All Publications


  • Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth. Communications medicine Blum, K. M., Zbinden, J. C., Ramachandra, A. B., Lindsey, S. E., Szafron, J. M., Reinhardt, J. W., Heitkemper, M., Best, C. A., Mirhaidari, G. J., Chang, Y., Ulziibayar, A., Kelly, J., Shah, K. V., Drews, J. D., Zakko, J., Miyamoto, S., Matsuzaki, Y., Iwaki, R., Ahmad, H., Daulton, R., Musgrave, D., Wiet, M. G., Heuer, E., Lawson, E., Schwarz, E., McDermott, M. R., Krishnamurthy, R., Krishnamurthy, R., Hor, K., Armstrong, A. K., Boe, B. A., Berman, D. P., Trask, A. J., Humphrey, J. D., Marsden, A. L., Shinoka, T., Breuer, C. K. 2022; 2: 3

    Abstract

    Background: Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity.Methods: Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models.Results: Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid-structure interaction simulations providing detailed hemodynamic and wall stress information.Conclusions: These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease.

    View details for DOI 10.1038/s43856-021-00063-7

    View details for PubMedID 35603301

  • Patient-specific changes in aortic hemodynamics is associated with thrombotic risk after fenestrated endovascular aneurysm repair with large diameter endografts. JVS-vascular science Tran, K., Feliciano, K. B., Yang, W., Schwarz, E. L., Marsden, A. L., Dalman, R. L., Lee, J. T. 2022; 3: 219-231

    Abstract

    Background: The durability of fenestrated endovascular aneurysm repair (fEVAR) has been threatened by thrombotic complications. In the present study, we used patient-specific computational fluid dynamic (CFD) simulation to investigate the effect of the endograft diameter on hemodynamics after fEVAR and explore the hypothesis that diameter-dependent alterations in aortic hemodynamics can predict for thrombotic events.Methods: A single-institutional retrospective study was performed of patients who had undergone fEVAR for juxtarenal aortic aneurysms. The patients were stratified into large diameter (34-36mm) and small diameter (24-26mm) endograft groups. Patient-specific CFD simulations were performed using three-dimensional paravisceral aortic models created from computed tomographic images with allometrically scaled boundary conditions. Aortic time-averaged wall shear stress (TAWSS) and residence time (RT) were computed and correlated with future thrombotic complications (eg, renal stent occlusion, development of significant intraluminal graft thrombus).Results: A total of 36 patients (14 with a small endograft and 22 with a large endograft) were included in the present study. The patients treated with large endografts had experienced a higher incidence of thrombotic complications compared with small endografts (45.5% vs 7.1%; P= .016). Large endografts were associated with a lower postoperative aortic TAWSS (1.45± 0.76dynes/cm2 vs 3.16± 1.24dynes/cm2; P< .001) and longer aortic RT (0.78± 0.30second vs 0.34± 0.08second; P< .001). In the large endograft group, a reduction >0.39dynes/cm2 in aortic TAWSS demonstrated discriminatory power for thrombotic complications (area under the receiver operating characteristic curve, 0.77). An increased aortic RT of ≥0.05second had similar accuracy for predicting thrombotic complications (area under the receiver operating characteristic curve, 0.78). The odds of thrombotic complications were significantly higher if patients had met the hemodynamic threshold changes in aortic TAWSS (odds ratio, 7.0; 95% confidence interval, 1.1-45.9) and RT (odds ratio, 8.0; 95% confidence interval, 1.13-56.8).Conclusions: Patient-specific CFD simulation of fEVAR in juxtarenal aortic aneurysms demonstrated significant endograft diameter-dependent differences in aortic hemodynamics. A postoperative reduction in TAWSS and an increased RT correlated with future thrombotic events after large-diameter endograft implantation. Patient-specific simulation of hemodynamics provides a novel method for thrombotic risk stratification after fEVAR.

    View details for DOI 10.1016/j.jvssci.2022.04.002

    View details for PubMedID 35647564

  • Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients. NPJ Regenerative medicine Schwarz, E. L., Kelly, J. M., Blum, K. M., Hor, K. N., Yates, A. R., Zbinden, J. C., Verma, A., Lindsey, S. E., Ramachandra, A. B., Szafron, J. M., Humphrey, J. D., Shin'oka, T., Marsden, A. L., Breuer, C. K. 2021; 6 (1): 38

    Abstract

    In the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.

    View details for DOI 10.1038/s41536-021-00148-w

    View details for PubMedID 34294733