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Christopher K. Breuer - One of the best experts on this subject based on the ideXlab platform.
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targeted imaging of matrix metalloproteinase activity in the evaluation of remodeling tissue engineered vascular grafts implanted in a growing lamb model
The Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Mitchel R Stacy, Yuji Naito, Toshiharu Shinoka, Mark W Maxfield, Hirotsugu Kurobe, Shuhei Tara, Chung Chan, Kevin A Rocco, Albert J Sinusas, Christopher K. BreuerAbstract:Objectives The clinical translation of tissue-engineered vascular grafts has been demonstrated in children. The remodeling of biodegradable, cell-seeded scaffolds to functional Neovessels has been partially attributed to matrix metalloproteinases. Noninvasive assessment of matrix metalloproteinase activity can indicate graft remodeling and elucidate the progression of neovessel formation. Therefore, matrix metalloproteinase activity was evaluated in grafts implanted in lambs using in vivo and ex vivo hybrid imaging. Graft growth and remodeling was quantified using in vivo x-ray computed tomography angiography. Methods Cell-seeded and unseeded scaffolds were implanted in 5 lambs as inferior vena cava interposition grafts. At 2 and 6 months after implantation, in vivo angiography was used to assess graft morphology. In vivo and ex vivo single photon emission tomography/computed tomography imaging was performed with a radiolabeled compound targeting matrix metalloproteinase activity at 6 months. The neotissue was examined at 6 months using qualitative histologic and immunohistochemical staining and quantitative biochemical analysis. Results The seeded grafts demonstrated significant luminal and longitudinal growth from 2 to 6 months. In vivo imaging revealed subjectively greater matrix metalloproteinase activity in grafts versus native tissue. Ex vivo imaging confirmed a quantitative increase in matrix metalloproteinase activity and demonstrated greater activity in unseeded versus seeded grafts. The glycosaminoglycan content was increased in seeded grafts versus unseeded grafts, without significant differences in collagen content. Conclusions Matrix metalloproteinase activity remained elevated in tissue-engineered grafts 6 months after implantation and could indicate remodeling. Optimization of in vivo imaging to noninvasively evaluate matrix metalloproteinase activity could assist in the serial assessment of vascular graft remodeling.
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Abstract 233: Quantification of Histological and Biomechanical Properties of Tissue-Engineered Vascular Graft in Inferior Vena Cava
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Yuji Naito, Yong-ung Lee, Spencer N. Church, Daniel A. Solomon, Jay D. Humphrey, Toshiharu Shinoka, Christopher K. BreuerAbstract:Background: We developed the first tissue engineered vascular graft (TEVG) for use in congenital heart surgery and confirmed its significant potential via an initial clinical trial (Shinoka et al., JTCVS 2005). The primary complication of TEVG at medium term was stenosis attributed to suboptimal neovessel remodeling, which necessitated an investigation of the mechanics and mechanobiology to predict diverse aspects of the neovessel formation. Here we present the novel tools to investigate the evolving biomechanical properties of TEVG in a mouse inferior vena cava (IVC) replacement model. Hypothesis: The biomechanical properties of a TEVG evolve nonlinearly in time from a construct-dominated stiffness to a neovessel dominated stiffness. Novel biaxial biomechanical tests are required to quantify such changes rigorously. Method: Thirty-six CB17 SCID/beige mice were implanted with TEVG (PGA + P[CL/LA]) as IVC interposition graft. Twelve tissue engineered Neovessels were harvested at 2, 6, and 12 weeks after implantation. Neovessels were characterized biomechanically using a custom, computer-controlled biaxial testing device, and compared with native veins. Extracellular matrix (ECM) remodeling of the neovessel was characterized histologically, biochemically, and molecular biologically. Result: The biaxial data revealed an improved compliance of the neovessel over time. Similarly, the axial stretch response of the TEVG became more like the native vein at 12 weeks. This response was quantified as a ratio of neo-vessel to native vein and improved to reach 52% at 12 weeks from 11% at 2 weeks. Scaffold mass in vivo, estimated by remaining scaffold on histology, showed a significant decline at 6 and 12 weeks. Gene expression of both type I and III collagen peaked at 2 weeks, and total collagen mass quantified by a Sircol™ assay revealed that total collagen peaked at 2 weeks but decreased gradually to the level of native vein. Gene expression of both tropoelastin and fibrillin-1 peaked at 2 weeks, whereas elastin mass quantified by Fastin™ assay showed a delayed peak level of elastin at 6 weeks. Gene expression of MMP-2 and 9 peaked at 6 and 2 weeks, respectively, implicating robust ECM remodeling at early time points. Conclusion: Our novel histo-mechanical approach is the first to show that neovessel formation is a dynamic process characterized by progressive degradation of the scaffold and increased ECM remodeling, which yields biomechanical properties of the TEVG similar to native vessel within 12 weeks in vivo.
