Zlotnick Hannah M, Goddard Declan N, Calo Christopher J, Dhand Abhishek P, Davidson Matthew D, Solsona-Pujol Aina, Weppner Hannah K, Wong Melissa, Scanzello Carla R, Hind Laurel E, Burdick Jason A
BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80303, USA.
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
bioRxiv. 2025 Jul 17:2025.07.12.664530. doi: 10.1101/2025.07.12.664530.
Most patients who sustain an acute joint injury develop degenerative joint disease, or osteoarthritis (OA). Animal models have informed the design of OA therapeutics; however, no disease-modifying therapy has successfully translated to human patients. Thus, there is a strong motivation to develop humanized platforms to fill a critical gap in knowledge of disease progression post-injury. Here, we develop an acute injury-on-a-chip model of the synovium, a vascularized, joint-lining tissue that has been implicated in OA progression and as a key driver of joint disease. We apply this chip-based system to investigate crosstalk between endothelial cells, lining an engineered vessel, and synovial fibroblasts, embedded within an extracellular matrix hydrogel. Our data indicate that synovial fibroblasts, rather than initiating disease, attempt to support and maintain vascular function in the presence of acute inflammation (i.e., interleukin-1β). Such knowledge may provide new targets for OA therapeutics, preventing the progression from joint injury to disease in patients.
大多数遭受急性关节损伤的患者会发展为退行性关节疾病，即骨关节炎（OA）。动物模型为骨关节炎治疗方法的设计提供了依据；然而，尚无改善病情的疗法成功应用于人类患者。因此，开发人性化平台以填补损伤后疾病进展知识的关键空白具有强烈的动机。在此，我们开发了一种滑膜的急性损伤芯片模型，滑膜是一种血管化的关节衬里组织，与骨关节炎的进展有关，并且是关节疾病的关键驱动因素。我们应用这个基于芯片的系统来研究在内皮细胞（排列在工程血管内）和滑膜成纤维细胞（嵌入细胞外基质水凝胶中）之间的相互作用。我们的数据表明，滑膜成纤维细胞并非引发疾病，而是在急性炎症（即白细胞介素-1β）存在的情况下试图支持和维持血管功能。这些知识可能为骨关节炎治疗提供新的靶点，防止患者从关节损伤发展为疾病。
