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Cardiac tissue engineering and disease modeling

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The high prevalence of heart disease worldwide partially arises from the myocardium’s limited capacity to regenerate after injury. While existing therapies can alleviate some of the symptoms, there are no treatments that restore cardiac function following injury from myocardial infarction or adverse remodeling caused by chronic cardiomyopathies. Thus, there is a pressing need to engineer heart tissue (EHT) for use in regenerative therapies or as in vitro models of cardiac disease. Our lab utilizes microfabrication techniques and synthetic biomaterials that mimic the complex structure of the cardiac ECM to create adult stem-cell derived EHTs with defined biochemical, architectural, and mechanical properties. Additionally, we’re working on technologies to pattern microvasculature within these tissues, which is essential given the high metabolic demand of the myocardium.  Short of our long-term interest in engineering a functional cardiac patch, we also use our EHT platforms to study how the specific microenvironmental cues drive cardiac tissue development, homeostatic function, and how pathological alterations to the cardiac microenvironment lead to tissue dysfunction and disease-associated signaling.  Our work in this space is sponsored by the NSF through our involvement in the NSF CELL-MET Engineering Research Center.

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Sam's FibroTUG platform for generating contractile hiPSC-CM EHTs on tunable synthetic fibrous matrices. 

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Maggie's sacrificial microfiber approach to generating capillary-scale vasculature. 

Trainees:  Maggie Jewett, Samuel DePalma
Collaborators:  Adam Helms, David Nordsletten
Relevant publications:
Matrix architecture and mechanics regulate myofibril organization, costamere assembly, and contractility of engineered myocardial microtissues
DePalma SJ, Jillberto J, Stis AE, Huang DD, Lo J, Davidson CD, Chowdhury A, Jewett ME, Kobeissi H, Chen CS, Lejeune E, Helms AS, Nordsletten DA, Baker BM.
BioRxiv. 2023 Oct. doi.org/10.1101/2023.10.20.563346
Rapid Magnetically Directed Assembly of Pre-Patterned Capillary-Scale Microvessels
Jewett ME, Hiraki HL, Wojasiński M, Zhang Z, Xi SS, Bluem AS, Prabhu ES, Wang WY, Pena‐Francesch A, Baker BM.
Advanced Functional Materials. 2023 Jun:2203715.  doi/10.1002/adfm.202203715

Physiologic biomechanics enhance reproducible contractile development in a stem cell derived cardiac muscle platform

Tsan YC, DePalma SJ, Zhao YT, Capilnasiu A, Wu YW, Elder B, Panse I, Ufford K, Matera DL, Friedline S, O'Leary TS, Wubshet N, Ho KKY, Previs MJ, Nordsletten D, Isom LL, Baker BM, Liu AP, Helms AS.
Nature Communications. 2021 Oct 25;12(1):6167. PMID: 34697315; PMCID: PMC8546060.
Microenvironmental determinants of organized iPSC-cardiomyocyte tissues on synthetic fibrous matrices
DePalma SJ, Davidson CD, Stis AE, Helms AS, Baker BM.
Biomaterials Science, 2021 Jan 5;9(1):93-107. PMID: 33325920; PMCID: PMC7971708.
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