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tissue engineered arterial grafts long term results after implantation in a small animal model
Journal of Pediatric Surgery, 2009Co-Authors: Tamar L Mirensky, Toshiharu Shinoka, Narutoshi Hibino, Matthew P Brennan, Gregory N Nelson, Tai Yi, Christopher K. BreuerAbstract:Abstract Background Use of prosthetic vascular grafts in pediatric vascular surgical applications is limited because of risk of infection, poor durability, potential for thromboembolic complications, and lack of growth potential. Construction of an autologous neovessel using tissue engineering technology offers the potential to create an improved vascular conduit for use in pediatric vascular applications. Methods Tissue-engineered vascular grafts were assembled from biodegradable tubular scaffolds fabricated from poly-l-lactic acid mesh coated with ɛ -caprolactone and l-lactide copolymer. Thirteen scaffolds were seeded with human aortic endothelial and smooth muscle cells and implanted as infrarenal aortic interposition grafts in SCID/bg mice. Grafts were analyzed at time-points ranging from 4 days to 1 year after implantation. Results All grafts remained patent without evidence of thromboembolic complications, graft stenosis, or graft rupture as documented by serial ultrasound and computed tomographic angiogram, and confirmed histologically. All grafts demonstrated extensive remodeling leading to the development of well-circumscribed Neovessels with an endothelial inner lining, neomedia containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. Conclusions The development of second-generation tissue-engineered vascular grafts shows marked improvement over previous grafts and confirms feasibility of using tissue engineering technology to create an improved arterial conduit for use in pediatric vascular surgical applications.
Narutoshi Hibino - One of the best experts on this subject based on the ideXlab platform.
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tissue engineered vascular grafts form Neovessels that arise from regeneration of the adjacent blood vessel
The FASEB Journal, 2011Co-Authors: Narutoshi Hibino, Gustavo A Villalona, Nicholas Pietris, Daniel R Duncan, Adam Schoffner, Jason D Roh, Lawrence W Dobrucki, Dane Mejias, Rajendra Sawhmartinez, Jamie K HarringtonAbstract:We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin. Here, we investigate the source of neotissue cells in syngeneic BMMC-seeded grafts, implanted into immunocompetent mouse recipients. We again find that seeded BMMCs are lost, declining to 0.02% at 14 d, concomitant with host macrophage invasion. In addition, we demonstrate using sex-mismatched chimeric hosts that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel. Furthermore, using composite grafts formed from seeded scaffold anastomosed to sex-mismatched natural vessel segments, we demonstrate that the adjacent vessel wall is the principal source of these endothelial and smooth muscle cells, forming 93% of proximal neotissue. These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body's innate healing capabilities to “regenerate” neotissue from preexisting committed tissue cells.—Hibino, N., Villalona, G., Pietris, N., Duncan, D. R., Schoffner, A., Roh, J. D., Yi, T., Dobrucki, L. W., Mejias, D., Sawh-Martinez, R., Harrington, J. K., Sinusas, A., Krause, D. S., Kyriakides, T., Saltzman, W. M., Pober, J. S., Shin'oka, T., Breuer, C. K. Tissue-engineered vascular grafts form Neovessels that arise from regeneration of the adjacent blood vessel.
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tissue engineered vascular grafts transform into mature blood vessels via an inflammation mediated process of vascular remodeling
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Jason D Roh, Rajendra Sawhmartinez, Matthew P Brennan, Steven M Jay, Lesley Devine, Deepak A Rao, Tamar L Mirensky, Ani Nalbandian, Brooks V Udelsman, Narutoshi HibinoAbstract:Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional Neovessels via an inflammatory process of vascular remodeling.
