Heart-Muscle-on-Chip
As cardiovascular diseases constitute a dominant cause of death, engineered cardiac tissues created by induced pluripotent stem (iPS) cells are being intensively investigated for applications in drug screening, disease modeling or personalized medicine. The integration of cardiac tissues into microphysiological platforms led to the emergence of a variety of Heart-on-a-Chip systems which are able to generate viable, functionally beating 3D microtissues in a controlled environment. However, most of these systems either lack the ability to analyze the integrated tissues in a quantitative way or lack a physiological supply of the tissue via a vasculature-like perfusion. The aim of this project is to develop and optimize Heart-on-a-Chip systems by providing a platform for the parallelized perfused cultivation and analysis of a large number of individual cardiac tissues. The platform will thereby enable the in situ quantification of characteristics such as beat rate and contractile forces. Additionally, capacities allowing electrical stimulation and oxygen and pH sensing will be implemented.
Heart-Valve-on-Chip
Valvular heart diseases (VHDs) affect the function of the heart valves, which is the regulation of the blood flow into and out of the heart. Diseased heart valves can become too narrow and hardened to open fully or the valve is unable to close properly, causing the blood to leak backward. The progression of VHDs can lead to further complications and it is often associated with heart failure because the damaged valve causes the heart to pump harder in order to force the blood, which can lead to atrial fibrillation or eventually the complete failure of the heart. Moreover, a damaged valve is also significantly more sensitive to infections. Therefore, VHDs are a growing burden on the health care system, associated with high morbidity and mortality. Especially in the case of advanced VHDs, there are often no drug therapies to cure, regenerate or stop the progression of this disease. Microfluidic heart valve-on-a-chip systems have the potential to replicate both structure and functionality and thus to study influences of the dynamic environment on biomechanics and tissue formation as well as pathological effects. The aim of the project is therefore the integration of different biofunctional carrier substrates into a microfluidic systems to create representative microphysiological environments.
Funding: H2020 - MSCA ITN EUROoC; BW Foundation;
Publications
O. Schneider, A. Moruzzi, S. Fuchs, A. Grobel, H.S. Schulze, T. Mayr, P. Loskill
Fusing spheroids to aligned μ-tissues in a heart-on-chip featuring oxygen sensing and electrical pacing capabilities
Mater. Today Bio, 2022, 15, 100280, https://doi.org/10.1016/j.mtbio.2022.100280
U. Arslan*, A. Moruzzi*, J. Nowacka*, C. Mummery°, D. Eckardt°, P. Loskill°, V. Orlova°
Microphysiological stem cell models of the human heart
Mater. Today Bio, 2022, 14, 100259, https://doi.org/10.1016/j.mtbio.2022.100259
K. Stadelmann, A. Weghofer, M. Urbanczyk, I.T. Maulana, P. Loskill, P.D. Jones, K. Schenke-Layland
Development of a bi-layered cryogenic electrospun polylactic acid scaffold to study calcific aortic valve disease in a 3D co-culture model
Acta Biomater., 2022, 140, 364-378, https://doi.org/10.1016/j.actbio.2021.11.030
O. Schneider, L. Zeifang, S. Fuchs, C. Sailer, P. Loskill
User-friendly and paralleled generation of hiPSC-derived μ-tissues in a centrifugal heart-on-a-chip
Tissue Eng., 2019, 25, 786-798, https://doi.org/10.1089/ten.TEA.2019.0002
A. Ryan, C. Kearney, N. Shen, U. Khan, A. Kelly, C. Probst, E. Brauchle, S. Biccai, C. Garciarena, V. Vega-Mayoral, P. Loskill, S. Kerrigan, D. Kelly, K. Schenke-Layland, J. Coleman, F. J. O’Brien
Electroconductive Biohybrid Collagen/Pristine Graphene Composite Biomaterials with Enhanced Biological Activity
Adv. Mater., 2018, 30, 1706442, https://doi.org/10.1002/adma.201706442
N. Huebsch, P. Loskill, N. Deveshwar, C.I. Spencer, L. Judge, M.A. Mandegar, C. Fox, T. Mohammed, Z. Ma, A. Mathur, A.S. Sheehan, A. Truong, M. Saxton, J. Yoo, D. Srivastava, T.A. Desai, P.-L. So, K.E. Healy, B. R. Conklin
Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses
Sci. Rep., 2016, 6, 24726, http://www.dx.doi.org/10.1038/srep24726
A. Mathur, Z. Ma, P. Loskill, S. Jeeawoody, K.E. Healy
In Vitro Cardiac Tissue Models: Current Status and Future Prospects
Adv. Drug. Deliv. Rev., 2016, 96, 203-213, http://www.dx.doi.org/10.1016/j.addr.2015.09.011
