METHACRYLATED HUMAN RECOMBINANT COLLAGEN PEPTIDE AS A HYDROGEL FOR MANIPULATING AND MONITORING STIFFNESS-RELATED CARDIAC CELL BEHAVIOR by Mostert et al

Environmental stiffness is a crucial determinant of cell function. There is a longstanding quest for reproducible and (human matrix)bio-mimicking biomaterials with controllable mechanical properties to unravel the relationship between stiffness and cell behavior. Here, we evaluate methacrylated human recombinant collagen peptide (RCPhC1-MA) hydrogels as a matrix to control 3D microenvironmental stiffness and monitor cardiac cell response. We show that RCPhC1-MA can form hydrogels with reproducible stiffness in the range of human developmental and adult myocardium. Human cardiomyocytes (CMs) and cardiac fibroblasts (cFBs) remain viable up to 14 days in RCPhC1-MA hydrogels while the effect of hydrogel stiffness on extracellular matrix production and CM contractility can be monitored in real time. Interestingly, whereas the beating behavior of the CM monocultures is affected by environmental stiffness, this effect ceases when cFBs are present. Together, we demonstrate RCPhC1-MA to be a promising candidate to mimic and control the 3D environment of cardiac cells.环境刚度是决定细胞功能的关键因素。长期以来，学界一直致力于开发可重复、具备可控力学性能的（人源基质）仿生生物材料，以阐明刚度与细胞行为之间的关联。本研究评估了甲基丙烯酸酯化人源重组胶原蛋白肽（RCPhC1-MA）水凝胶作为基质，用于调控三维微环境刚度并监测心肌细胞响应的潜力。结果表明，RCPhC1-MA可形成刚度可重复且处于人类发育性及成人心肌组织范围内的水凝胶。人心肌细胞（CMs）与心脏成纤维细胞（cFBs）在RCPhC1-MA水凝胶中可存活长达14天，且可实时监测水凝胶刚度对细胞外基质分泌及心肌细胞收缩性的影响。有趣的是，尽管心肌细胞单培养体系的搏动行为受环境刚度影响，但当体系中存在心脏成纤维细胞时，该效应会消失。综上，本研究证实RCPhC1-MA是模拟并调控心肌细胞三维微环境的极具潜力的候选材料。