![]() ![]() Recreating the material and cellular properties of adult cardiac tissue has proven to be a complex engineering challenge ( Burnham et al., 2020 Patino-Guerrero et al., 2020). Therefore, human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) have been used to develop engineered heart tissues (EHTs), with the ultimate goal of using in vitro grown tissues to surgically repair injured human hearts ( Bargehr et al., 2017 Gerbin & Murry, 2015 Tohyama & Fukuda, 2016 Tzahor & Poss, 2017 Uygur & Lee, 2016). ![]() Although heart transplantation can address end-stage heart failure, organ shortages limit therapeutic availability. ![]() The adult human heart is unable to naturally recover from severe traumatic, ischemic, or chronic damage, due to its limited regenerative potential ( Urbanek et al., 2005 Xin et al., 2013). Our work highlights the critical role of mechanical conditioning as an important engineering strategy toward developing clinically applicable, scaffold-free human cardiac tissue grafts. Taken together, our results suggest that mechanical stretching stimulates hiPSC-derived CMs in a 3D-printed, scaffold-free tissue graft to develop mature cardiac material structuring and cellular fates. Finally, analysis of extracellular matrix organization in stretched grafts suggests improved remodeling by embedded cardiac fibroblasts. Additionally, stretched tissues had upregulated expression of cardiac-specific gene transcripts, consistent with increased cardiac-like cellular identity. Stretched tissue was found to have decreased elastic modulus, increased maximal contractile force, and increased alignment of formed extracellular matrix, as expected in a functionally maturing tissue graft. Static mechanical stretching of these grafts significantly increased sarcomere length compared to unstimulated free-floating tissues, as determined by immunofluorescent image analysis. To explore this, we used a 3D bioprinter to produce scaffold-free cardiac tissue grafts from hiPSC-derived CM cell spheroids. Therefore, the goal of our study was to create scaffold-free, 3D-printed cardiac tissue grafts from hiPSC-derived cardiomyocytes (CMs), and to evaluate whether or not mechanical stimulation would result in improved graft maturation. However, any imbalance in the interactions between embedded cells and their surroundings may hinder the success of the resulting tissue graft. Current efforts to engineer a clinically relevant tissue graft from human-induced pluripotent stem cells (hiPSCs) have relied on the addition or utilization of external scaffolding material. ![]()
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