Text

theses

ETD graduate

Chronic wounds are characterized as non-healing wounds due to poor angiogenesis, impaired vascularization, collagen formation, and dysfunctional fibroblasts and keratinocytes in the hypoxic wound environment. Recent studies have demonstrated the use of growth factors for enhanced wound healing due to their ability to promote proliferation and migration of cells, stimulate collagen synthesis and augment angiogenesis. Platelet-derived growth factor (PDGF) is one of the earliest growth factors to be identified and clinically used for the treatment of chronic wounds. However, their applications are limited because of the increased level of proteases in the hostile wound environment which degrades the growth factors, thus impeding their activity. Here, we have developed and characterized a recombinant fusion protein comprising PDGF and elastin-like polypeptide (ELP). The phase transitioning property of ELP allows rapid purification of the fusion protein using inverse temperature cycling (ITC). The fusion protein retained all characteristics of PDGF-A as evident from fibroblast and endothelial cell proliferation and migration, and endothelial formation of a tube network similar to native PDGF. The self-assembling property of ELP caused the formation of nanoparticles at physiological temperature, which acted as an optimal and stable delivery mechanism for the wound environment. We used 5 nM concentration of PDGF-ELP to show an increase in proliferation by ~2 fold, ~90% wound closure after 48 hours using cell-based scratch assays, and increased angiogenesis demonstrated by enhanced capillary-like tube network formation using a tube assay.

ETD_10995

M.S.

Includes bibliographical references

doi:10.7282/t3-49sd-gk36

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