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 (fibrin) 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. Bioreactors are used to create tissue-equivalent tubes by simulating the cells to replace the aligned fibrin with an aligned collagenous matrix. Upon decellularization, they are sufficiently strong to be implanted as vascular grafts and tubular hearts valves and are conducive to recellularization by the host, leading to growth capacity. Engineered human cardiac tissue that beats via entrapped iPSC-cardiomyocytes and contains a self-assembled microvascular network has been created using the same tissue-equivalent approach.
Our current research in cardiovascular tissue engineering focuses creating transcatheter heart valves and vein valves, combining our unique tubes of cell-produced matrix with stent technology, 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 underlying mechanism of contact guidance is also 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.
- Distinguished McKnight University Professor
- Fellow of the Biomedical Engineering Society
- Fellow of the American Institute for Medical and Biological Engineering
- College Student Board Outstanding Professor in Biomedical Engineering
- Shell Land Grant Chair in Chemical Engineering & Materials Science
- NSF Presidential Young Investigator
- McKnight-Land Grant Professor
- Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs Syedain, Z.H., Reimer, J. M., Lahti, M., Berry, J., and R.T. Tranquillo Nat Comm (in press).
- 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).
- Implantation of a tissue-engineered tubular heart valve in growing lambs Reimer, J.M., Syedain, Z.H., Haynei, B., Lahti, M., Berry, J. and R.T. Tranquillo Ann Biomed Eng (accepted).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).