Efficient computational simulation of actin stress fiber remodeling

Ristori, Tommaso; Obbink-Huizer, C Christine; Oomens, Cwj Cees; Baaijens, Fpt Frank; Loerakker, Sandra

doi:10.1080/10255842.2016.1140748

Cited by 12 publications

(12 citation statements)

References 33 publications

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“…Because models are inherently a simplification of reality, we only included the subset of tissue components that are most strongly associated with mechanically induced tissue remodeling. We validated the individual aspects of the model on several cases of soft tissue remodeling featuring different geometries and loading conditions in previous works (34,(36)(37)(38). We derived the material parameters associated with the stiffness of collagen fibers from equibiaxial tensile tests.…”

Section: Limitationsmentioning

confidence: 99%

“…Prediction of in vivo remodeling and functionality from the initial valve properties We used computational modeling (34,(36)(37)(38) to predict the in vivo remodeling of TEHVs in response to dynamic pressure variations, starting from the initial geometry and material properties before implantation (see the "Computational prediction of valve functionality and remodeling" section of Supplementary Materials and Methods for a detailed description). Systematic variations of leaflet thickness and cell contractility were performed to assess their role in ensuring functional remodeling.…”

Section: Transcatheter Implantation Of Tehvs As Pulmonary Valve Replamentioning

confidence: 99%

“…Detailed description of the methodologies used is reported in the "Computational prediction of valve functionality and remodeling" section of Supplementary Materials and Methods. Prediction of in vivo remodeling from initial tissue properties Starting from the geometry and average material properties of the control valves, in vivo remodeling of the TEHVs was predicted using our recently developed computational framework, describing the processes of cell orientation, reorientation, cell contractility, cell-mediated collagen contraction, and collagen turnover in response to mechanical stimuli (see the "Computational prediction of valve functionality and remodeling" section of Supplementary Materials and Methods for additional information) (34,(36)(37)(38). Dynamic pulmonary loading conditions were applied, assuming that the maximum trans-valvular pressure difference equals 15 mmHg.…”

Section: Computational Prediction Of Valve Functionality and Remodelimentioning

confidence: 99%

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Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model

et al. 2018

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Valvular heart disease is a major cause of morbidity and mortality worldwide. Current heart valve prostheses have considerable clinical limitations due to their artificial, nonliving nature without regenerative capacity. To overcome these limitations, heart valve tissue engineering (TE) aiming to develop living, native-like heart valves with self-repair, remodeling, and regeneration capacity has been suggested as next-generation technology. A major roadblock to clinically relevant, safe, and robust TE solutions has been the high complexity and variability inherent to bioengineering approaches that rely on cell-driven tissue remodeling. For heart valve TE, this has limited long-term performance in vivo because of uncontrolled tissue remodeling phenomena, such as valve leaflet shortening, which often translates into valve failure regardless of the bioengineering methodology used to develop the implant. We tested the hypothesis that integration of a computationally inspired heart valve design into our TE methodologies could guide tissue remodeling toward long-term functionality in tissue-engineered heart valves (TEHVs). In a clinically and regulatory relevant sheep model, TEHVs implanted as pulmonary valve replacements using minimally invasive techniques were monitored for 1 year via multimodal in vivo imaging and comprehensive tissue remodeling assessments. TEHVs exhibited good preserved long-term in vivo performance and remodeling comparable to native heart valves, as predicted by and consistent with computational modeling. TEHV failure could be predicted for nonphysiological pressure loading. Beyond previous studies, this work suggests the relevance of an integrated in silico, in vitro, and in vivo bioengineering approach as a basis for the safe and efficient clinical translation of TEHVs.

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Section: Limitationsmentioning

confidence: 99%

Section: Transcatheter Implantation Of Tehvs As Pulmonary Valve Replamentioning

confidence: 99%

Section: Computational Prediction Of Valve Functionality and Remodelimentioning

confidence: 99%

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Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model

et al. 2018

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“…Due to the temporal periodicity of the intracellular signal S and the slow remodeling of C, it was possible to approximate the solution of Eq. 11 by using a similar approach as reported in Ristori et al (44), thereby further decreasing the computational costs:…”

Section: Fa Intracellular Signaling Cascadementioning

confidence: 99%

Prediction of Cell Alignment on Cyclically Strained Grooved Substrates

Ristori

Vigliotti

Baaijens

et al. 2016

Biophysical Journal

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Cells respond to both mechanical and topographical stimuli by reorienting and reorganizing their cytoskeleton. Under certain conditions, such as for cells on cyclically stretched grooved substrates, the effects of these stimuli can be antagonistic. The biophysical processes that lead to the cellular reorientation resulting from such a competition are not clear yet. In this study, we hypothesized that mechanical cues and the diffusion of the intracellular signal produced by focal adhesions are determinants of the final cellular alignment. This hypothesis was investigated by means of a computational model, with the aim to simulate the (re)orientation of cells cultured on cyclically stretched grooved substrates. The computational results qualitatively agree with previous experimental studies, thereby supporting our hypothesis. Furthermore, cellular behavior resulting from experimental conditions different from the ones reported in the literature was simulated, which can contribute to the development of new experimental designs.

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“…In this context, due to their versatility and predictive potential, computa- 25 tional models can be employed to simulate collagen remodeling and test hypotheses. Early computational models have confirmed the importance of mechanical stimuli for the collagen remodeling occurring in heart valves [10,11].…”

Section: Introductionmentioning

confidence: 99%

Predicting and understanding collagen remodeling in human native heart valves during early development

et al. 2018

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The hemodynamic functionality of heart valves strongly depends on the distribution of collagen fibers, which are their main load-bearing constituents. It is known that collagen networks remodel in response to mechanical stimuli. Yet, the complex interplay between external load and collagen remodeling is poorly understood. In this study, we adopted a computational approach to simulate collagen remodeling occurring in native fetal and pediatric heart valves. The computational model accounted for several biological phenomena: cellular (re)orientation in response to both mechanical stimuli and topographical cues provided by collagen fibers; collagen deposition and traction forces along the main cellular direction; collagen degradation decreasing with stretch; and cell-mediated collagen prestretch. Importantly, the computational results were well in agreement with previous experimental data for all simulated heart valves. Simulations performed by varying some of the computational parameters suggest that cellular forces and (re)orientation in response to mechanical stimuli may be fundamental mechanisms for the emergence of the circumferential collagen alignment usually observed in native heart valves. On the other hand, the tendency of cells to coalign with collagen fibers is essential to maintain and reinforce that circumferential alignment during development. STATEMENT OF SIGNIFICANCE: The hemodynamic functionality of heart valves is strongly influenced by the alignment of load-bearing collagen fibers. Currently, the mechanisms that are responsible for the development of the circumferential collagen alignment in native heart valves are not fully understood. In the present study, cell-mediated remodeling of native human heart valves during early development was computationally simulated to understand the impact of individual mechanisms on collagen alignment. Our simulations successfully predicted the degree of collagen alignment observed in native fetal and pediatric semilunar valves. The computational results suggest that the circumferential collagen alignment arises from cell traction and cellular (re)orientation in response to mechanical stimuli, and with increasing age is reinforced by the tendency of cells to co-align with pre-existing collagen fibers.

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Efficient computational simulation of actin stress fiber remodeling

Cited by 12 publications

References 33 publications

Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model

Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model

Prediction of Cell Alignment on Cyclically Strained Grooved Substrates

Predicting and understanding collagen remodeling in human native heart valves during early development

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