Research overview

The Ogle Lab is pushing the boundaries of 3D bioprinting for cardiac tissue engineering to create complex model systems that extend well beyond the “wood piles” and simple geometric shapes prevalent in the literature. This work is enabled by basic studies to understand the interplay between the extracellular matrix, pluripotent stem cells and associated cardiac progeny.

Outcomes of these studies pointed us to unique bioink formulations that can be coupled with multiphoton-based 3D printing to create patch-like structure with features on the scale of a single micron. Patches of this type support cardiac cell organization, can be easily adhered to the failing heart, and have been used successfully in rodent models of cardiac failure to restore function. Large animal studies are ongoing.

In other work, novel, extracellular matrix-based bioinks have also been used to fabricate living, complex, chambered heart structures based on a digital template of the human heart taken via MRI and scaled to the size of a mouse heart (graphic). The chambered structure was printed using the bioink with human induced pluripotent stem cells. The stem cells undergo expansion and differentiation to cardiac muscle after printing to yield structures containing exclusively cardiac cell types and capable of synchronous beating, which can be accelerated with electrical pacing.

To date, we have measured clinically-important, physiologically complex mechanical parameters including pressure dynamics not possible with cardiac microtissues (microscale strips of cardiac muscle and current state of the art) and associated electrical parameters including action potential, calcium transients, and conduction velocity. The utility of this work for the field of cardiology is access to a human model system that can sustain flow profiles and exhibit pressure-volume dynamics characteristic of the native heart.

This model will therefore be useful for understanding remodeling associated with cardiac disease progression imposed by mechanical insult, genetic predisposition, or diet. It will also be useful for testing drug toxicity or efficacy and, given the scale, is amenable to the testing of medical devices and implantation to the heterotopic position in mice and perhaps one day for human transplantation.

Lab website

Education

• BS, Mathematics and Natural Science, College of St. Benedict/St. John's University, 1994
• MS, Biomedical Engineering, University of Minnesota-Twin Cities, 1998
• PhD, Biomedical Engineering, University of Minnesota-Twin Cities, 2000
• Postdoctoral Fellow, Mayo Clinic College of Medicine

Teaching Subjects

• Biomaterials
• Tissue Engineering
• Cell and Molecular Biology for Biomedical Engineers
• Biomedical Design

Currently Teaching Courses

• BMEn 5031 Engineering Extracellular Matrices
• BMEn 8041 Advanced Tissue Engineering Lab
• BMEn 1601/2 First Year Biomedical Engineering Seminar

Honors and Awards

• National Institutes of Health Training Fellowship, Mayo Clinic Digestive Disease (2001, 2002)       
• National Institutes of Health Training Fellowship, Mayo Clinic Nephrology (2003, 2004) 
• National Institutes of Health Mentored Career Award (2004)
• Polygon Outstanding Professor Award, UW-Madison, College of Engineering (2007)     
• Edward P. Mikol Best Paper Award, American Society for Engineering Education (2008)
• National Science Foundation CAREER Award (2009)
• Distinguished Lecturer, Department of Chemical Engineering, Michigan Technological University, MI (2011)
• Women’s Faculty Cabinet, Provost Office, Co-Chair Elect (2014-2016)
• Tony Diggs Award for Excellent Graduate Student Group, Advisor (2015, 2019)
• Regenerative Medicine Minnesota, Inaugural Year Awardee, Biobusiness and Biotechnology (2015) 
• Mullen-Spector-Truax Women’s Leadership Award (2016)
• American Institute for Medical and Biological Engineering, Elected Fellow (2017)
• Best Manuscript Award, Circulation Research (Impact Factor 15.9) (2021)
• Biomedical Engineering Society, Elected Fellow (2021)  

Selected Publications

Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering.
Singh BN, Yucel D, Garay BI, Tolkacheva EG, Kyba M, Perlingeiro RCR, van Berlo JH, Ogle BM.Circ Res. 2023 Feb 17;132(4):519-540. doi: 10.1161/CIRCRESAHA.122.321770. Epub 2023 Feb 16.PMID: 36795845 Review.

Lysosomal Ca²⁺ flux modulates automaticity in ventricular cardiomyocytes and correlates with arrhythmic risk.
Xie A, Kang GJ, Kim EJ, Feng F, Givens SE, Ogle BM, Dudley SC Jr.PNAS Nexus. 2023 May 25;2(6):pgad174. doi: 10.1093/pnasnexus/pgad174. eCollection 2023 Jun.PMID: 37303713 Free PMC article.  

A Bionic Testbed for Cardiac Ablation Tools.
Lin WH, Zhu Z, Ravikumar V, Sharma V, Tolkacheva EG, McAlpine MC, Ogle BM.Int J Mol Sci. 2022 Nov 21;23(22):14444. doi: 10.3390/ijms232214444.PMID: 36430922 Free PMC article.