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tissue engineered arterial grafts long term results after implantation in a small animal model
Journal of Pediatric Surgery, 2009Co-Authors: Tamar L Mirensky, Toshiharu Shinoka, Narutoshi Hibino, Matthew P Brennan, Gregory N Nelson, Tai Yi, Christopher K. BreuerAbstract:Abstract Background Use of prosthetic vascular grafts in pediatric vascular surgical applications is limited because of risk of infection, poor durability, potential for thromboembolic complications, and lack of growth potential. Construction of an autologous neovessel using tissue engineering technology offers the potential to create an improved vascular conduit for use in pediatric vascular applications. Methods Tissue-engineered vascular grafts were assembled from biodegradable tubular scaffolds fabricated from poly-l-lactic acid mesh coated with ɛ -caprolactone and l-lactide copolymer. Thirteen scaffolds were seeded with human aortic endothelial and smooth muscle cells and implanted as infrarenal aortic interposition grafts in SCID/bg mice. Grafts were analyzed at time-points ranging from 4 days to 1 year after implantation. Results All grafts remained patent without evidence of thromboembolic complications, graft stenosis, or graft rupture as documented by serial ultrasound and computed tomographic angiogram, and confirmed histologically. All grafts demonstrated extensive remodeling leading to the development of well-circumscribed Neovessels with an endothelial inner lining, neomedia containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. Conclusions The development of second-generation tissue-engineered vascular grafts shows marked improvement over previous grafts and confirms feasibility of using tissue engineering technology to create an improved arterial conduit for use in pediatric vascular surgical applications.
Jeffrey A. Weiss - One of the best experts on this subject based on the ideXlab platform.
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Stromal Cells Promote Neovascular Invasion Across Tissue Interfaces.
Frontiers in physiology, 2020Co-Authors: Hannah A. Strobel, Laxminarayanan Krishnan, Steven A. Labelle, Jacob R. Dale, Adam Rauff, A. Marsh Poulson, Nathan Bader, Jason E. Beare, Klevis Aliaj, Jeffrey A. WeissAbstract:Vascular connectivity between adjacent vessel beds within and between tissue compartments is essential to any successful neovascularization process. To establish new connections, growing Neovessels must locate other vascular elements during angiogenesis, often crossing matrix and other tissue-associated boundaries and interfaces. How growing Neovessels traverse any tissue interface, whether part of the native tissue structure or secondary to a regenerative procedure (e.g., an implant), is not known. In this study, we developed an experimental model of angiogenesis wherein growing Neovessels must interact with a 3D interstitial collagen matrix interface that separates two distinct tissue compartments. Using this model, we determined that matrix interfaces act as a barrier to neovessel growth, deflecting growing Neovessels parallel to the interface. Computational modeling of the neovessel/matrix biomechanical interactions at the interface demonstrated that differences in collagen fibril density near and at the interface are the likely mechanism of deflection, while fibril alignment guides deflected Neovessels along the interface. Interestingly, stromal cells facilitated neovessel interface crossing during angiogenesis via a vascular endothelial growth factor (VEGF)-A dependent process. However, ubiquitous addition of VEGF-A in the absence of stromal cells did not promote interface invasion. Therefore, our findings demonstrate that vascularization of a tissue via angiogenesis involves stromal cells providing positional cues to the growing neovasculature and provides insight into how a microvasculature is organized within a tissue.
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Large-scale time series microscopy of neovessel growth during angiogenesis
Angiogenesis, 2015Co-Authors: Urs Utzinger, Brenda Baggett, Jeffrey A. Weiss, James B. Hoying, Lowell T. EdgarAbstract:During angiogenesis, growing Neovessels must effectively navigate through the tissue space as they elongate and subsequently integrate into a microvascular network. While time series microscopy has provided insight into the cell activities within single growing neovessel sprouts, less is known concerning neovascular dynamics within a large angiogenic tissue bed. Here, we developed a time-lapse imaging technique that allowed visualization and quantification of sprouting Neovessels as they form and grow away from adult parent microvessels in three dimensions over cubic millimeters of matrix volume during the course of up to 5 days on the microscope. Using a new image acquisition procedure and novel morphometric analysis tools, we quantified the elongation dynamics of growing Neovessels and found an episodic growth pattern accompanied by fluctuations in neovessel diameter. Average elongation rate was 5 μm/h for individual vessels, but we also observed considerable dynamic variability in growth character including retraction and complete regression of entire Neovessels. We observed neovessel-to-neovessel directed growth over tens to hundreds of microns preceding tip-to-tip inosculation. As we have previously described via static 3D imaging at discrete time points, we identified different collagen fibril structures associated with the growing neovessel tip and stalk, and observed the coordinated alignment of growing Neovessels in a deforming matrix. Overall analysis of the entire image volumes demonstrated that although individual Neovessels exhibited episodic growth and regression, there was a monotonic increase in parameters associated with the entire vascular bed such as total network length and number of branch points. This new time-lapse imaging approach corroborated morphometric changes in individual Neovessels described by us and others, as well as captured dynamic neovessel behaviors unique to days-long angiogenesis within the forming neovascular network.
