Robert T. Tranquillo, PhD

Department Head, Department of Biomedical Engineering

Robert T. Tranquillo

Contact Info

tranquil@umn.edu

Office Phone 612-625-6868

Office Address:
Biomedical Engineering
7-114 NHH
312 Church St SE
Minneapolis, MN 55455

Mailing Address:
Biomedical Engineering
Room 7-105 NHH
1191L (Campus Delivery Code)
312 Church St SE
Minneapolis, MN 55455

Department Head, Department of Biomedical Engineering

McKnight University Distinguished Professor


Postdoctoral Fellow, Oxford University (Mathematical Biology), 1987

PhD, University of Pennsylvania (Chemical Engineering), 1986

MS, Stanford University (Chemical Engineering), 1980

BS, Pennsylvania State University (Chemical Engineering), 1979

Summary

Prof. Tranquillo received his Ph.D. in Chemical Engineering in 1986 from the University of Pennsylvania. He was a NATO Postdoctoral Fellow at the Center for Mathematical Biology at Oxford for one year before beginning his appointment in the Department of Chemical Engineering & Materials Science at the University of Minnesota in 1987. He has served as the head of the Department of Biomedical Engineering since its inception in 2000. Prof. Tranquillo has used a combined modeling and experimental approach to understand cell behavior, in particular, directed cell migration, and cell-matrix mechanical interactions. More recently, his research program has focused on the role of these cell behaviors in cardiovascular and neural tissue engineering applications. His research program has resulted in over 100 peer-reviewed original research publications as first or senior author, being recognized with his selection for the TERMIS-AM Senior Scientist Award in 2015. Prof. Tranquillo is a Fellow of the American Institute of Medical and Biological Engineering, International Academy of Medical and Biological Engineering, and the Biomedical Engineering Society, and he is also a Distinguished McKnight University Professor.

Research

Research Summary/Interests

Cardiovascular Tissue Engineering

In the area of cardiovascular tissue engineering, we have developed the use of the "tissue-equivalent" as a replacement for a diseased or damaged small diameter artery, heart valve, and myocardium. Tissue-equivalents are fabricated from entrapping the relevant tissue cell into a biopolymer gel and constraining the cell-mediated gel compaction to engineer the alignment of the gel fibrils, so as to mimic the alignment of the target tissue. In prior work we have extensively researched the process by which cell traction exerted on gel fibrils by cells causes fibril reorganization on the microscale and contraction of the fibril network on the macroscale, inducing fibril alignment and thereby cell contact guidance in a complicated but fascinating biomechanical feedback loop. This understanding guides the design of molds presenting appropriate mechanical constraints for fabrication of tissue-equivalents with prescribed alignment.

Our current research in cardiovascular tissue engineering focuses on the use of fibrin gel as an alternative to the traditional use of collagen gel because of the extensive compositional remodeling that can be realized in addition to the structural remodeling described above. Major questions are how do the collagen fibrils and elastic fibers being produced depend on exposure to cyclic mechanical stretching, transmural flow, and soluble chemical stimuli? Bioreactors are being developed and used to answer these questions. A related question is how does the resultant tissue composition and structure translate into functional properties of interest, such as proper compliance and sufficient burst pressure for our artery-equivalent or bending properties of the leaflets in our valve-equivalent? In order to address such questions in tissue growth and remodeling, we have developed a high-speed tissue alignment imaging system that we are using in conjunction with biaxial mechanical testing and electron microscopy of tissue-equivalents with systematically varied composition and alignment (with Prof. Victor Barocas).

The more complicated geometry and mechanical function related to leaflet bending for valve opening and closing poses new challenges being addressed in a collaborative effort to relate optimal mold design to ultimate function of the valve-equivalent (with Profs. Barocas, Ellen Longmire, and Fotis Sotiropoulos). We are developing a novel controlled-stretch bioreactor and use of photo-crosslinked fibrin as complementary strategies to achieve greater bending stiffness and strength of the valve leaflets. A newer project similarly seeks to generate a myocardium-equivalent, or 'heart patch', by exploiting the contact guidance features of tissue-equivalent fabrication to attain requisite electro-mechanical function (with Prof. Jay Zhang). A distinctive feature of our heart patch is creating a self-assembled network of dense and aligned microvessels that allows for efficient nutrient transport (with George Davis, U Missouri)

In all these projects, the use of blood-derived endothelial cells (with Profs. Robert Hebbel and Gregory Vercellotti) and mesenchymal stem cells (with Prof. Jakub Tolar) is being explored to provide a quiescent endothelium at implantation and possibly a functional microvasculature within the tissue as well. Also, animal studies are also being conducted (with Experimental Surgical Services).

