scholarly journals Multiscale Mechanical Simulations of Cell Compacted Collagen Gels

2013 ◽  
Vol 135 (7) ◽  
Author(s):  
Maziar Aghvami ◽  
V. H. Barocas ◽  
E. A. Sander

Engineered tissues are commonly stretched or compressed (i.e., conditioned) during culture to stimulate extracellular matrix (ECM) production and to improve the mechanical properties of the growing construct. The relationships between mechanical stimulation and ECM remodeling, however, are complex, interdependent, and dynamic. Thus, theoretical models are required for understanding the underlying phenomena so that the conditioning process can be optimized to produce functional engineered tissues. Here, we continue our development of multiscale mechanical models by simulating the effect of cell tractions on developing isometric tension and redistributing forces in the surrounding fibers of a collagen gel embedded with explants. The model predicted patterns of fiber reorganization that were similar to those observed experimentally. Furthermore, the inclusion of cell compaction also changed the distribution of fiber strains in the gel compared to the acellular case, particularly in the regions around the cells where the highest strains were found.

2012 ◽  
Vol 706-709 ◽  
pp. 449-454
Author(s):  
Eugenia Blangino ◽  
Martín A. Cagnoli ◽  
Ramiro M. Irastorza ◽  
Fernando Vericat

It is of great interest in tissue engineering the role of collagen gel-based structures (scaffolds, grafts and-by cell seeded and maturation-tissue equivalents (TEs) for several purposes). It is expected the appropriate biological compatibility when the extracellular matrix (ECM) is collagen-based. Regarding the mechanical properties (MP), great efforts in tissue engineering are focused in tailoring TE properties by controlling ECM composition and organization. When cells are seeded, the collagen network is remodeled by cell-driven compaction and consolidation, produced mainly through the mechanical stimuli that can be directed selecting the geometry and the surfaces exposed to the cells. Collagen gels have different (chemical and mechanical) properties depending on their origin and preparation conditions. The MP of the collagen network are derived from the degree of cross-linking (CLD) which can be modified by different treatments. One of the techniques to evaluate MP in the network is by ultrasound (US). In this work we analyse the effect of several mechanical constraints (similar to that imposed to promote cell growth on certain sample surfaces, when seeded) on samples of gelatin with a specific geometry (thick walls cylinders) under loading conditions of pulsatile flow. We checked US parameters and estimates evolution of the network structure for different restrictions in the sample mobility. It was implemented by adapting devices specially built to measure elastic properties of biological tissues by US. The material (origin and purity) and the preparation conditions for the gelatin were selected in order to compare the results with those of literature.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247727
Author(s):  
Shayan Shahab ◽  
Mehran Kasra ◽  
Alireza Dolatshahi-Pirouz

Natural biopolymer-based hydrogels especially agarose and collagen gels, considering their biocompatibility with cells and their capacity to mimic biological tissues, have widely been used for in-vitro experiments and tissue engineering applications in recent years; nevertheless their mechanical properties are not always optimal for these purposes. Regarding the importance of the mechanical properties of hydrogels, many mechanical characterization studies have been carried out for such biopolymers. In this work, we have focused on understanding the mechanical role of agarose and collagen concentration on the hydrogel strength and elastic behavior. In this direction, Amirkabir Magnetic Bead Rheometry (AMBR) characterization device equipped with an optimized electromagnet, was designed and constructed for the measurement of hydrogel mechanical properties. The operation of AMBR set-up is based on applying a magnetic field to actuate magnetic beads in contact with the gel surface in order to actuate the gel itself. In simple terms the magnetic beads leads give rise to mechanical shear stress on the gel surface when under magnetic influence and together with the associated bead-gel displacement it is possible to calculate the hydrogel shear modulus. Agarose and Collagen gels with respectively 0.2–0.6 wt % and 0.2–0.5 wt % percent concentrations were prepared for mechanical characterization in terms of their shear modulus. The shear modulus values for the different percent concentrations of the agarose gel were obtained in the range 250–650 Pa, indicating the shear modulus increases by increasing in the agar gel concentration. In addition to this, the values of shear modulus for the collagen gel increase as function of concentration in the range 240–520 Pa in accordance with an approximately linear relationship between collagen concentration and gel strength.


Author(s):  
Stavros Thomopoulos ◽  
Jeffrey W. Holmes

The development of anisotropic mechanical properties is critical for the successful function of many soft tissues. Load bearing tissues naturally develop varying degrees of anisotropy, presumably in response to their specific loading environment. For example, the scar tissue that forms after a myocardial infarction is structurally and mechanically anisotropic. To better understand the scar mechanics, we first need to develop structure-function relationships for collagen fiber networks. In order to improve the healing after myocardial infarction, a better understanding of the mechanical anisotropy is necessary. An in vitro collagen gel system can be used to control individual fiber network components and to determine the effect of each component on the mechanical properties of the gel. Previously, we demonstrated the ability to promote two different collagen gel structures, with two different levels of mechanical anisotropy [1]. The goal of the current study was to quantitatively relate the observed mechanical anisotropy to the collagen fiber structure. It was hypothesized that the anisotropy could be explained with a simple structural model, where the gel behavior is derived from the behavior of the individual fibers within the gel (i.e., the properties of the fibers, their orientation, and their level of slack).


