Graduation Year

2022

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

Nathan Gallant, Ph.D.

Committee Member

Mark Jaroszeski, Ph.D.

Committee Member

William Lee, Ph.D.

Committee Member

Martin Muschol, Ph.D.

Keywords

Chronic Wound, Inverse Phase Transitioning, Mesenchymal Stem Cells, Protease Inhibitor, Recombinant Technology

Abstract

Chronic wounds present many clinical challenges in relation to the successful treatment and closure of the damaged tissue. Most current treatment methods focused on one or two aspects to drive wound closure, while most chronic wounds are multifactorial environments with many of those dependencies relying on the termination of one another to effectively gain tissue construction, closure, and full skin thickness and composition. Natural wound healing processes allude to potential biologics that can impede the chronic breakdown of tissue, while restoring deposition of new tissue, and effectively leading to a healed wound. Proteases secreted by the body’s immune system lay waste to even the healthy tissues in wounds, which can be seen in those that turn chronic, as a progressive and persistent break down of tissue, proteins, and cells in the wound site. The disruption of this exacerbated tissue breakdown is both essential to quell the destruction of healthy tissues as well as other proteins such as growth factors that are needed to signal for the development and deposition of new tissue. The latter points to the importance of the balance between tissue break down and deposition, commonly referred to as remodeling, as a focusing point for the healing of chronic wounds. The two generalized secreted molecules that balance tissue breakdown and deposition are proteases and growth factors respectively. However, the efficacy of growth factors that exist in a wound site are highly dependent upon the concentration of secreted proteases. Therefore, in chronic wounds the proteases which are continuously secreted, without intrinsic inhibition, will chew up the growth factors responsible for signaling deposition, which causes tissue destruction to be the overpowering and vicious result. The protein-based combination therapy created here works to rebalance tissue breakdown and deposition to tend toward minimal deconstruction with overpowering construction. It works by inhibiting proteases, flooding the site with many growth factors, while also sustaining the presence of the treatment over longer periods to avoid site disturbance and leakage of the biologic combination into neighboring tissues. This protein combination is a powder-based freeze dried therapeutic, that can be used in powder form or reconstituted into many mediums and materials for desired application and results. It is a multifunctional treatment, with the main controlling factor for application being wound size as a governing guideline for dosage, as it can be applied in many different forms such as raw powder, liquid, gel, and in materials for an application tailored to the characteristics of the treatment site.

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