About

Robert T. Tranquillo is a Distinguished McKnight University Professor in the Department of Biomedical Engineering at the University of Minnesota. His research focuses on developing biologically-engineered 'off-the-shelf' vascular grafts, heart valves, and vein valves, with particular emphasis on materials produced by skin cells (fibroblasts) that have the capacity to grow, which may transform the treatment of pediatric congenital heart defects. His work involves fabricating materials from entrapped fibroblasts in fibrin gels, constraining gel compaction to create fibrin alignment, and using bioreactors to produce circumferentially-aligned tubes suitable for surgical implantation. These engineered tissues can be decellularized to become non-immunogenic, recellularize with the host, and grow, making them promising for regenerative cardiovascular applications. Additionally, his lab has created engineered human cardiac tissue containing entrapped iPSC-cardiomyocytes and a microvessel network, utilizing similar approaches. His current research includes creating transcatheter heart valves and vein valves, integrating matrix tubes with stent technology, and conferring hemocompatibility through autologous stem cell and small molecule strategies. Prof. Tranquillo's work investigates contact guidance mechanisms, cell sensing of aligned fibers, and the physical and chemical signals involved, using innovative methods such as magnetic alignment and photo-crosslinking.

Research topics

• Materials science
• Biomedical engineering
• Composite material
• Computer Science
• Biology
• Medicine
• Chromatography
• Cardiology
• Chemistry
• Optics
• Pathology
• Physics
• Cell biology
• Andrology
• Biochemistry
• Anatomy

Selected publications

• Growth of Tissue-Engineered Vascular Grafts and Heart Valves As Pediatric Conduits

  Annals of Thoracic Surgery Short Reports · 2025-11-01

  articleOpen access1st authorCorresponding

  BACKGROUND Growth is the Holy Grail of tissue implants in pediatrics, yet the outcomes from a small but increasing number of studies have not been assessed using metrics of growth.METHODS A systematic review was conducted to identify preclinical and pediatric clinical trials of implanted vascular grafts and heart valves, indicating growth of the implant based on a proposed definition of functional regenerative growth: increases in critical physical dimension(s) by increases in tissue mass with maintenance of required function. RESULTSFive distinct approaches, distinguished by scaffold type and use of preseeded cells, were identified among studies reported for tissue-engineered vascular grafts (TEVGs) and heart valves (TEHVs), with 2 of these approaches being used for both indications.A total of 11 publications were selected for data tabulation.For TEVGs, increases in length are reported across all studies (14%-130%), whereas diameter change (-38% to +89%) varied with anatomical location.For TEHVs, increases of diameter consistent with somatic growth have been reported for 4 different biologic valves (12%-78%) across preclinical studies.Commensurate leaflet growth has not been clearly established.CONCLUSIONS Growth capacity of TEVGs has been established in preclinical studies for multiple approaches, including some proceeding to clinical trials.For TEHVs, increases in the diameter are reported for several approaches in preclinical studies, but limited evidence exists to date for leaflet growth.TEVGs and TEHVs have both demonstrated potential for growth and, thus, improved clinical outcomes compared with current implants that have no growth capacity.

  PublisherOA PDFDOI

• Biologically engineered valved conduits for right ventricular outflow tract repair evaluated for 52 weeks in growing lambs

