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Office: 7-114 Nils Hasselmo Hall
Phone: 612-625-6868
Email: tranquillo@umn.edu
B.S., Chemical Engineering, Pennsylvania State University, 1979
M.S., Chemical Engineering, Stanford University, 1980
Ph.D., Chemical Engineering, University of Pennsylvania, 1986
Postdoctoral Fellow, Mathematical Biology, Oxford University, 1987
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. Doris Taylor).
In all these projects, the use of blood-derived endothelial cells is being explored to provide a quiescent endothelium at implantation and possibly a functional microvasculature within the tissue as well (with Prof. Robert Hebbel). Also, animal studies are also being conducted (with Experimental Surgical Services).
A new direction aims to integrate “systems biology” with tissue engineering for developing a rationale approach to the use of stimuli to drive tissue growth. Cell signals are being measured in response to stimulation (mechanical or chemical) to determine the optimal stimulation regimen for maximizing outcomes of interest.
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
TissueEng Part A, 17(19-20):2511-21 (2011).
(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). (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)
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)
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 39:714 (2011). (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)
Fibrin Degradation Enhances Vascular Smooth Muscle Cell Proliferation and Matrix Deposition in Fibrin-Based Tissue Constructs Fabricated In Vitro
Ahmann, K.A., Weinbaum, J.S., Johnson, S.L., and R.T. Tranquillo
Tissue Eng Part A, 16(10): 3261-70 (2010). (abstract)
The Matrix-Binding Domain of Microfibril-associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix
Weinbaum, J.S., Tranquillo, R.T., and R.P. Mecham
Macromol Biosci, 10: 1338-44 (2010). (abstract)
Fusion of concentrically layered tubular tissue constructs increases burst strength
Huynh, T.N. and R.T. Tranquillo
Ann Biomed Eng, 38: 2226 (2010). (abstract)
Monitoring Collagen Transcription by Vascular Smooth Muscle Cells in Fibrin-Based Tissue Constructs
Weinbaum, J. S. and R. T. Tranquillo
Tissue Eng Part C , 16(3): 459-67 (2010). (abstract)
Controlled compaction with ruthenium-catalyzed photochemical cross-linking of fibrin-based engineered connective tissue
Syedain, Z.H., Bjork, J.W., Sando, L., and R.T. Tranquillo
Biomaterials, 30: 6695-701 (2009). (abstract)
Image-based multi-scale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels
Sander, E.A., Stylianopoulos, T., Tranquillo, R. T., and V. H. Barocas
PNAS 106(42): 17675-80 (2009). (abstract)
Transmural Flow Bioreactor for Vascular Tissue Engineering
Bjork, J. W. and R. T. Tranquillo
Biotech & Bioeng, 104: 1197-206 (2009). (abstract)
A Bioreactor for Tissue Engineered Heart Valves Based on Controlled Cyclic Stretching
Syedain, Z. and R. T. Tranquillo
Biomaterials, 30: 4078-84 (2009). (abstract)
Cell-induced alignment augments twitch force of fibrin gel-based engineered myocardium
Black, L.D., Meyers, J.D., Weinbaum, J.S., Shvelidze, Y.A. and R. T. Tranquillo
Tissue Eng Part A. 15: 3099-108 (2009). (abstract)
Planar Biaxial Behavior of Native and Tissue-Engineered Heart Valve Leaflets
Robinson, P.S. and R.T. Tranquillo
Tissue Eng Part A. 15: 2763-72 (2009). (abstract)
Fiber Re-Orientation in Planar Biaxial Loading of Bioartificial Tissues Possessing Prescribed Alignment
Jhun, C-S, Evas, M.C., Barocas, V.H. and R.T. Tranquillo
J Biomech Eng, 131: 081006-1-0810068 (2009 - cover photo). (abstract)
Image-Based Biomechanics of Collagen Based Tissue Equivalents: Multiscale Models Compared To Fiber Alignment Predicted by Polarimetric Imaging
Sander, E.A., Stylianopoulos, T., Tranquillo, R.T., and V.H. Barocas
IEEE Eng Med Biol, 28(3): 10-18 (2009). (abstract)
Functional Tissue-Engineered Valves from Cell-Remodeled Fibrin with Commissural Alignment of Cell-Produced Collagen
Robinson, P. S., Johnson, S. L., Evans, M. C., Barocas, V.H. and R. T. Tranquillo
Tissue Eng Part A. 14: 83-95 (2008). (abstract)
Cyclic Distension of Fibrin-Based Tissue Constructs: Evidence of Adaptation During Growth of Engineered Connective Tissue
Syedain, Z., Weinberg, J.S., and R. T. Tranquillo, PNAS 105:6537-6542 (2008). (abstract)
Cytokine Induction of Functional Smooth Muscle Cells from Multipotent Adult Progenitor Cells
Ross J.J., Zhigang H., Willenbring B., Zeng L., Isenberg B., Lee E.H., Reyes M., Keirstead S.A., Weir E.K., Tranquillo R.T., Verfaillie C.M.
