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Can Mathematics and Computational Modeling Help Treat Deep Tissue Injuries?

ABSTRACT: Objective: Improving the treatment of deep tissue injuries, such as burns, by the use of computational modeling, instead of by animal experiments. Approach: Development of mathematical relations between various parameters and processes. Furthermore, solving the resulting problems through the use of numerical methods, such as finite-element methods. Results: Using our framework, we are able to simulate wound contraction in two dimensions, in which the wound area is followed over time. Our studies indicate that the degree of contraction can be reduced if the appearance of myofibroblasts is inhibited and if their apoptosis is enhanced. Furthermore, after skin grafting, splinting procedures are to be continued as long as TG-beta like growth factor levels are significant. Innovation: A morphoelasticity-based and computational-probabilistic framework for studying the evolution of burn injuries. Conclusion: The current framework is able to reproduce the time evolution of the wound area as observed in clinical results for skin grafts.

SUBMITTER: Vermolen F

PROVIDER: S-EPMC6862969 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Can Mathematics and Computational Modeling Help Treat Deep Tissue Injuries?

Vermolen Fred F van Zuijlen Paul P

Advances in wound care 20191106 12

Objective: Improving the treatment of deep tissue injuries, such as burns, by the use of computational modeling, instead of by animal experiments. Approach: Development of mathematical relations between various parameters and processes. Furthermore, solving the resulting problems through the use of numerical methods, such as finite-element methods. Results: Using our framework, we are able to simulate wound contraction in two dimensions, in which the wound area is followed o ...[more]

PMID: 31750017

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Project description:To understand how excitable tissues give rise to arrhythmias, it is crucially necessary to understand the electrical dynamics of cells in the context of their environment. Multicellular monolayer cultures have proven useful for investigating arrhythmias and other conduction anomalies, and because of their relatively simple structure, these constructs lend themselves to paired computational studies that often help elucidate mechanisms of the observed behavior. However, tissue cultures of cardiomyocyte monolayers currently require the use of neonatal cells with ionic properties that change rapidly during development and have thus been poorly characterized and modeled to date. Recently, Kirkton and Bursac demonstrated the ability to create biosynthetic excitable tissues from genetically engineered and immortalized HEK293 cells with well-characterized electrical properties and the ability to propagate action potentials. In this study, we developed and validated a computational model of these excitable HEK293 cells (called "Ex293" cells) using existing electrophysiological data and a genetic search algorithm. In order to reproduce not only the mean but also the variability of experimental observations, we examined what sources of variation were required in the computational model. Random cell-to-cell and inter-monolayer variation in both ionic conductances and tissue conductivity was necessary to explain the experimentally observed variability in action potential shape and macroscopic conduction, and the spatial organization of cell-to-cell conductance variation was found to not impact macroscopic behavior; the resulting model accurately reproduces both normal and drug-modified conduction behavior. The development of a computational Ex293 cell and tissue model provides a novel framework to perform paired computational-experimental studies to study normal and abnormal conduction in multidimensional excitable tissue, and the methodology of modeling variation can be applied to models of any excitable cell.

Dataset Information

Can Mathematics and Computational Modeling Help Treat Deep Tissue Injuries?

Publications

Can Mathematics and Computational Modeling Help Treat Deep Tissue Injuries?

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