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A coupled model of neovessel growth and matrix mechanics describes and predicts angiogenesis in vitro.
Biomechanics and modeling in mechanobiology, 2014Co-Authors: Lowell T. Edgar, Steve A. Maas, James E. Guilkey, Jeffrey A. WeissAbstract:During angiogenesis, sprouting microvessels interact with the extracellular matrix (ECM) by degrading and reorganizing the matrix, applying traction forces, and producing deformation. Morphometric features of the resulting microvascular network are affected by the interaction between the matrix and angiogenic microvessels. The objective of this study was to develop a continuous–discrete modeling approach to simulate mechanical interactions between growing Neovessels and the deformation of the matrix in vitro. This was accomplished by coupling an existing angiogenesis growth model which uses properties of the ECM to regulate angiogenic growth with the nonlinear finite element software FEBio (www.febio.org). FEBio solves for the deformation and remodeling of the matrix caused by active stress generated by neovessel sprouts, and this deformation was used to update the ECM into the current configuration. After mesh resolution and parameter sensitivity studies, the model was used to accurately predict vascular alignment for various matrix boundary conditions. Alignment primarily arises passively as microvessels convect with the deformation of the matrix, but active alignment along collagen fibrils plays a role as well. Predictions of alignment were most sensitive to the range over which active stresses were applied and the viscoelastic time constant in the material model. The computational framework provides a flexible platform for interpreting in vitro investigations of vessel–matrix interactions, predicting new experiments, and simulating conditions that are outside current experimental capabilities.
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Formation of Microvascular Networks: Role of Stromal Interactions Directing Angiogenic Growth
Microcirculation (New York N.Y. : 1994), 2014Co-Authors: James B. Hoying, Urs Utzinger, Jeffrey A. WeissAbstract:In the adult, angiogenesis leads to an expanded microvascular network as new vessel segments are added to an existing microcirculation. Necessarily, growing Neovessels must navigate through tissue stroma as they locate and grow toward other vessel elements. We have a growing body of evidence demonstrating that angiogenic Neovessels reciprocally interact with the interstitial matrix of the stroma resulting in directed neovascular growth during angiogenesis. Given the compliance and the viscoelastic properties of collagen, neovessel guidance by the stroma is likely due to compressive strain transverse to the direction of primary tensile forces present during active tissue deformation. Similar stromal strains control the final network topology of the new microcirculation, including the distribution of arterioles, capillaries, and venules. In this case, stromal-derived stimuli must be present during the post-angiogenesis remodeling and maturation phases of neovascularization to have this effect. Interestingly, the preexisting organization of vessels prior to the start of angiogenesis has no lasting influence on the final, new network architecture. Combined, the evidence describes interplay between angiogenic Neovessels and stroma that is important in directed neovessel growth and invasion. This dynamic is also likely a mechanism by which global tissue forces influence vascular form and function.
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Mechanical Interaction of Angiogenic Microvessels With the Extracellular Matrix
Journal of biomechanical engineering, 2014Co-Authors: Lowell T. Edgar, Urs Utzinger, Brenda Baggett, James B. Hoying, Laxminarayanan Krishnan, Clayton J. Underwood, Steve A. Maas, James E. Guilkey, Jeffrey A. WeissAbstract:Angiogenesis is the process by which new blood vessels sprout from existing blood vessels, enabling new vascular elements to be added to an existing vasculature. This review discusses our investigations into the role of cell-matrix mechanics in the mechanical regulation of angiogenesis. The experimental aspects of the research are based on in vitro experiments using an organ culture model of sprouting angiogenesis with the goal of developing new treatments and techniques to either promote or inhibit angiogenic outgrowth, depending on the application. Computational simulations were performed to simulate angiogenic growth coupled to matrix deformation, and live two-photon microscopy was used to obtain insight into the dynamic mechanical interaction between angiogenic Neovessels and the extracellular matrix. In these studies, we characterized how angiogenic Neovessels remodel the extracellular matrix (ECM) and how properties of the matrix such as density and boundary conditions influence vascular growth and alignment. Angiogenic Neovessels extensively deform and remodel the matrix through a combination of applied traction, proteolytic activity, and generation of new cell-matrix adhesions. The angiogenic phenotype within endothelial cells is promoted by ECM deformation and remodeling. Sensitivity analysis using our finite element model of angiogenesis suggests that cell-generated traction during growth is the most important parameter controlling the deformation of the matrix and, therefore, angiogenic growth and remodeling. Live two-photon imaging has also revealed numerous neovessel behaviors during angiogenesis that are poorly understood such as episodic growth/regression, neovessel colocation, and anastomosis. Our research demonstrates that the topology of a resulting vascular network can be manipulated directly by modifying the mechanical interaction between angiogenic Neovessels and the matrix.
