Computer Model-Driven Design in Cardiovascular Regenerative Medicine

Loerakker, Sandra; Humphrey, Jay D.

doi:10.1007/s10439-022-03037-5

Cited by 8 publications

(4 citation statements)

References 86 publications

(104 reference statements)

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“…Thus, the mechanical behavior and loaded geometries of the vessel are simulated, and different constitutive parameters that govern the kinetics can be used to test certain hypotheses. 79 Notably, these models have uncovered the mechanism governing the formation and resolution of stenosis in tissue-engineered vascular grafts for the Fontan procedure, which results from an exuberant foreign body response followed by inhibition of new matrix deposition via mechanobiological stimuli. 21,78 Extensions to this framework have included 3D geometries for simulating focal narrowing, 80 as well as true patient-specific geometries and 3D fluid dynamics that allow better understanding of spatial differences in remodeling within a graft.…”

Section: Fundamentals Of Computational Experimental and Animal Modelsmentioning

confidence: 99%

Hemodynamics and Wall Mechanics of Vascular Graft Failure

Szafron,

Heng,

Boyd

et al. 2024

ATVB

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Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall via activation of mechanosensitive signaling pathways and subsequent changes in gene expression and associated turnover of cells and extracellular matrix. In this review, we outline experimental and computational tools used to quantify metrics of biomechanical loading in vascular grafts and highlight those that show potential in predicting graft failure for diverse disease contexts. We include metrics derived from both fluid and solid mechanics that drive feedback loops between mechanobiological processes and changes in the biomechanical state that govern the natural history of vascular grafts. As illustrative examples, we consider application-specific coronary artery bypass grafts, peripheral vascular grafts, and tissue-engineered vascular grafts for congenital heart surgery as each of these involves unique circulatory environments, loading magnitudes, and graft materials.

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Section: Fundamentals Of Computational Experimental and Animal Modelsmentioning

confidence: 99%

Hemodynamics and Wall Mechanics of Vascular Graft Failure

Szafron,

Heng,

Boyd

et al. 2024

ATVB

Self Cite

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“…Given the large number of variables involved in tissue engineering design, simulation-based methods are highly attractive [17][18][19]. Computational tools allow the prediction of the entire ETR process.…”

Section: Introductionmentioning

confidence: 99%

Modelling the anisotropic inelastic response of polymeric scaffolds for in situ tissue engineering applications

Terzano,

Wollner,

Kainz

et al. 2023

J. R. Soc. Interface.

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In situ tissue engineering offers an innovative solution for replacement valves and grafts in cardiovascular medicine. In this approach, a scaffold, which can be obtained by polymer electrospinning, is implanted into the human body and then infiltrated by cells, eventually replacing the scaffold with native tissue. In silico simulations of the whole process in patient-specific models, including implantation, growth and degradation, are very attractive to study the factors that might influence the end result. In our research, we focused on the mechanical behaviour of the polymeric scaffold and its short-term response. Following a recently proposed constitutive model for the anisotropic inelastic behaviour of fibrous polymeric materials, we present here its numerical implementation in a finite element framework. The numerical model is developed as user material for commercial finite element software. The verification of the implementation is performed for elementary deformations. Furthermore, a parallel-plate test is proposed as a large-scale representative example, and the model is validated by comparison with experiments.

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“…The common computational models are based on incorporating growth and remodeling constitutive laws into finite element models. In ECM remodeling models, ECM fibers are treated as a network of one-dimensional structures that grow and reorient over time (Thomas et al 2019); and in constrained mixture theory-based models, tissues are modeled as a mixture of different constituents that follow mass balance laws (Soares andSacks 2016, Loerakker andHumphrey 2023). These tissue growth and remodeling models take mechanical material properties and loading conditions as inputs and can predict ECM realignment or deformation of the entire tissue, respectively.…”

Section: Introductionmentioning

confidence: 99%

Reducing retraction in engineered tissues through design of sequential growth factor treatment

Lei

Mungai

et al. 2023

Biofabrication

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Heart valve disease is associated with high morbidity and mortality worldwide resulting in hundreds of thousands of heart valve replacements each year. Tissue engineered heart valves (TEHVs) have the potential to overcome the major limitations of traditional replacement valves; however, leaflet retraction has led to the failure of TEHVs in preclinical studies. Sequentially varying growth factors over time has been utilized to promote maturation of engineered tissues and may be effective in reducing tissue retraction, yet it is difficult to predict the effects of such treatments due to complex between the cells and the extracellular matrix (ECM), biochemical environment, and mechanical stimuli. We hypothesize that sequential treatments of FGF2 and TGF-β1 can be used to minimize cell-generated tissue retraction by decreasing active cell contractile forces exerted on the ECM and by inducing the cells to increase the ECM stiffness. Using a custom culturing and monitoring system for 3D tissue constructs, we designed and tested various TGF-β1 and FGF-2 based growth factor treatments, and successfully reduced tissue retraction by 85% and increased the ECM elastic modulus by 260% compared to non growth factor-treated controls, without significantly increasing the contractile force. We also developed and verified a mathematical model to predict the effects of various temporal variations in growth factor treatments and analyzed relationships between tissue properties, the contractile forces, and retraction. These findings improve our understanding of growth factor-induced cell-ECM biomechanical interactions which can inform the design of next generation TEHVs with reduced retraction. The mathematical models could also potentially be applied towards fast screening and optimizing growth factors for use in treatment of diseases including fibrosis.

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Computer Model-Driven Design in Cardiovascular Regenerative Medicine

Cited by 8 publications

References 86 publications

Hemodynamics and Wall Mechanics of Vascular Graft Failure

Hemodynamics and Wall Mechanics of Vascular Graft Failure

Modelling the anisotropic inelastic response of polymeric scaffolds for in situ tissue engineering applications

Reducing retraction in engineered tissues through design of sequential growth factor treatment

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