Abdo Dhana, Zhao Yimu, Okhovatian Sargol, Jiménez Vargas Luis Felipe, Wagner Karl T, Shakeri Amid, Vosoughi Daniel, Radisic Milica
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 27 King's College Circle, Toronto, ON, M5S 1A1, Canada.
Acceleration Consortium, University of Toronto, Toronto, ON, M5S 1A1, Canada.
Mater Today Bio. 2025 Jul 18;34:102111. doi: 10.1016/j.mtbio.2025.102111. eCollection 2025 Oct.
Dermal fibrosis is a significant barrier to effective wound healing, with excessive myofibroblast activation and extracellular matrix deposition leading to scar formation and compromised tissue function. Current models for studying dermal fibrosis, such as monolayer cultures and human skin equivalents (HSEs), have limited physiological relevance or scalability for drug screening. Here, we present a dermis-on-a-chip platform to enable screening of anti-fibrotic compounds in physiologically-relevant 3D dermal microtissues. Upon treatment with transforming growth factor beta (TGFβ), the tissues exhibited hallmarks of fibrosis, including impaired integrity, increased tensile forces, altered cellular morphology, and a pro-fibrotic cytokine profile. Conversely, incorporation of QHREDGS (Q-peptide), an angiopoietin-1 derived peptide with known regenerative properties, selectively modulated these fibrotic changes. Q-peptide was found to reduce TGFβ-induced tensile forces, suppress smooth muscle actin (SMA) expression, and upregulate certain cytokines associated with wound repair. Overall, these findings demonstrate the utility of our dermis-on-a-chip model in compound screening.
皮肤纤维化是有效伤口愈合的重大障碍，成肌纤维细胞过度活化和细胞外基质沉积会导致瘢痕形成并损害组织功能。目前用于研究皮肤纤维化的模型，如单层培养和人皮肤等效物（HSE），在药物筛选方面生理相关性有限或可扩展性不足。在此，我们展示了一种芯片上真皮平台，用于在生理相关的三维真皮微组织中筛选抗纤维化化合物。用转化生长因子β（TGFβ）处理后，组织呈现出纤维化特征，包括完整性受损、张力增加、细胞形态改变以及促纤维化细胞因子谱。相反，掺入QHREDGS（Q肽），一种具有已知再生特性的血管生成素-1衍生肽，可选择性调节这些纤维化变化。发现Q肽可降低TGFβ诱导的张力，抑制平滑肌肌动蛋白（SMA）表达，并上调与伤口修复相关的某些细胞因子。总体而言，这些发现证明了我们的芯片上真皮模型在化合物筛选中的实用性。