  Cardiovascular Research · 2025-03-01 · 3 citations

  articleOpen accessSenior author

  AIMS: Replacement heart valves that grow with children remain an unmet need. We previously reported valves fabricated from tubes of fibroblast-derived collagenous matrix increased in size while functioning with low systolic gradients and less than moderate regurgitation over 52 weeks in most cases, when implanted as interpositional grafts in the pulmonary artery of lambs. Here, we evaluated valved conduits fabricated by including an inflow segment to the tri-tube valve allowing for myocardial anastomosis as done in a typical right ventricular outflow tract (RVOT) surgical repair, in the same growing lamb model. METHODS AND RESULTS: In this pilot study, 19 mm valved conduits fabricated from resorbable suture were implanted into Dorset lambs (n = 3), sutured to the pulmonary annulus and distal pulmonary artery with resorbable suture after dissection of the pulmonary valve leaflets and resection of an arterial segment. Valve function and dimensions were measured with longitudinal transthoracic echocardiography. All animals exhibited an increase in valve diameter (18.2 ± 1.8 mm at 1 week to 25.1 ± 2.4 mm at 52 weeks) and leaflet free-edge length (21.1 ± 2.4 mm at 1 week to 26.2 ± 3.9 mm at 52 weeks) while functioning with at most mild regurgitation over 52 weeks. The inflow segment of the conduit grew somatically based on its unchanged thickness and increased diameter (38%) and collagen content (128%). In all three explanted conduits, the leaflets contained interstitial cells, new collagen and elastin primarily around the base, a developing endothelium on the surfaces, and they remained thin and pliable without macroscopic calcification. There was interdigitating integration of the conduit with the myocardium at the pulmonary annulus. Further, a stent was successfully placed in a valved conduit at term to evaluate feasibility of a prospective clinical intervention. CONCLUSION: This valved conduit grows in lambs based on this pilot study and thus has clinical potential for RVOT reconstruction and long-term valve growth in children.

  PublisherOA PDFDOI

• Computational construction and design optimization of a novel tri-tube heart valve

  Biomechanics and Modeling in Mechanobiology · 2025-05-26

  articleOpen accessSenior author

  A finite-element-based algorithm for the in silico construction of a novel tri-tube heart valve was developed to facilitate optimization of the leaflet geometry. An anisotropic hyperelastic model fitted to high-strain rate planar equibiaxial tension and compression data was used to approximate the nonlinear and anisotropic material behavior of biologically-engineered tubes and simulate valve closure under steady back pressure and steady forward flow. Four metrics were considered to evaluate valve performance in simulated closure: coaptation area, regurgitation area, pinwheel index, and prolapse area. Response surfaces revealed competing objectives between metrics for a valve of target 24 mm diameter in terms of two design parameters, tube diameter and leaflet height. A multi-objective genetic algorithm determined an intermediate tube diameter and leaflet height (16 mm and 11 mm, respectively) of the design space as optimal. Additionally, steady flow simulations were performed using two-way fluid-structure interaction with selected designs to examine washout behind leaflets with particle tracking. One design close to the optimal point for valve closure indicated washout for particles initially distributed behind leaflets. Though comprehensive valve design optimization requires flow analysis over multiple valve cycles to capture all effects associated with flow, this methodology based on diastolic state geometry optimization followed by steady washout analysis reduces the space of design variables for further optimization.

  PublisherOA PDFDOI

• Lab Grown Bioengineered Tissue-based Valved Conduit with Somatic Growth Potential and Framed Valve for Congenital Pulmonary Valve Disease

  Global Cardiology Science and Practice · 2025-10-06

  articleOpen accessSenior author

  Background: Congenital valve disease requires multiple interventions throughout a patient's lifetime as conventional bioprosthetic valves degrade and calcify. Current replacement options lack growth potential and lifelong durability, necessitating repeated surgeries for patients with congenital valve defect. Objective: Evaluate bioengineered lab-grown tissue heart valves utilizing two complementary approaches: (1) a fibroblast-derived collagenous matrix valved conduit with somatic growth potential for surgical implantation, and (2) a bioengineered tissue-leaflet transcatheter pulmonary valve (TPV) for minimally invasive intervention. Methods: For the valved conduit approach, 19mm conduits were implanted in growing lambs (n=3) for 52 weeks. For the TPV approach, bioengineered tissue leaflets mounted on nitinol stents were delivered via an 18Fr system and implanted in juvenile sheep (n=5) for up to 18 months. Both approaches were evaluated through serial echocardiography and histological assessment at explant. Results: The valved conduits demonstrated somatic growth with increased diameter (38%) and leaflet length (25%) while maintaining mild or less regurgitation. The TPV implants showed sustained effective orifice area (>2cm²) without increased pressure gradients (<10mmHg) or regurgitation. Both approaches exhibited favorable histology with minimal calcification and appropriate cellular infiltration. The valved conduits successfully integrated with myocardium and demonstrated feasibility of subsequent stent placement, creating a pathway for future intervention without reoperation. Conclusion: This dual-approach platform addresses immediate clinical needs through the TPV option while providing long-term solutions via the growth-accommodating valved conduit. The combined strategy offers potential for significantly reducing surgical interventions for children with congenital heart defects.

