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

Project: Research project

Project Details

Description

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 pathway signalling and inflammatory biomarkers etc. The ultimate goal is to uncover the therapeutic mechanism of drug-free microneedles in keloid treatment, which can allow us to design more efficient/effective therapeutics or methodology.
StatusFinished
Effective start/end date11/1/1410/31/19

Funding

  • Nanyang Technological University (Agmt 10/20/2014)

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