Applications of computational models to better understand microvascular remodelling: a focus on biomechanical integration across scales

Murfee, Walter L.; Sweat, Richard; Tsubota, Kazuo; Gabhann, Feilim Mac; Khismatullin, Damir B.; Peirce, Shayn M.

doi:10.1098/rsfs.2014.0077

Cited by 15 publications

(12 citation statements)

References 107 publications

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“…Multiscale modeling in biomechanics focuses on describing the complex mechanical behavior of organisms at multiple length and time scales (e.g., organ, tissue, cells, molecules) and the resulting effects of mechanical forces on cell response 1,2 . This conceptual framework has gained increasing traction in musculoskeletal systems: while osteoarthritis (OA) is acknowledged to be a disease of the entire joint as an organ, macroscale mechanical forces associated with joint kinematics and aspects of gait are ultimately translated into nanoscale forces at the level of individual extracellular matrix (ECM) and cytoskeletal macromolecules 3 .…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis year in review 2015: mechanics

Varady

Grodzinsky

2016

Osteoarthritis and Cartilage

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Motivated by the conceptual framework of multi-scale biomechanics, this narrative review highlights recent major advances with a focus on gait and joint kinematics, then tissue-level mechanics, cell mechanics and mechanotransduction, matrix mechanics, and finally the nanoscale mechanics of matrix macromolecules. A literature review was conducted from January 2014 to April 2015 using PubMed to identify major developments in mechanics related to osteoarthritis (OA). Studies of knee adduction, flexion, rotation, and contact mechanics have extended our understanding of medial compartment loading. In turn, advances in measurement methodologies have shown how injuries to both the meniscus and ligaments, together, can alter joint kinematics. At the tissue scale, novel findings have emerged regarding the mechanics of the meniscus as well as cartilage superficial zone. Moving to the cell level, poroelastic and poroviscoelastic mechanisms underlying chondrocyte deformation have been reported, along with the response to osmotic stress. Further developments have emerged on the role of calcium signaling in chondrocyte mechanobiology, including exciting findings on the function of mechanically activated cation channels newly found to be expressed in chondrocytes. Finally, AFM-based nano-rheology systems have enabled studies of thin murine tissues and brush layers of matrix molecules over a wide range of loading rates including high rates corresponding to impact injury. With OA acknowledged to be a disease of the joint as an organ, understanding mechanical behavior at each length scale helps to elucidate the connections between cell biology, matrix biochemistry and tissue structure/function that may play a role in the pathomechanics of OA.

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Section: Introductionmentioning

confidence: 99%

Osteoarthritis year in review 2015: mechanics

Varady

Grodzinsky

2016

Osteoarthritis and Cartilage

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“…Computer simulations have been developed for sprouting angiogenesis [159–161] (Fig. 2b), systemic and localized growth factor kinetics [162, 163], and microvascular biomechanics [164], as well as for oxygen/nutrient exchange within tissue microcirculation [101, 165] and drug delivery across the microvessel wall [166]. Endothelial cells have been the focus for many of these models, but as we learn more about how pericytes influence endothelial cell function (and vice versa), it will be important to build upon previous models and incorporate the pericyte compartment into the parameter space, rule sets, and governing algorithms.…”

Section: Computational Modeling Of Microvascular Pericytesmentioning

confidence: 99%

“…Experimental observation of these events yields data sets from various levels including transcriptional, molecular, and cellular. This information guides model construction with regard to rule sets for specific cell activities such as endothelial cell migration or filopodial extensions, as seen in agent-based modeling (ABM) approaches [159, 164, 167]. Multi-scale models couple these actions to underlying molecular pathways and kinetic modeling where each molecular species is accounted for by specific equations [158] (Fig.…”

Section: Computational Modeling Of Microvascular Pericytesmentioning

confidence: 99%

Microvascular bioengineering: a focus on pericytes

Zhao

Chappell

2019

J Biol Eng

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Capillaries within the microcirculation are essential for oxygen delivery and nutrient/waste exchange, among other critical functions. Microvascular bioengineering approaches have sought to recapitulate many key features of these capillary networks, with an increasing appreciation for the necessity of incorporating vascular pericytes. Here, we briefly review established and more recent insights into important aspects of pericyte identification and function within the microvasculature. We then consider the importance of including vascular pericytes in various bioengineered microvessel platforms including 3D culturing and microfluidic systems. We also discuss how vascular pericytes are a vital component in the construction of computational models that simulate microcirculation phenomena including angiogenesis, microvascular biomechanics, and kinetics of exchange across the vessel wall. In reviewing these topics, we highlight the notion that incorporating pericytes into microvascular bioengineering applications will increase their utility and accelerate the translation of basic discoveries to clinical solutions for vascular-related pathologies.

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“…Many papers highlight the importance of computational multi-scale methods in systems biology [9][10][11][12][13] and recently, in the biofabrication [14]. The biological systems are made up of many spatial and temporal scales.…”

Section: Biological Computational Aided Engineering For Biofabricatiomentioning

confidence: 99%

BioCAE: A New Strategy of Complex Biological Systems for Biofabrication of Tissues and Organs

Dernowsek¹,

Ra²,

Silva³

2017

J Tissue Sci Eng

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Next sessions we expose a new approach, based on Information *Corresponding author: Janaina de Andrea Dernowsek, Center for information technology Renato Archer (CTI), 3D Technologies Research Group (NT3D), Campinas, Brazil, AbstractBiofabrication as an interdisciplinary area is fostering new knowledge and integration of areas like nanotechnology, chemistry, biology, physics, materials science, control systems, among many others, necessary to accomplish the challenge of bioengineering functional complex tissues. The emergence of integrated platforms and systems biology to understand complex biological systems in multiscale levels will enable the prediction and creation of biofabricated biological structures. This systematic analysis (meta-analysis) or integrated platforms for estimating biological process have been named as BioCAE, which will become the key for important steps of the biofabrication processes. Biological Computational Aided Engineering (BioCAE) is a new computational approach to understanding and bioengineer complex tissues (biofabrication) using a combination of different methods as multiscale modelling, computer simulations, data mining and systems biology. In addition, multi-agent systems (MAS), which are composed of different interacting computing entities called agents, also provide an interesting way to design and implement simulations of biological systems, integrating them with all steps of the BioCAE. MAS as a part of computational science have become a growing area to manipulate and solve complex problems. This paper presents an approach that will allow predicting the development and behavior of different biological processes such as molecular networks, gene interactions, cells, tissues and organs due to its flexibility, beyond to provide a new outlook in the biofabrication of tissues and organs.

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Applications of computational models to better understand microvascular remodelling: a focus on biomechanical integration across scales

Cited by 15 publications

References 107 publications

Osteoarthritis year in review 2015: mechanics

Osteoarthritis year in review 2015: mechanics

Microvascular bioengineering: a focus on pericytes

BioCAE: A New Strategy of Complex Biological Systems for Biofabrication of Tissues and Organs

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