In-situ Formed Bioactive Stem Cell Hydrogel Dressings from PEG-based Multifunctional Copolymers for Wound Healing

Abstract

Wound healing, especially chronic wound healing, has become a major clinical problem all over the world. Among all the treatments for wound healing, wound dressings are the main management approaches for both acute and chronic wounds. However, although significant progress has been made in the development of modern wound dressings over the past few years, there are still restrictions to stimulating the healing process. As an alternative to existing approaches, tissue engineering approaches with stem cell therapy have been widely studied for wound healing applications and showed promising therapeutic effects. Ideally, the next step is to develop a wound dressing with specific therapeutic functions such as delivering therapeutic agents (e.g. growth factors and/or stem cells) to promote the healing process. The overall goal of this doctoral project was to develop an injectable hydrogel cell delivery system which could easily encapsulate and support adipose-derived stem cells\u27 (ADSCs) growth, proliferation and secretion, with the potential use as a temporary bioactive hydrogel dressing for wound healing applications. To this end, the multifunctional PEG-based hyperbranched copolymers with thermoresponsive behavior and in-situ photo-/chemical cross-linkable properties have been developed via an advanced one-step in-situ deactivation enhanced atom transfer radical polymerization (DE-ATRP) method. At room temperature, this copolymer was water-soluble while forming a gel rapidly at body temperature, so that the cells can be easily encapsulated and applied to any wound size, shape or cavity, which is less invasive than other approaches and minimizes patients\u27 discomfort. In addition, a photo-/chemical gelation occurs within a short time to achieve a stable hydrogel with enhanced mechanical properties, supporting cell growth, proliferation and secretion. Furthermore, in combination with extracellular matrix (ECM) biopolymer of hyaluronic acid (HA), the microenvironment of the hydrogel system has been optimized during the project, so that the encapsulated ADSCs can maintain their viability and secretion level in vitro. Finally, the in vivo cell survival, material inflammatory response, and the wound healing effect of the optimized hydrogel system with rat ADSCs were evaluated using a rat dorsal excisional wound model. It was found that this system prevented the wound contraction and significantly enhanced angiogenesis. This is the first study to describe an injectable stem cell bioactive hydrogel dressing for wound healing purpose; and with the advanced multifunctional polymer and injectable hydrogel template developed in this project, there is significant potential for further development of this technique to the next step towards the realization of clinical wound healing applications ultimately.2017-07-3