are one of the leading causes of death. Due to minimal regenerative capability of the heart, alternative therapies have been sought after with engineered biomaterials being extensively investigated in this area. In this study, enzymatically degradable heparinised polyet...
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| Format: | Thesis |
| Language: | English |
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Department of Human Biology
2017
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| _version_ | 1867613342362763265 |
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| access_status_str | Open Access |
| author | Chokoza, Cindy |
| author2 | Davies, Neil |
| author_browse | Chokoza, Cindy Davies, Neil |
| author_facet | Davies, Neil Chokoza, Cindy |
| author_sort | Chokoza, Cindy |
| collection | Thesis |
| description | Objectives: Vascular diseases are one of the leading causes of death. Due to minimal regenerative capability of the heart, alternative therapies have been sought after with engineered biomaterials being extensively investigated in this area. In this study, enzymatically degradable heparinised polyethylene glycol (PEG-Hep) hydrogels were synthesized and characterised for the binding and controlled release of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), as well as their bioactivity and angiogenic potential in vivo. Methodology: VEGF and bFGF were combined into 4% (m/v) PEG-Hep hydrogels. The binding and release rates of VEGF and BFGF were analysed via an immunosorbent assay. Released growth factor bioactivity was measured using an XTT metabolic assay on human saphenous vein endothelial cells and human dermal fibroblasts. Neovascularisation was quantified in a subcutaneous rat angiogenesis model in which hydrogel growth factor combinations were implanted within porous polyurethane discs and analysed after a 4 week period. A novel hybrid hydrogel able to degrade proteolytically and hydrolytically was further developed, characterised and analysed as above. Results: PEG-Hep hydrogels demonstrated substantial growth factor binding ability (500-600 ng) and allowed sustained release (10-20 ng/day) for up to 28 days. Bioactivity of the growth factors was retained throughout the release period. The degradation rate of the hydrogels could be controlled in vivo by varying the ratio of monomers capable of forming either hydrolytically or proteolytically degradable crosslinks. Qualitative and quantitative analysis demonstrated a pronounced and significant angiogenic response in vivo (p<0.05). Conclusion: Heparinised PEG hydrogels show significant promise as controlled release vehicles for growth factors and warrant further examination in a myocardial infarction model. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/24891 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:34:36.552Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | Department of Human Biology |
| publisherStr | Department of Human Biology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/24891 Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels Chokoza, Cindy Davies, Neil Bezuidenhout, Deon Biomaterials Objectives: Vascular diseases are one of the leading causes of death. Due to minimal regenerative capability of the heart, alternative therapies have been sought after with engineered biomaterials being extensively investigated in this area. In this study, enzymatically degradable heparinised polyethylene glycol (PEG-Hep) hydrogels were synthesized and characterised for the binding and controlled release of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), as well as their bioactivity and angiogenic potential in vivo. Methodology: VEGF and bFGF were combined into 4% (m/v) PEG-Hep hydrogels. The binding and release rates of VEGF and BFGF were analysed via an immunosorbent assay. Released growth factor bioactivity was measured using an XTT metabolic assay on human saphenous vein endothelial cells and human dermal fibroblasts. Neovascularisation was quantified in a subcutaneous rat angiogenesis model in which hydrogel growth factor combinations were implanted within porous polyurethane discs and analysed after a 4 week period. A novel hybrid hydrogel able to degrade proteolytically and hydrolytically was further developed, characterised and analysed as above. Results: PEG-Hep hydrogels demonstrated substantial growth factor binding ability (500-600 ng) and allowed sustained release (10-20 ng/day) for up to 28 days. Bioactivity of the growth factors was retained throughout the release period. The degradation rate of the hydrogels could be controlled in vivo by varying the ratio of monomers capable of forming either hydrolytically or proteolytically degradable crosslinks. Qualitative and quantitative analysis demonstrated a pronounced and significant angiogenic response in vivo (p<0.05). Conclusion: Heparinised PEG hydrogels show significant promise as controlled release vehicles for growth factors and warrant further examination in a myocardial infarction model. 2017-08-17T14:15:34Z 2017-08-17T14:15:34Z 2017 Master Thesis Masters MSc (Med) http://hdl.handle.net/11427/24891 eng application/pdf Department of Human Biology Faculty of Health Sciences University of Cape Town |
| spellingShingle | Biomaterials Chokoza, Cindy Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| thesis_degree_str | Master's |
| title | Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| title_full | Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| title_fullStr | Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| title_full_unstemmed | Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| title_short | Stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| title_sort | stimulation of angiogenesis through growth factor delivery from synthetic heparinised hydrogels |
| topic | Biomaterials |
| url | http://hdl.handle.net/11427/24891 |
| work_keys_str_mv | AT chokozacindy stimulationofangiogenesisthroughgrowthfactordeliveryfromsyntheticheparinisedhydrogels |