A Bottom-up Proteomic Approach to Address Protease Activity in Biomimetic Polymer Membranes

The importance of scar management has never been as significant as today. People have become more self -conscious of their scars, given the increasing media focus on aesthetics. Thus, scar prevention/treatment is more likely than ever before. The worst result from scars, is the development of keloid scars, which are painful, disfiguring, and are aesthetically unpleasant. Keloids proximal to bone joints can even limit the mobility of patients. More annoyingly, they frequently persist at the site of injury, recurring after treatment. Although much has been learnt about their pathophysiology, existing treatments including corticosteroid injection, pressure dressing, and surgery have limited efficacy, are neither readily accessible nor patient-friendly. Recently, Xu’s laboratory at NTU observed that the proliferation of keloid fibroblasts could be prohibited in the presence of drug-free microneedles. All fibroblasts in the petridish (both touched and untouched by microneedles) lost their spindle shaped morphology, recessed into a high nuclear:cytoplasm appearance, and reduced their proliferation activity. Animal studies with the rabbit hypertrophic scar model also concurred, with less hypertrophic scar formation when higher microneedle densities were used. More impressively, in a feasibility study on a keloid patient, the drug-free microneedle patch was able to penetrate into keloid and prevented the continuous growth of keloid while the uncovered part of the same keloid continued to grow. Based on these observations, the team plan to understand the underlying cellular/molecular mechanism of this unique phenomenon through utilizing micropatterning technology, developed in Mrksich’s laboratory (NU). Specifically, we will develop a group of micropatterned substrates that control the cell -cell communication. Then we will examine the influence of microneedle-treatment over the cell viability, expression of collagen, connective tissue growth factor, TGF- β