Team:Lubbock TTU/Description

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Project Overview

In 2010 it was estimated that 6.5 million people in the United States alone suffered from chronic wounds, accruing an annual cost of approximately $2.5 billion. Furthermore, experts predict that the burden of chronic wounds will increase rapidly in the near future due to increasing medical costs, an aging population, and the emergence of antibiotic resistant bacteria. Chronic wounds are characterized by their inability to progress through an orderly set of stages within a time period of about three months. Wound healing progresses through four successive stages known as hemostasis, inflammation, proliferation and remodeling.

        

The etiology of chronic wounds is very diverse, but patients frequently suffer from persisting chronic wounds arrested in the inflammation phase due to overproduction of wound site proteases. In turn, proteases inhibit the proliferation phase by degrading growth factors meant to induce tissue growth. They also inhibit tissue remodeling by degrading the collagen scaffold, which new cells migrate into. Thus, proteases decrease wound healing rates by degrading host growth factors and the extracellular matrix of the wound site.

Our team is using a bioreactor and synthetic biology principles to purify and infuse a synthetic collagen scaffold with platelet derived growth factor (PDGF) and Aprotinin to induce the healing process of chronic wounds. Synthetic collagen scaffolds are currently being used as a replacement for skin grafts in the treatment of burn victims. They have been shown to increase wound healing by attracting tissue cells, such as keratinocytes and aiding in angiogenesis and re-epithelialization.

In our collagen scaffold, the aprotinin serves to prevent degradation from wound site proteases. Furthermore, recent studies have shown that aprotinin can increase angiogenesis, ultimately improving synthetic scaffold integration efficiency. PDGF has been well studied in the past and is the first growth factor to be approved by the FDA for human treatment. Currently ointments infused with PDGF, such as REGRANEX are being used to treat chronic wounds. We envision that our technology will help to introduce a novel synthetic-biology-based process for the development of therapeutic wound dressings. Learn more.

 

Our Goals

We will use synthetic biology principles to help treat chronic wounds by targeting the overproduction of wound site protease.

• For Aim 1 we will genetically engineer E. coli to produce a protease inhibitor and platelet derived growth factor.
• For Aim 2 we will purify the protease inhibitor and platelet derived growth factor in a bioreactor.
• For Aim 3 we will design a collagen bandage that mimics the human extracellular matrix, and infuse it with purified protease inhibitor and platelet derived growth factor.

Our approach is two-fold. By infusing the collagen extracellular matrix with platelet derived growth factor and protease inhibitor, chronic wounds should be able to progress past the inflammation phase and begin healing once again.

What We Accomplished →

Aim 1

We were able to design constructs for two therapeutic proteins, aprotinin and platelet derived growth factor (PDGF). Our goal was to use these therapeutic proteins to decrease wound healing times. Aprotinin, being a matrix-metalloprotease (MMP) inhibitor, will inhibit wound-site proteases, preventing these proteases from breaking down the healing extra-cellular matrix (ECM). PDGF will stimulate cellular regeneration in chronic wounds, helping to speed up and fortify the wound healing process.

 

Experimental Data →