Song Yuanhui, Seitz Michael, Kowalczewski Andrew, Mai Nhu Y, Jain Era, Yang Huaxiao, Ma Zhen
Department of Biomedical & Chemical Engineering, Syracuse University, Syracuse, NY, 13244, USA.
BioInspired Institute for Material and Living Systems, Syracuse University, Syracuse, NY, 13244, USA.
Adv Healthc Mater. 2025 Jun;14(16):e2403997. doi: 10.1002/adhm.202403997. Epub 2025 May 16.
Cardioids are 3D self-organized heart organoids directly derived from induced pluripotent stem cells (hiPSCs) aggregates. The growth and culture of cardioids is either conducted in suspension culture or heavily relies on Matrigel encapsulation. Despite the significant advancements in cardioid technology, reproducibility remains a major challenge, limiting their widespread use in both basic research and translational applications. Here, for the first time, we employed synthetic, matrix metalloproteinase (MMP)-degradable polyethylene glycol (PEG)-based hydrogels to define the effect of mechanical and biochemical cues on cardioid development. Successful cardiac differentiation is demonstrated in all the hydrogel conditions, while cardioid cultured in optimized PEG hydrogel (3 wt.% PEG-2mM RGD) underwent similar morphological development and comparable tissue functions to those cultured in Matrigel. Matrix stiffness and cell adhesion motif play a critical role in cardioid development, nascent chamber formation, contractile physiology, and endothelial cell gene enrichment. More importantly, synthetic hydrogel improved the reproducibility in cardioid properties compared to traditional suspension culture and Matrigel encapsulation. Therefore, PEG-based hydrogel has the potential to be used as an alternative to Matrigel for human cardioid culture in a variety of clinical applications including cell therapy and tissue engineering.
类心脏球体是直接从诱导多能干细胞（hiPSC）聚集体中衍生出来的3D自组织心脏类器官。类心脏球体的生长和培养要么在悬浮培养中进行，要么严重依赖基质胶包封。尽管类心脏球体技术取得了重大进展，但可重复性仍然是一个主要挑战，限制了它们在基础研究和转化应用中的广泛使用。在这里，我们首次使用了基于合成的、可被基质金属蛋白酶（MMP）降解的聚乙二醇（PEG）水凝胶来确定机械和生化信号对类心脏球体发育的影响。在所有水凝胶条件下均证明了成功的心脏分化，而在优化的PEG水凝胶（3 wt.% PEG-2mM RGD）中培养的类心脏球体与在基质胶中培养的类心脏球体经历了相似的形态发育和相当的组织功能。基质硬度和细胞黏附基序在类心脏球体发育、新生腔室形成、收缩生理学和内皮细胞基因富集方面起着关键作用。更重要的是，与传统的悬浮培养和基质胶包封相比，合成水凝胶提高了类心脏球体特性的可重复性。因此，基于PEG的水凝胶有潜力在包括细胞治疗和组织工程在内的各种临床应用中作为基质胶的替代品用于人类类心脏球体培养。
