Research Overview

Note: Prof. Tranquillo is no longer accepting new PhD students as primary adviser.

The Tranquillo Research Group is developing biologically-engineered “off-the-shelf” vascular grafts, heart valves, and vein valves. What is particularly exciting is that we have shown our material, produced by skin cells (fibroblasts), has the capacity to grow (Nature Comms, 2016) and may thus transform the treatment of pediatric congenital heart defects.

The material is fabricated from entrapping fibroblasts in a biopolymer (fibrin) gel and constraining the cell-mediated gel compaction to create fibrin alignment. Bioreactors are used to create circumferentially-aligned tubes by stimulating the cells to replace the aligned fibrin with an aligned collagenous matrix, and these tubes can then be used as vascular grafts and tubular heart valves for surgical implantation. Upon decellularization, they become “off-the-shelf” non-immunogenic vessel and valve replacements that are conducive to recellularization by the host, leading to their growth capacity. Engineered human cardiac tissue that beats via entrapped iPSC-cardiomyocytes and contains a co-aligned self-assembled microvessel network has also been created in our lab using the same approach.

Our current research focuses creating transcatheter heart valves and vein valves, combining our unique tubes of cell-produced matrix with stent technology by growing the matrix tube directly on the stent, and conferring immediate or rapid hemocompatibility of the matrix using autologous stem cell and small molecule strategies.

Contact guidance — the ability of cells to sense and aligned with aligned fibers — is crucial to our ability to create tissues with prescribed alignment, such as the circumferentially-aligned tubes. The signal presented by aligned fibrils that cells actually sense is a longstanding open question being investigated using unique methods, including magnetic alignment and photo-crosslinking of fibrin, to systematically vary the chemical/physical signals that cells might be sensing.

Education

• BS, Chemical Engineering, Pennsylvania State University, 1979
• MS, Chemical Engineering, Stanford University, 1980
• PhD, Chemical Engineering, University of Pennsylvania, 1986
• Postdoctoral Fellow, Mathematical Biology, Oxford University, 1987

Professional Background

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 served as the head of the Department of Biomedical Engineering from its inception in 2000 until 2019.  

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 120 peer-reviewed original research publications as first or senior author, being recognized with his selection for the TERMIS-AM Senior Scientist Award in 2015.

Resulting intellectual property for a regenerative cardiovascular material platform technology was licensed by Vascudyne, Inc in 2017.  

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.

Curriculum vitae

Selected Publications

Bersie-Larson, L.M., Lai, V.K., Dhume, R.Y., Provenzano, P.P., Barocas, V.H. and R. T. Tranquillo, Elucidating the signal for contact guidance contained in aligned fibrils with a microstructural-mechanical model. J Royal Soc Interface (2022)

Thrivikraman, G., et al., Cell contact guidance via sensing anisotropy of network mechanical resistance. PNAS 118: (2021)

Syedain, Z.H., et al., Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs. Sci Transl Med 13:585 (2021).

Syedain, Z., et al., Evaluation of probe burst test as a measure of strength for a biologically-engineered vascular graft.  J Mech Behav Biomed Mater 119:104527 (2021).

Thrivikraman, G., Johnson, S.L., Syedain, Z.H., Lee, H-S and R. T. Tranquillo, “Biologically-engineered mechanical model of a calcified artery,” Acta Biomaterilia 110: 164-174 (2020).

Tissue-engineered transcatheter vein valve
Syedain, Z.H., Jenson, A., Patel, P., Feagler, C., Bahmer, L., Faizer, R. and R. T. Tranquillo
Biomaterials 216: 119229 (2019).

Shear conditioning of adipose stem cells for reduced platelet binding to engineered vascular grafts
La, A. and R.T. Tranquillo
Tissue Eng Part A 24(15-16):1242-1250 (2018). (abstract)

A cardiac patch from aligned microvessel and cardiomyocyte patches
Schaefer, J.A., Guzman, P.A., Riemenschneider, S.B., Kamp, T.J. and R.T. Tranquillo
J Tissue Eng Regen Med 12:546-566 (2018). (abstract)

Implantation of a tissue-engineered tubular heart valve in growing lambs
Reimer, J.M., Syedain, Z.H., Haynie, B., Lahti, M., Berry, J. and R. T. Tranquillo 
Ann Biomed Eng 5: 439-451 (2017). (abstract)

A completely biological ‘off-the-shelf’ arteriovenous graft that  recellularizes in baboons
Syedain, Z.H., Graham, M.L., Dunn, T.B., O’Brien, T., Johnson, S.L., Schumacher, R.J. and R. T. Tranquillo
Science Transl Med 9(414):10.1126/scitranslmed.aan4209 (2017). (abstract)

Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs
Syedain, Z.H., Reimer, J. M., Lahti, M., Berry, J., Johnson, S., and R.T. Tranquillo 
Nat Commun 7:12951 (2016). (abstract)

Inosculation and perfusion of pre-vascularized tissue patches containing aligned human microvessels after myocardial infarction
Riemenschneider, S.B., Mattia, D.J., Wendel, J.S., Schaefer, J.A., Ye, L., Guzman, P.A., and R.T. Tranquillo
Biomaterials 97:51-61 (2016). (abstract)

Cyclic stretch and perfusion bioreactor for conditioning large diameter engineered tissue tubes
Schmidt, J.B. and R.T. Tranquillo
Ann Biomed Eng 44(5):1785-97 (2016). (abstract)

Tissue contraction force microscopy for optimization of engineered cardiac tissue
Schaefer, J.A. and R.T. Tranquillo
Tissue Eng Part C 22:76-83 (2016). (abstract)

6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep
Syedain, Z.H., Reimer, J.M., Schmidt, J.B., Lahti, M., Berry, J., Bianco, R. and R.T. Tranquillo
Biomaterials 73:175-84 (2015). (abstract)

Functional effects 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 4:1324-32 (2015). (abstract)

Effects of intermittent and incremental cyclic stretch on ERK signaling and collagen production in engineered tissue
Schmidt, J.B. and R.T. Tranquillo
Cell Molec Bioeng 9:55-64 (2015). (abstract)

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 bioartificial 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. Tranquillo
Biomaterials, 32(3): 714-22 (2011). (abstract)