J Clin Invest. 2006 116:3139-3149. (abstract)
Small-diameter artificial arteries engineered in vitro {Review}
Isenberg, B.C., Williams, C. and R.T. Tranquillo
Circ Res. 2006 Jan 6;98(1):25-35. (abstract)
Endothelialization and Flow Conditioning of Fibrin-based Media-equivalents
Isenberg, B.C., Williams, C. and R.T. Tranquillo
Ann Biomed Eng. 2006 Jun;34(6):971-85. (abstract)
Cell Sourcing for Fibrin-Based Valve Constructs
Williams, C., Johnson, S. L., Robinson, P. S. and R. T. Tranquillo
Tissue Eng. 2006 Jun;12(6):1489-502. (abstract)
Tissue engineered valves with commissural alignment
Neidert, M.R. and Tranquillo, R.T.
Tissue Eng. 2006 Apr;12(4):891-903. (abstract)
Schwann cell behavior in three-dimensional collagen gels: Evidence for differential mechano-transduction and the influence of TGF-beta1 in morphological polarization and differentiation
Rosner, B. I., Hang, T-C., and R. T. Tranquillo
Exp Neurol. 2005 Sep;195(1):81-91.
Cryopreservation of collagen-based tissue equivalents. II. Improved freezing in the presence of cryoprotective agents.
Neidert MR, Devireddy RV, Tranquillo RT, Bischof JC.
Tissue Eng. 2004 Jan-Feb;10(1-2):23-32.
Rational design of contact guiding, neurotrophic matrices for peripheral nerve regeneration.
Rosner BI, Siegel RA, Grosberg A, Tranquillo RT.
Ann Biomed Eng. 2003 Dec;31(11):1383-401.
Cryopreservation of collagen-based tissue equivalents. I. Effect of freezing in the absence of cryoprotective agents.
Devireddy RV, Neidert MR, Bischof JC, Tranquillo RT.
Tissue Eng. 2003 Dec;9(6):1089-100.
Elastic fiber production in cardiovascular tissue-equivalents.
Long JL, Tranquillo RT.
Matrix Biol. 2003 Jun;22(4):339-50.
Long-term cyclic distention enhances the mechanical properties of collagen-based media-equivalents.
Isenberg BC, Tranquillo RT.
Ann Biomed Eng. 2003 Sep;31(8):937-49.
A fibrin-based arterial media equivalent.
Grassl ED, Oegema TR, Tranquillo RT.
J Biomed Mater Res. 2003 Sep 1;66A(3):550-61.
Temporal variations in cell migration and traction during fibroblast-mediated gel compaction.
Shreiber DI, Barocas VH, Tranquillo RT.
Biophys J. 2003 Jun;84(6):4102-14.
Fiber alignment imaging during mechanical testing of soft tissues.
Tower TT, Neidert MR, Tranquillo RT.
Ann Biomed Eng. 2002 Nov-Dec;30(10):1221-33.
Confined compression of a tissue-equivalent: collagen fibril and cell alignment in response to anisotropic strain.
Girton TS, Barocas VH, Tranquillo RT.
J Biomech Eng. 2002 Oct;124(5):568-75.
A novel implantable collagen gel assay for fibroblast traction and proliferation during wound healing.
Enever PA, Shreiber DI, Tranquillo RT.
J Surg Res. 2002 Jun 15;105(2):160-72.
Enhanced fibrin remodeling in vitro with TGF-beta1, insulin and plasmin for improved tissue-equivalents.
Neidert MR, Lee ES, Oegema TR, Tranquillo RT.
Biomaterials. 2002 Sep;23(17):3717-31.