Contact guidance -- the ability of cells to sense and aligned with aligned fibers -- is crucial to our ability to create tissues with prescribed alignment. The underlying mechanism of contact guidance is being investigated using methods, including magnetic alignment and photo-crosslinking of fibrin, to systematically vary the chemical/physical cues contained in aligned fibers that cells might be sensing (with Prof. Elliot Botvinick, UC-Irvine).

Publications

Selected Publications

  • Cyclic stretch and perfusion bioreactor for conditioning large diameter engineered tissue tubes. Schmidt, J.B. and R.T. Tranquillo. Ann Biomed Eng (accepted).
  • Functional consequences of a tissue-engineered cardiac patch from human induced pluripotent stem cell-derived cardiomyocytes in a rat infarct model. Wendel, J., Ye, L., Rao, T. Zhang, J., Zhang, J., Kamp, T.J. and R.T. Tranquillo. STEM CELLS Transl Med (accepted).
  • The effects of intermittent versus incrementally increasing strain magnitude cyclic stretching on ERK signaling and collagen production in engineered tissue. Schmidt, J.B. and R.T. Tranquillo. Cell Molec Bioeng (accepted).
  • Pediatric tubular pulmonary heart valve from decellularized engineered tissue tubes. Reimer, J.M., Syedain, Z.H., Haynie, B and R.T. Tranquillo. Biomaterials 62: 88-94 (2015). (abstract)
  • Automated image analysis programs for the quantification of microvascular network characteristics. Morin, K.T., Carlson, P. C. and R. T. Tranquillo. Methods 84: 76-83 (2015). (abstract)
  • A mathematical model for understanding fluid flow through engineered tissues containing microvessels. Morin, K.T., Lenz, M.S., Labat, C. and R.T. Tranquillo . J Biomech Eng 137: 051003 (2015). (abstract)
  • Influence of culture conditions and extracellular matrix alignment on human mesenchymal stem cell invasion into decellularized engineered tissues. Weidenhamer, N.K., Moore, D.L., Lobo, F.L., Klair, N.T. and R.T. Tranquillo. J Tissue Eng Regen Med 9: 605-18 (2015). (abstract)
  • Engineered microvessels possessing alignment and high lumen density via cell-induced fibrin gel compaction and interstitial flow. Morin, K.T., Dries-Devlin, J.L. and R.T. Tranquillo. Tissue Eng Part A 20: 553-65 (2014). (abstract)
  • Functional consequences of a tissue-engineered myocardial patch for cardiac repair in an acute rat infarct model. Wendel, J., Ye, L., Zhang, P., Tranquillo, R.T. and J. Zhang
  • Tissue Eng Part A 20: 1325-35 (2014). (abstract)
  • Implantation of completely biological engineered grafts following decellularization into the sheep femoral artery. Syedain, Z.H., Meier, L.A., Lahti, M.T., Johnson, S.L., Hebbel, R.P and R. T. Tranquillo. Tissue Eng Part A 20: 1726-34 (2014). (abstract)
  • Blood Outgrowth Endothelial Cells Alter Remodeling of Completely Biological Engineered Grafts Implanted into the Sheep Femoral Artery. Meier, L.A., Syedain, Z.H., Lahti, M.T., Johnson, S.L., Chen, M.H., Hebbel, R.P and R. T. Tranquillo. J Cardiovasc Trans Res A 7: 242-9 (2014). (abstract)
  • A multiscale approach to modeling the passive mechanical contribution of cells in tissues. Lai, V.K., Hadi, M.F., Tranquillo, R.T., and V.H. Barocas. J Biomech Eng 135(7): 71007 (2013). (abstract)
