1409 High-throughput drug screening system targeting tissue fibrosis: An application of PDMS stretch platform

Abstract

Fibrosis is a process of abnormal accumulation of extracellular matrix (ECM) substrates, which have been a key driver of progressive organ dysfunction. Keloids are representative fibro-proliferative disease of skin with abnormal fibroblast activity. However, the treatment options are limited and current drug development platforms cannot fully reflect mechanosensitive property of the disease. Strain devices with an expandable silicone such as polydimethylsiloxane (PDMS) culture membranes can mimic mechanically dynamic tissue environments. Here, we established a PDMS based stretchable culture system to evaluate as a drug screening platform. Patient-derived keloid fibroblasts were cultured on the PDMS stretch platform. In response to cyclic stretch, the cellular proliferation reached the optimal activity level. Afterwards, the cells were treated with corticosteroids as a positive control and drugs with anti-fibrosis activity were selected. Expression of fibrosis-related proteins was evaluated; TGF-β was significantly reduced and type 1 collagen was subsequently reduced too (p < 0.05). It is notable that the PDMS platform were sufficient to demonstrate a drug response as in physiologic conditions owing to its own mechanical property of cyclic stretch. For future treatment approaches, our model may facilitate high-throughput screening under a physiologic condition.