Graduation Year
2020
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Biomedical Engineering
Major Professor
Piyush Koria, Ph.D.
Committee Member
William Lee, Ph.D.
Committee Member
Nathan Gallant, Ph.D.
Committee Member
Mark Jaroszeski, Ph.D.
Committee Member
Joseph Walton, Ph.D.
Keywords
Drug-Delivery, Elastin-Like-Peptide, Engineering, Nanomedicine, Protein
Abstract
Chronic wounds are those wounds which are refractory to treatment, often taking years to heal. These wounds are complex and may present with elevated protease levels, resulting in rapid degradation of growth factors, both native and augmented via treatment. This study’s focus was the development of a system to protect growth factors from protease mediated degradation.
The protective system consisted of chimeric fusion proteins developed to contain both a growth factor or known protease inhibitory peptide and an Elastin-Like-Peptide (ELP)component. The unique phase transitioning abilities of the ELP component allowed for the self-assembly of these chimeric fusion proteins into a heterogenous nanoparticle which puts the inhibitory component near the growth factor.
These developed heterogenous nanoparticles showed success in protecting and preserving the growth factor in highly proteolytic environments as well as in human chronic wound fluid. Treatment with these nanoparticles in a protease augmented diabetic mouse model were found to result in enhanced collagen remodeling and resolution of inflammation.
This system is novel as it places the protease inhibitor in close proximity to the growth factor, allowing for inhibition of proteases in the immediate environment surrounding the growth factor. In addition, this system is highly modular, allowing for the protection of multiple growth factors using the same inhibitor, without having to alter the amino acid sequences of each individual growth factor.
Our results suggest that the developed protective system holds tremendous promise and potential in the field of wound healing therapy and may help bridge the translation of growth factor therapies to the clinic. In addition, the modular nature of this nanoparticular system allows for the opportunity to customize protective systems across several fields in research and medicine.
Scholar Commons Citation
Boeringer, Tabitha, "Protease Resistant Growth Factor Formulations for the Healing of Chronic Wounds" (2020). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/9527