The tissue-engineered small-diameter artery.
Tranquillo RT.
Ann N Y Acad Sci. 2002 Jun;961:251-4.
Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay.
Bromberek BA, Enever PA, Shreiber DI, Caldwell MD, Tranquillo RT.
Exp Cell Res. 2002 May 1;275(2):230-42.
Fibrin as an alternative biopolymer to type-I collagen for the fabrication of a media equivalent.
Grassl ED, Oegema TR, Tranquillo RT.
J Biomed Mater Res. 2002 Jun 15;60(4):607-12.
Alignment maps of tissues: II. Fast harmonic analysis for imaging.
Tower TT, Tranquillo RT.
Biophys J. 2001 Nov;81(5):2964-71.
Alignment maps of tissues: I. Microscopic elliptical polarimetry.
Tower TT, Tranquillo RT.
Biophys J. 2001 Nov;81(5):2954-63.
Neuronal contact guidance in magnetically aligned fibrin gels: effect of variation in gel mechano-structural properties.
Dubey N, Letourneau PC, Tranquillo RT.
Biomaterials. 2001 May;22(10):1065-75.
Effects of pdgf-bb on rat dermal fibroblast behavior in mechanically stressed and unstressed collagen and fibrin gels.
Shreiber DI, Enever PA, Tranquillo RT.
Exp Cell Res. 2001 May 15;266(1):155-66.
A self-consistent cell flux expression for simultaneous chemotaxis and contact guidance in tissues.
Wagle MA, Tranquillo RT.
J Math Biol. 2000 Oct;41(4):315-30.
Mechanisms of stiffening and strengthening in media-equivalents fabricated using glycation.
Girton TS, Oegema TR, Grassl ED, Isenberg BC, Tranquillo RT.
J Biomech Eng. 2000 Jun;122(3):216-23.
Guided neurite elongation and schwann cell invasion into magnetically aligned collagen in simulated peripheral nerve regeneration.
Dubey N, Letourneau PC, Tranquillo RT.
Exp Neurol. 1999 Aug;158(2):338-50.
Magnetically aligned collagen gel filling a collagen nerve guide improves peripheral nerve regeneration.
Ceballos D, Navarro X, Dubey N, Wendelschafer-Crabb G, Kennedy WR, Tranquillo RT.
Exp Neurol. 1999 Aug;158(2):290-300.
Exploiting glycation to stiffen and strengthen tissue equivalents for tissue engineering.
Girton TS, Oegema TR, Tranquillo RT.
J Biomed Mater Res. 1999 Jul;46(1):87-92.
Self-organization of tissue-equivalents: the nature and role of contact guidance.
Tranquillo RT.
Biochem Soc Symp. 1999;65:27-42.
A fibrin or collagen gel assay for tissue cell chemotaxis: assessment of fibroblast chemotaxis to GRGDSP.
Knapp DM, Helou EF, Tranquillo RT.
Exp Cell Res. 1999 Mar 15;247(2):543-53.
Engineered alignment in media equivalents: magnetic prealignment and mandrel compaction.
Barocas VH, Girton TS, Tranquillo RT.
J Biomech Eng. 1998 Oct;120(5):660-6.
A finite element solution for the anisotropic biphasic theory of tissue-equivalent mechanics: the effect of contact guidance on isometric cell traction measurement.
Barocas VH, Tranquillo RT.
J Biomech Eng. 1997 Aug;119(3):261-8.
An anisotropic biphasic theory of tissue-equivalent mechanics: the interplay among cell traction, fibrillar network deformation, fibril alignment, and cell contact guidance.
Barocas VH, Tranquillo RT.
J Biomech Eng. 1997 May;119(2):137-45.
Magnetically orientated tissue-equivalent tubes: application to a circumferentially orientated media-equivalent.
Tranquillo RT, Girton TS, Bromberek BA, Triebes TG, Mooradian DL.
Biomaterials. 1996 Feb;17(3):349-57.
Stochastic model of receptor-mediated cytomechanics and dynamic morphology of leukocytes.
Tranquillo RT, Alt W.
J Math Biol. 1996;34(4):361-412.
The fibroblast-populated collagen microsphere assay of cell traction force--Part 2: Measeurement of the cell traction parameter.
Barocas VH, Moon AG, Tranquillo RT.
J Biomech Eng. 1995 May;117(2):161-70