Innocente Figini - One of the best experts on this subject based on the ideXlab platform.
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Sickle cell-hemoglobin C retinopathy: transient obstruction of retinal and choroidal circulations and transient drying out of retinal Neovessels
International Ophthalmology, 2008Co-Authors: Alessandro Mantovani, Innocente FiginiAbstract:We present a case of sickle cell-hemoglobin C disease that presented acute retinal and choroidal peripheral non-perfusion on the base of chronic microvascular obstruction, which transiently closed retinal Neovessels.
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Sickle cell-hemoglobin C retinopathy: transient obstruction of retinal and choroidal circulations and transient drying out of retinal Neovessels
International Ophthalmology, 2008Co-Authors: Alessandro Mantovani, Innocente FiginiAbstract:We present a case of sickle cell-hemoglobin C disease that presented acute retinal and choroidal peripheral non-perfusion on the base of chronic microvascular obstruction, which transiently closed retinal Neovessels.
Shuhei Tara - One of the best experts on this subject based on the ideXlab platform.
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differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long term implantation studies with computational modeling
Acta Biomaterialia, 2019Co-Authors: Mark W Maxfield, Hirotsugu Kurobe, Kevin A Rocco, Cameron A Best, Jason M Szafron, Jacob Zbinden, Ethan W Dean, Shuhei TaraAbstract:Abstract Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-e-caprolactone-co-L-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated excellent physiologic graft function, characterized by 100% patency and excellent luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of polymer degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo . Statement of Significance Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of polymer degradation. While venous implants formed viable Neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond polymer degradation.
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targeted imaging of matrix metalloproteinase activity in the evaluation of remodeling tissue engineered vascular grafts implanted in a growing lamb model
The Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Mitchel R Stacy, Yuji Naito, Toshiharu Shinoka, Mark W Maxfield, Hirotsugu Kurobe, Shuhei Tara, Chung Chan, Kevin A Rocco, Albert J Sinusas, Christopher K. BreuerAbstract:Objectives The clinical translation of tissue-engineered vascular grafts has been demonstrated in children. The remodeling of biodegradable, cell-seeded scaffolds to functional Neovessels has been partially attributed to matrix metalloproteinases. Noninvasive assessment of matrix metalloproteinase activity can indicate graft remodeling and elucidate the progression of neovessel formation. Therefore, matrix metalloproteinase activity was evaluated in grafts implanted in lambs using in vivo and ex vivo hybrid imaging. Graft growth and remodeling was quantified using in vivo x-ray computed tomography angiography. Methods Cell-seeded and unseeded scaffolds were implanted in 5 lambs as inferior vena cava interposition grafts. At 2 and 6 months after implantation, in vivo angiography was used to assess graft morphology. In vivo and ex vivo single photon emission tomography/computed tomography imaging was performed with a radiolabeled compound targeting matrix metalloproteinase activity at 6 months. The neotissue was examined at 6 months using qualitative histologic and immunohistochemical staining and quantitative biochemical analysis. Results The seeded grafts demonstrated significant luminal and longitudinal growth from 2 to 6 months. In vivo imaging revealed subjectively greater matrix metalloproteinase activity in grafts versus native tissue. Ex vivo imaging confirmed a quantitative increase in matrix metalloproteinase activity and demonstrated greater activity in unseeded versus seeded grafts. The glycosaminoglycan content was increased in seeded grafts versus unseeded grafts, without significant differences in collagen content. Conclusions Matrix metalloproteinase activity remained elevated in tissue-engineered grafts 6 months after implantation and could indicate remodeling. Optimization of in vivo imaging to noninvasively evaluate matrix metalloproteinase activity could assist in the serial assessment of vascular graft remodeling.