Micro-patterned polymer substrates as novel models of epidermal wound healing

The proposed research will develop a novel in vitro model of wound healing within the skin. We will employ state-of-the-art micro-fabrication techniques to create engineered substrates for culturing human keratinocytes. This technology will allow us to precisely control multiple parameters of the wound environment. Specifically, we will determine how the composition, geometry, and stiffness of the wound influence cell behaviour. In addition, we will examine the molecular signalling pathways that regulate the cellular responses to these different environments. This project has the potential to provide significant insights into how human skin cells sense and respond to extrinsic signals during the wound healing process. Moreover, this model system may be a powerful tool for future cell biology studies, drug screening, and other types of translational research.

The overall objective of the proposed research is to determine how human keratinocytes sense and respond to changes in their environment during wound healing. Micro-contact printing techniques will be used to create a novel in vitro model of epidermal wound healing. Micro-patterned substrates will consist of islands of protein resistant polymer brushes, which will serve as model 'wound beds', and will be surrounded by confluent human keratinocytes. Migration into the wound will be activated by coupling specific extracellular matrix proteins to the polymer brushes. This system will allow us to precisely control the size, shape, and composition of the wound bed. In addition, this assay will be used to investigate the role of serum response factor (SRF) signalling in keratinocyte mechano-sensing during the wound healing process. This work will be carried out in three specific aims and test two major hypotheses: (1) The composition and structure of the wound bed regulates re-epithelialization via altered migration and proliferation of the keratinocytes. (2) SRF mediates cellular responses to physical cues during epidermal wound healing.

The main objective of the project is to improve our fundamental understanding of the normal wound healing process through the use of a novel in vitro system. While the immediate benefits of this knowledge will be to related academic communities, the model system may have long-term benefits to the UK economy and to public health and well-being. Our model of wound healing may be a useful assay for screening new compounds or bio-active molecules for treating chronic ulcers or skin diseases. As a tool for pharmaceutical companies, this model could benefit the UK and world economy. More importantly, the assay could aid the drug development process and lead to improved treatments for patients and overall public health. The knowledge generated by the proposed studies may also provide important information for wound management and tissue repair. Our studies will establish the basic role of physical cues in the normal wound healing process. This information may be useful to those in the tissue engineering field and provide design criteria for biomaterials and tissue scaffolds. Understanding the physical regulation of wound healing may also be important for healthcare professionals when applying wound dressings and sutures. Therefore, this project could benefit the economy by guiding the development of new tissue engineering and regenerative medicine products. Patients would also benefit from more effective products and treatments. Beyond the pharmaceutical and healthcare industries, this project may stimulate the materials and chemical industries. By providing a new application for micro-contact printing and polymer brushes, this project may lead to the development of new materials, chemicals, or processes that are more ideally suited for these types of experimental systems.