Myosin Heavy Chain Converter Domain Mutations Drive Early-Stage Changes in Extracellular Matrix Dynamics in Hypertrophic Cardiomyopathy.
Hsieh J, Becklin KL, Givens S, Komosa ER, Lloréns JEA, Kamdar F, Moriarity BS, Webber BR, Singh BN, Ogle BM.Front Cell Dev Biol. 2022 Jun 16;10:894635. doi: 10.3389/fcell.2022.894635. eCollection 2022.PMID: 35784482 Free PMC article.

Laminin 411 mediates endothelial specification via multiple signaling axes that converge on β-catenin.
Hall ML, Givens S, Santosh N, Iacovino M, Kyba M, Ogle BM.Stem Cell Reports. 2022 Mar 8;17(3):569-583. doi: 10.1016/j.stemcr.2022.01.005. Epub 2022 Feb 3.PMID: 35120622 Free PMC article.

Kinases of the Focal Adhesion Complex Contribute to Cardiomyocyte Specification.
Robert S, Flowers M, Ogle BM.Int J Mol Sci. 2021 Sep 28;22(19):10430. doi: 10.3390/ijms221910430.PMID: 34638793 Free PMC article.

Implementing Biological Pacemakers: Design Criteria for Successful.
Komosa ER, Wolfson DW, Bressan M, Cho HC, Ogle BM.Circ Arrhythm Electrophysiol. 2021 Oct;14(10):e009957. doi: 10.1161/CIRCEP.121.009957. Epub 2021 Oct 1.PMID: 34592837 Free PMC article. Review.

In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.
Kupfer ME, Lin WH, Ravikumar V, Qiu K, Wang L, Gao L, Bhuiyan DB, Lenz M, Ai J, Mahutga RR, Townsend D, Zhang J, McAlpine MC, Tolkacheva EG, Ogle BM.Circ Res. 2020 Jul 3;127(2):207-224. doi: 10.1161/CIRCRESAHA.119.316155. Epub 2020 Mar 31.PMID: 32228120 Free PMC article.

Breast tumor cell hybrids form spontaneously in vivo and contribute to breast tumor metastases.
Chitwood CA, Dietzsch C, Jacobs G, McArdle T, Freeman BT, Banga A, Noubissi FK, Ogle BM.APL Bioeng. 2018 Aug 7;2(3):031907. doi: 10.1063/1.5024744. eCollection 2018 Sep.PMID: 31069316 Free PMC article.

Conserved pathway activation following xenogeneic, heterotypic fusion.
Yuan C, Freeman BT, McArdle TJ, Jung JP, Ogle BM.
FASEB J. 2019 Jun;33(6):6767-6777.

Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure.
Berry JL, Zhu W, Tang YL, Krishnamurthy P, Ge Y, Cooke JP, Chen Y, Garry DJ, Yang HT, Rajasekaran NS, Koch WJ, Li S, Domae K, Qin G, Cheng K, Kamp TJ, Ye L, Hu S, Ogle BM, Rogers JM, Abel ED, Davis ME, Prabhu SD, Liao R, Pu WT, Wang Y, Ping P, Bursac N, Vunjak-Novakovic G, Wu JC, Bolli R, Menasché P, Zhang J.
Circ Res. 2019 Jan 4;124(1):161-169.

Breast tumor cell hybrids form spontaneously in vivo and contribute to breast tumor metastases.
Chitwood CA, Dietzsch C, Jacobs G, McArdle T, Freeman BT, Banga A, Noubissi FK, Ogle BM.
APL Bioeng. 2018 Aug 7;2(3):031907.

Cardiac Extracellular Matrix Modification as a Therapeutic Approach.
Hall ML, Ogle BM.
Adv Exp Med Biol. 2018;1098:131-150.

A 3D in vitro model of the dermoepidermal junction amenable to mechanical testing.
Jung JP, Lin WH, Riddle MJ, Tolar J, Ogle BM.
J Biomed Mater Res A. 2018 Dec;106(12):3231-3238.

Myocardial Tissue Engineering With Cells Derived From Human-Induced Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold.
Gao L, Kupfer ME, Jung JP, Yang L, Zhang P, Da Sie Y, Tran Q, Ajeti V, Freeman BT, Fast VG, Campagnola PJ, Ogle BM, Zhang J.
Circ Res. 2017 Apr 14;120(8):1318-1325.

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues.
Borovjagin AV, Ogle BM, Berry JL, Zhang J.
Circ Res. 2017 Jan 6;120(1):150-165.

Distilling complexity to advance cardiac tissue engineering.
Ogle BM, Bursac N, Domian I, Huang NF, Menasché P, Murry CE, Pruitt B, Radisic M, Wu JC, Wu SM, Zhang J, Zimmermann WH, Vunjak-Novakovic G.
Sci Transl Med. 2016 Jun 8;8(342):342ps13.

Single-cell RNA-seq reveals activation of unique gene groups as a consequence of stem cell-parenchymal cell fusion.
Freeman BT, Jung JP, Ogle BM.
Sci Rep. 2016 Mar 21;6:23270.