Computational Modeling of Tissue Self-Assembly

Neagu, Adrian; Kosztin, Ioan; Jakab, Károly; Barz, Bogdan; Neagu, Monica; Jamison, Richard M.; Forgács, Gabor

doi:10.1007/978-3-642-21913-9_13

Cited by 14 publications

(17 citation statements)

References 16 publications

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“…The KMC simulations were then used to quantitatively predict the time evolution of post printing tissue structures in several geometries relevant to animal organs or organ parts, such as rings (Figure 2), sheets (Figure 3), and tubes in the mammalian lung, or small capillaries of the vasculature. 3,31,40 We also used the KMC method to study the process of cell sorting within cellular aggregate fusion formed by multiple types of cells with different adhesivities. This study is directly related to biofabrication of vascular veins with the cellular spheroids made up of mixed smooth muscle cells (SMCs) and endothelial cells (ECs), where lumenized vascular veins are fabricated (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

“…Examples of these models can be found in. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In the agent based approach, we design fundamental rules for neighboring agents (cells in the context of aggregates) to interact with neighboring cells or particles. These probabilistic rules coupled with the fluctuation dynamics can lead to the desired collective or mesoscopic dynamics.…”

Section: Mathematical Modelsmentioning

confidence: 99%

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In-Silico Analysis on 3D Biofabrication Using Kinetic Monte Carlo Simulations

Sun

Wang

2017

ATROA

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We present a three-dimensional (3D) lattice model based on the differential adhesion hypothesis (DAH) to study self-assembly and fusion of multicellular aggregates, which forms the foundation for the scaffold-less biofabrication of tissues and organs, known as "bio-printing". In this new technology, live multicellular aggregates are used as bio-ink to make tissue or organ constructs via the layer-by-layer deposition technique in biocompatible hydrogels; the printed bio-constructs embedded in the hydrogels are then placed in bioreactors to undergo the fusion process to form the desired functional tissue or organ products. Our in-silico approach is an agent-based method, which uses the kinetic Monte Carlo (KMC) algorithm to evolve the cellular system on a 3D lattice. In this model, the cells and the hydrogel media, in which cells are embedded, are coarse-grained to material's points on the lattice, where the cellcell and cell-medium interaction are quantified by adhesion and cohesion energies. In a multicellular aggregate system with a fixed number of cells and fixed amount of hydrogel media, the effect of cell differentiation, proliferation, and death are tactically neglected in the current model, which can be readily included in the model, and the interaction s primarily dictated by the interfacial energy between cell and cell as well as between cells and medium particles on the lattice, respectively. The KMC method is applicable to transient simulations of fusion of multicellular aggregates at the time and length scale appropriate to biofabrication. Numerical experiments are presented to demonstrate fusion and cell sorting during tissue and organ maturation processes.

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Section: Resultsmentioning

confidence: 99%

Section: Mathematical Modelsmentioning

confidence: 99%

In-Silico Analysis on 3D Biofabrication Using Kinetic Monte Carlo Simulations

Sun

Wang

2017

ATROA

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“…A model cell aggregate is placed next to a planar surface of a model biomaterial and cell spreading is studied for various values of the cell-cell and cell-biomaterial interaction energies. By our in silico study we aim to validate the Monte Carlo approach proposed by our group for simulating cell seeding of tissue engineering scaffolds [6].…”

mentioning

confidence: 99%

“…The lattice sites located around the cell aggregate at 0 z z > are occupied by medium particles, thus achieving a model for the cell aggregate bathed in culture medium. In the region where 0 z z ≤ , each node of the network is occupied by an immobile particle, this area representing the biomaterial (scaffold); we study the spreading of cells on the surface of this biomaterial [6]. To visualize the model system, we use the Visual Molecular Dynamics (VMD) software [9].…”

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confidence: 99%

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Cell spreading on biocompatible materials studied by computer simulations

Robu

Stoicu-Tivadar

Neagu

2011

2011 6th IEEE International Symposium on Applied Computational Intelligence and Informatics (SACI)

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The goal of tissue engineering is to create functional tissue constructs that can be implanted into the human organism. A classical approach to tissue engineering consists in the culturing of cells on porous scaffolds made of biocompatible and biodegradable materials. An important step in this approach is the cell seeding of scaffolds. It has been shown that uniform seeding leads to faster development of the tissue construct and superior mechanical properties in comparison to non-uniform seeding. The success of seeding depends on cell spreading on the scaffold's material. This paper presents a computational model of a biological system used in experiments on cell spreading on biomaterials. The model describes a cell aggregate placed on a parallelepipedic slab of biomaterial bathed in cell culture medium. Experiments suggest that cell spreading results from a competition between cell-cell and cell-biomaterial interactions, in accord with Steinberg's differential adhesion hypothesis, which considers that the cellular system evolves towards the state of minimum energy of adhesion. Using the Metropolis Monte Carlo method, we simulated cell spreading on a biomaterial for different values of the cell-cell and cell-biomaterial interactions and found that cell spreading is governed by the difference between half the cell-cell cohesion energy and the cellbiomaterial adhesion energy.

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