Design of Bioactive Composite Tissue Engineering

Design of Bioactive Composite Tissue Engineering

Student(s):

Reynaldo Flores

Elizabeth R. Kreienkamp

Jessica A. Sanneman

Advisor(s):

Dr. Gary Bledsoe

Dr. Kyle Mitchell

For the most up-to-date information, visit the students project website.

Project Abstract

Successful healing of long-term dermal wounds (such as diabetic ulcers) in patients has been a continuous problem for doctors for decades. Recent research has shown that bioactive glass is promising in inducing wound healing. Consequently, its use in tissue engineering scaffolds for the regrowth of soft tissues is increasing.

The goal of this work is to explore its possible use in other applications. It is hoped that the method of constructing biodegradable polymer-bioactive glass composite scaffolds with angiogenic properties can be investigated and an optimal scaffold be designed. By adding bioactive glass to ongoing dermal wounds, a low-oxygen environment is mimicked, initiating the process of wound healing that would otherwise not occur.

In the design of the bioactive composite scaffold, the specific composition will depend largely on material costs and biocompatibility. However, design goals are to create long-lasting composite scaffolds composed of a monomer such as Polycaprolactone (PCL), a photoinitiator, bioactive glass, and human fibroblast cells. For this project, a cobalt-doped bioactive glass can be introduced to the scaffold and compared to the scaffold with undoped bioactive glass. Research has shown that cobalt, being similar in size to iron, will interfere with the iron bound to the oxygen in the HIF-α pathway and effectively inactivate the prolyl hydroxylase enzyme. The interference of this enzymatic pathway tricks cells into believing that they are in a hypoxic environment, which keeps the HIF-α pathway turned on, and causes cells to produce vascular endothelial growth factor (VEGF) that then provokes the formation of new blood vessels.

By utilizing the degradation rate of a polymer to control the rate of bioconversion of the bioactive glass, it is possible to control the amount of ions released into the wound that mimic the hypoxic response to facilitate the initiation of angiogenesis. In all, the insertion of a composite scaffold into an ongoing dermal wound could allow for the control of the best response for optimal wound healing of the patients’ injury.

Experimentation can be done with different ratios of the degradable polymer to other components to see if polymer-bioactive glass composites will form via photopolymerization. Once a successful composition of the composite scaffolds have been fabricated, scaffolds with different shapes/sizes, compositions, degradation rates, and types of bioactive glass can be designed for enhancing wound healing.

To accurately determine the scaffolds’ ability to induce wound healing, cell viability within the scaffolds can be studied using assays and thorough analysis of the scaffold via microscopy. If time permits and additional funding can be found, VEGF ELISA kits can be used to determine the amount of VEGF produced by the fibroblasts to indirectly show how the scaffold would affect a wound’s progress.