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When built into engineered tissues, the gel derived cardiomyocytes still showed improved structural maturity. www.biorxiv.org/content/10.6... We are excited to share this work with the research community!

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*Cardiomyocytes produced this showed some hallmarks of structural maturity rarely achieved in standard 2D culture, including robust, properly organized expression of Desmin, a key cardiac structural protein.

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*Tuning the gel's stiffness mattered just as much as its biochemistry. Softer gels supported greater stem cell expansion and yielded significantly more, purer cardiomyocytes than stiffer formulations.

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* Xeno-free gel platform without animal-derived materials that have long complicated clinical translation of stem cell-derived heart cells. * Integrin-binding peptides (cyclic RGD) were essential for iPSC survival and pluripotency inside the gel, though only a low dose was required

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Mohammadjafar's approach proved not only to be a robust, scalable way to make the cardiomyocytes, but also produced cardiomyocytes with higher structural maturity. Highlights of the work include:

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Excited to share this preprint from Postdoctoral Fellow and future Professor Mohammadjafar (MJ) Hashemi, who used defined alginate gels to develop an iPSC-cardiomyocyte biomanufacturing platform system!

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Yasaman also studied the potential of the JAK inhibitor Itacitinib to treat desmin-related cardiomyopathy. lnkd.in/gigbcdNn

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we found that within micro-tissues, iPSC-cardiomyocytes expressed desmin, and mutations that impact protein quality control impact both desmin organization and tissue-level contractility.

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Finally, in elegant work led by PhD student Yasaman Kargar, we leveraged our new micro-engineered heart tissue models to study desmin-related cardiomyopathy. With key contributions from our collaborator Abhinav Diwan, MD, FACC, FAHA,

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PDMS-post based tissues with arbitrary geometry and leveraged this to study the dynamics of nuclear and cell shape changes, and subsequent activation, on the fibroblast-to-myofibroblast transition: lnkd.in/gfME2pC6 . Congrats to Ghiska and team.

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In the second story, in a BioRxiv preprint led by PhD student alumnus Ghiska Ramahdita, we studied the impact of tensional anisotropy on fibroblast activation. We developed a second-generation version of Hydrogel Assisted STereolithographic Elastomer (HASTE) prototyping to create

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This work, published in Biofabrication iopscience.iop.org/article/10.1... that progenitors, which may be easier to use for biomanufacturing, could be used instead of fully differentiated cardiomyocytes.

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from iPSC-derived cardiomyocytes or iPSC-derived cardiovascular progenitors. To our surprise, there were no significant differences in physiology, morphology or gene expression when the tissues were aged to a common timepoint.

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