  PublisherDOI

• Evaluating Anticoagulant and Antiplatelet Therapies in Rhesus and Cynomolgus Macaques for Predictive Modeling in Humans

  Surgeries · 2024-05-17

  articleOpen access

  Anticoagulant and antiplatelet therapies are used to prevent life-threatening complications associated with thrombosis. While there are numerous clinical guidelines for antithrombotic medications, there is an incomplete understanding of whether these interventions yield similar effects in preclinical models, potentially impacting their predictive value for translational studies on the development of medical devices, therapies, and surgical techniques. Due to their close physiologic similarities to humans, we employed nonhuman primates (NHPs) using a reverse translational approach to analyze the response to clinical regimens of unfractionated heparin, low-molecular-weight heparin (LMWH) and aspirin to assess concordance with typical human responses and evaluate the predictive validity of this model. We evaluate activated clotting time (ACT) in nine rhesus and six cynomolgus macaques following the intraoperative administration of intravenous unfractionated heparin (100–300 U/kg) reflecting the clinical dose range. We observed a significant dose-dependent effect of heparin on ACT (low-dose average = 114.1 s; high-dose average = 148.3 s; p = 0.0011). LMWH and aspirin, common clinical antithrombotic prophylactics, were evaluated in three rhesus macaques. NHPs achieved therapeutic Anti-Xa levels (mean = 0.64 U/mL) and ARU (mean = 459) via VerifyNow, adhering to clinical guidance using 1.0 mg/kg enoxaparin and 81 mg aspirin. Clinical dosing strategies for unfractionated heparin, LMWH, and aspirin were safe and effective in NHPs, with no development of thrombosis or bleeding complications intraoperatively, postoperatively, or for prophylaxis. Our findings suggest that coagulation studies, performed as an integrative part of studies on biologics, bioengineered devices, or transplantation in NHPs, can be extrapolated to the clinical situation with high predictive validity.

  PublisherOA PDFDOI

• Evaluation of an engineered vascular graft exhibiting somatic growth in lambs to model repair of absent pulmonary artery branch

  Communications Medicine · 2024-10-16 · 5 citations

  articleOpen accessSenior author

  Growth is the holy grail of tissue implants in pediatrics. No vascular graft currently in use for surgical repairs of congenital heart defects has somatic growth capacity. Biologically-engineered grafts (6 mm) grown from donor ovine fibroblasts in a sacrificial fibrin gel were implanted into the left pulmonary branch of 3-month old lambs for 3, 6, and 18 months. A control group of Propaten® PTFE grafts was implanted for 6 months. The engineered grafts exhibit extensive site-appropriate recellularization after only 3 months and near-normal increase of diameter from the preimplant value of 6 mm to 12.9 mm and also a doubling of length from 6.0 mm to 13.0 mm at 6 months (n = 3) associated with apparent somatic graft growth (collagen content increase of 265% over 18-month, n = 2), along with excellent hemodynamics and no calcification, in contrast to the Propaten® grafts. The left-right flow distribution is nearly 50–50 for the engineered grafts at 6 months (n = 3) compared to about 20–80 for the Propaten® grafts (n = 3), which have less than one-half the diameter, a 6-fold higher pressure gradient, and stunted vascular development downstream of the graft. The engineered grafts exhibit a stable diameter over months 12–18 when the lambs become adult sheep (n = 2). This study supports the use of these regenerative grafts with somatic growth capacity for clinical trial in patients born with a unilateral absent pulmonary artery branch, and it shows their potential for improving development of the downstream pulmonary vasculature. Blood vessel implants that are currently used to repair heart defects at birth do not grow with the child. This means that children need to have multiple open heart surgeries to replace implants with larger implants as they grow. We grew implants from a donor sheep’s skin cells, and then completely removed the cells from the graft. We then implanted the grafts in 3-month old lambs. The lambs’ cells repopulated the implants and the implants increased in size as the lambs grew. Further experiments are required first, but our preliminary findings suggest that using a similar implant in children could improve the quality of life of children with heart defects by avoiding the need for them to have multiple surgeries to replace implants as the child grows. Syedain et al. evaluate growth of biologically-engineered grafts grown from donor ovine fibroblasts in a sacrificial fibrin gel implanted into the left pulmonary branch of 3-month old lambs. The grafts exhibit extensive site-appropriate recellularization and increase in diameter and length until the lambs reach adulthood.