  • Combating adaptation to cyclic stretching by prolonging activation of extracellular signal-regulated kinase. Weinbaum, J.S., Schmidt, J.B., and R.T. Tranquillo. Cell Molec Bioeng 6(3): 279-86 (2013). (abstract)
  • Aligned human microvessels formed in 3D fibrin gel by constraint of gel contraction. Morin, K.T., Smith, A.O., Davis, G.E., and R.T. Tranquillo. Microvasc Res 90:12-22 (2013). (abstract)
  • Tubular heart valves from decellularized engineered tissue. Syedain, Z.H., Meier, L.A., Reimer, J., and R.T. Tranquillo. Ann Biomed Eng 41(12): 2645-54 (2013). (abstract)
  • Influence of cyclic mechanical stretch and tissue constraints on cellular and collagen alignment in fibroblast-derived cell sheets. Weidenhamer, N.K and R.T. Tranquillo
  • Tissue Eng Part C 19(5): 386-95 (2013). (abstract)
  • Decellularized tissue-engineered heart valve leaflets with recellularization potential. Syedain, Z.H., Bradee, A.R., Kren S., Taylor, D.A. and R.T. Tranquillo. Tissue Eng Part A 19:759 (2013). (abstract)
  • Microstructural and mechanical differences between digested collagen-fibrin co-gels and pure collagen and fibrin gels. Lai, V. K, Frey, C.R., Kerandi, A.M., Lake, S. P., Tranquillo, R.T. and V.H. Barocas. Acta Biomat 8:4031 (2012). (abstract)
  • Mechanical behavior of collagen-fibrin co-gels reflect transition from series to parallel interactions with increasing collagen content. Lai, V. K, Lake, S. P., Frey, C.R., Tranquillo, R.T. and V.H. Barocas. J Biomech Eng 134: 011004-1 (2012). (abstract)
  • Hypoxic Culture and Insulin Yield Improvements to Fibrin-Based Engineered Tissue. Bjork, J.W., Meier, L.A., Johnson, S.L., Syedain, Z.H., and R.T. Tranquillo. Tissue Eng Part A, 18(7-8): 785-795 (2012). (abstract)
  • Shear stress responses of adult blood outgrowth endothelial cells seeded on bioartifical tissue. Ahmann, K. A., Johnson, S. L., Hebbel, R.P. and R.T. Tranquillo. Tissue Eng Part A 17:2511 (2011). (cover photo) (abstract)
  • Guided sprouting from endothelial spheroids in fibrin gels aligned by magnetic fields and cell-induced gel compaction. Morin, K.T. and R.T. Tranquillo. Biomaterials 32: 6111-6118 (2011). (abstract)
  • Implantation of a Tissue-engineered Heart Valve from Human Fibroblasts Exhibiting Short Term Function in the Sheep Pulmonary Artery. Syedain, Z.H., Lahti, M.T, Johnson, S.L., Robinson, P.S., Ruth, G.R., Bianco, R.W., and R.T. Tranquillo. Cardiovascular Engineering and Technology 2(2): 101-112 (2011).
  • Ruthenium-catalyzed photo cross-linking of fibrin-based engineered tissue. Bjork, J.W., Johnson, S.L., and R.T. Tranquillo. Biomaterials 32(10): 2479-2488 (2011). (abstract)
  • TGF-B1 diminishes collagen production during long-term cyclic stretching of engineered connective tissue: Implication of decreased ERK signaling
  • Syedain, Z.H. and R.T. Tranquillo
  • JBiomech 44(5): 848-55 (2011). (abstract)
  • Initial fiber alignment pattern laters extracellular matrix synthesis in fibroblast populated fibrin gel cruciforms and correlates with predicted tension. Sander, E.A., Barocas, V.H., and R.T. Tranquillo. Ann Biomed Eng (2010). (abstract)
  • Implantable arterial grafts from human fibroblasts and fibrin using a multi-graft pulsed flow-stretch bioreactor with noninvasive strength monitoring. Syedain, Z.H. Meier, L.A., Bjork, J.W, Lee, A. and R.T. Tranquilloo. Biomaterials, 32(3): 714-22 (2011). (abstract)