Author(s):  
Ryan M. Dean ◽  
Edward A. Sander ◽  
Victor H. Barocas

Due to collagen’s importance as an extracellular matrix (ECM) structural protein, it has often been used as a scaffold material for engineered or model tissue [1]. In order to correctly generate new tissues, the scaffolding must mimic the native ECM. The mechanical properties are crucial not only as a structural support but also to allow for cell differentiation [1]. Preconditioning is a processing technique where a sample of soft tissue material is subjected to cyclical strain. As a result, the fibers align in accordance with the direction of preconditioning [2]. Such realignment alters the mechanical properties of the tissue. In order to design more effective tissue engineering scaffolds, it is important to characterize the effects of preconditioning on the damage and failure of collagen constructs. This study attempts to understand how preconditioning alters the stresses, strains, and failure of a sample when it is subjected to a load in different orientations.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ramiro M. Irastorza ◽  
Bernard Drouin ◽  
Eugenia Blangino ◽  
Diego Mantovani

Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.


Soft Matter ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 574-580 ◽  
Author(s):  
A. J. Holder ◽  
N. Badiei ◽  
K. Hawkins ◽  
C. Wright ◽  
P. R. Williams ◽  
...  

It is shown herein that it is possible to control the mechanical and microstructural properties of collagen gels by manipulating temperature in the vicinity of the sol–gel transition; the Fractional Maxwell Model is also shown to accurately describe the rheological behaviour of such gels.


Author(s):  
Harini G. Sundararaghavan ◽  
David I. Shreiber

One approach to enhance nerve and spinal cord regeneration following injury is to implant a biomaterial scaffold to ”bridge” the gap of the injury. Structural/mechanical anisotropy has been suggested as a means of orienting this growth axially. We have spatially varied the mechanical properties of a 3D collagen gel to direct growth axially and unidirectionally. Gradients of mechanical properties were generated in collagen gels by exposing the collagen to a 0–1mM gradient of genipin, a cell-tolerated crosslinking agent, for 12hrs via microfluidics. The gradient of stiffness was confirmed via a gradient of genipin-induced fluorescence intensity, which we have previously correlated to the storage modulus of collagen gels. The growth of neurites from isolated chick embryo dorsal root ganglia (DRG) in the presence of these gradients was evaluated after 5 days in culture. In control cases, neurites grew into the collagen gel and up either side of the cross-channel to approximately equal lengths. A 20% difference in differential growth was observed in control experiments. In contrast, when presented a gradient of shear modulus from ∼365Pa – 60Pa, neurites elected to grow down the gradient of stiffness to the compliant side, with an almost 300% difference. Interestingly, the length of neurites in gels with gradients was significantly greater than the length of those grown in gels with uniform, untreated gels with high compliance. Control of neurite growth, cell migration, and other aspects of cell behavior in 3D scaffolds via mechanical properties offers vast potential for tissue engineering and other regenerative therapies.


2013 ◽  
Vol 305 (12) ◽  
pp. E1427-E1435 ◽  
Author(s):  
Nadia Alkhouli ◽  
Jessica Mansfield ◽  
Ellen Green ◽  
James Bell ◽  
Beatrice Knight ◽  
...  

Adipose tissue (AT) expansion in obesity is characterized by cellular growth and continuous extracellular matrix (ECM) remodeling with increased fibrillar collagen deposition. It is hypothesized that the matrix can inhibit cellular expansion and lipid storage. Therefore, it is important to fully characterize the ECM's biomechanical properties and its interactions with cells. In this study, we characterize and compare the mechanical properties of human subcutaneous and omental tissues, which have different physiological functions. AT was obtained from 44 subjects undergoing surgery. Force/extension and stress/relaxation data were obtained. The effects of osmotic challenge were measured to investigate the cellular contribution to tissue mechanics. Tissue structure and its response to tensile strain were determined using nonlinear microscopy. AT showed nonlinear stress/strain characteristics of up to a 30% strain. Comparing paired subcutaneous and omental samples ( n = 19), the moduli were lower in subcutaneous: initial 1.6 ± 0.8 (means ± SD) and 2.9 ± 1.5 kPa ( P = 0.001), final 11.7 ± 6.4 and 32 ± 15.6 kPa ( P < 0.001), respectively. The energy dissipation density was lower in subcutaneous AT ( n = 13): 0.1 ± 0.1 and 0.3 ± 0.2 kPa, respectively ( P = 0.006). Stress/relaxation followed a two-exponential time course. When the incubation medium was exchanged for deionized water in specimens held at 30% strain, force decreased by 31%, and the final modulus increased significantly. Nonlinear microscopy revealed collagen and elastin networks in close proximity to adipocytes and a larger-scale network of larger fiber bundles. There was considerable microscale heterogeneity in the response to strain in both cells and matrix fibers. These results suggest that subcutaneous AT has greater capacity for expansion and recovery from mechanical deformation than omental AT.


Author(s):  
J. J. Finkbiner ◽  
K. L. Harrigan ◽  
K. C. Dee ◽  
G. A. Livesay

Collagen plays an important structural role in many natural tissues, such as ligaments and tendons. Due to its ubiquity in the human body and its commercial availability, biomaterials using collagen gel as a scaffold for an extracellular matrix are being developed as alternative treatments for soft tissue injuries [1]. The use of collagen fibers as a matrix in cell-seeded collagen gels has been shown to limit contraction of the gels as well as increase scaffold permeability and cell viability [2,3]. Additionally, it has been found that dehydration of collagen fibers increases fiber strength [4]. Therefore, investigating the effect of changing fiber shape to increase fiber surface and gel/fiber interaction is important.


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