  PublisherOA PDFDOI

• Challenges in the Development and Evaluation of Pediatric Heart Valve Technologies

  The Annals of Thoracic Surgery · 2024-12-16 · 2 citations

  review
  PublisherDOI

• A Career Journey in Cardiovascular Tissue Engineering

  IEEE Pulse · 2024-11-01

  article1st authorCorresponding

  A career that spans the 37 years since "tissue engineering" was coined is chronicled, including selected research and translation highlights of the author in cardiovascular applications.

  PublisherDOI

• Tissue-Engineered Heart Valves

  2023-01-01 · 5 citations

  book-chapterSenior author
  PublisherDOI

• Elucidating the signal for contact guidance contained in aligned fibrils with a microstructural–mechanical model

  Journal of The Royal Society Interface · 2022-05-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  Despite its importance in physiological processes and tissue engineering, the mechanism underlying cell contact guidance in an aligned fibrillar network has defied elucidation due to multiple interdependent signals that such a network presents to cells, namely, anisotropy of adhesion, porosity and mechanical behaviour. A microstructural-mechanical model of fibril networks was used to assess the relative magnitudes of these competing signals in networks of varied alignment strength based on idealized cylindrical pseudopods projected into the aligned and orthogonal directions and computing the anisotropy of metrics chosen for adhesion, porosity and mechanical behaviour: cylinder-fibre contact area for adhesion, persistence length of pores for porosity and total force to displace fibres from the cylindrical volume as well as network stiffness experienced upon cylinder retraction for mechanical behaviour. The signals related to mechanical anisotropy are substantially higher than adhesion and porosity anisotropy, especially at stronger network alignments, although their signal to noise (S/N) values are substantially lower. The former finding is consistent with a recent report that fibroblasts can sense fibril alignment via anisotropy of network mechanical resistance, and the model reveals this can be due to either mechanical resistance to pseudopod protrusion or retraction given their signal and S/N values are similar.

  PublisherOA PDFDOI

Recent grants

• Biopolymer-guided human stem cell assembly for engineered myocardium

  NIH · $2.9M · 2011–2017

• NIH Grant R01HL060495

  NIH · $1.2M · 2004

• NIH Grant R01HL083880

  NIH · $3.9M · 2012

• NIH Grant R29GM046052

  NIH · $478k · 1996

• Completely biological tissue-engineered pulmonic valve grown in vitro from human cells for pediatric patients

  NIH · $6.2M · 2011–2024

Frequent coauthors

• Victor H. Barocas

  Twin Cities Orthopedics

  40 shared

• Zeeshan H. Syedain

  University of Minnesota

  34 shared

• Brett C. Isenberg

  Draper Laboratory

  26 shared

• Chrysanthi Williams

  21 shared

• Michael R. Neidert

  Medtronic (United States)

  20 shared

• Sandra L. Johnson

  University of Minnesota

  17 shared

• Theodore R. Oegema

  15 shared

• J. D. Murray

  African Studies Centre

  12 shared

Labs

• Tissue Mechanics LaboratoryPI

Awards & honors

• TERMIS-AM Senior Scientist Award (2015)
• Fellow of the American Institute of Medical and Biological E…
• Fellow of the International Academy of Medical and Biologica…
• Fellow of the Biomedical Engineering Society
• Distinguished McKnight University Professor