A Structural Basis for Anisotropy in Cardiac Fibroblast Populated Collagen Gels

2004 ◽  
Author(s):  
Stavros Thomopoulos ◽  
Jeffrey W. Holmes
Keyword(s):  
Myocardial Infarction ◽  
Mechanical Properties ◽  
Collagen Fiber ◽  
Collagen Gel ◽  
Mechanical Anisotropy ◽  
Control Individual ◽  
Structural Basis ◽  
Collagen Gels ◽  
Specific Loading ◽  
Anisotropic Mechanical Properties

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).

Development of Anisotropy in Fibroblast Populated Collagen Gels

2002 ◽  
Author(s):  
Stavros Thomopoulos ◽  
Vedran Knezevic ◽  
Kevin D. Costa ◽  
Jeffrey W. Holmes
Keyword(s):  
Mechanical Properties ◽  
Soft Tissues ◽  
Mechanical Load ◽  
The Other ◽  
Collagen Structure ◽  
Collagen Gels ◽  
Specific Loading ◽  
Anisotropic Mechanical Properties ◽  
Muscle Loading ◽  
Heart Wall

The development of anisotropic mechanical properties is critical for the successful tissue engineering of many soft tissues. Load bearing tissues naturally develop varying degrees of anisotropy, presumably in response to their specific loading environment. For example, the heart wall develops a collagen structure that varies in a predictable manner through its depth [1]. Tendon, on the other hand, develops a matrix that does not vary much in orientation and is highly aligned in the direction of muscle loading [2]. These varied levels of anisotropy may be due to inherent differences between the cells in each tissue, to differences in the mechanical load and boundary conditions seen by the cells, or to a combination of these factors.

Collagen Fiber Alignment Does Not Explain Mechanical Anisotropy in Fibroblast Populated Collagen Gels

2007 ◽  
Vol 129 (5) ◽  
pp. 642-650 ◽  
Author(s):  
Stavros Thomopoulos ◽  
Gregory M. Fomovsky ◽  
Preethi L. Chandran ◽  
Jeffrey W. Holmes
Keyword(s):  
Mechanical Behavior ◽  
Network Model ◽  
Continuum Model ◽  
Collagen Fiber ◽  
Collagen Gel ◽  
Mechanical Anisotropy ◽  
Collagen Gels ◽  
Fiber Alignment ◽  
High Degree ◽  
Collagen Fiber Alignment

Many load-bearing soft tissues exhibit mechanical anisotropy. In order to understand the behavior of natural tissues and to create tissue engineered replacements, quantitative relationships must be developed between the tissue structures and their mechanical behavior. We used a novel collagen gel system to test the hypothesis that collagen fiber alignment is the primary mechanism for the mechanical anisotropy we have reported in structurally anisotropic gels. Loading constraints applied during culture were used to control the structural organization of the collagen fibers of fibroblast populated collagen gels. Gels constrained uniaxially during culture developed fiber alignment and a high degree of mechanical anisotropy, while gels constrained biaxially remained isotropic with randomly distributed collagen fibers. We hypothesized that the mechanical anisotropy that developed in these gels was due primarily to collagen fiber orientation. We tested this hypothesis using two mathematical models that incorporated measured collagen fiber orientations: a structural continuum model that assumes affine fiber kinematics and a network model that allows for nonaffine fiber kinematics. Collagen fiber mechanical properties were determined by fitting biaxial mechanical test data from isotropic collagen gels. The fiber properties of each isotropic gel were then used to predict the biaxial mechanical behavior of paired anisotropic gels. Both models accurately described the isotropic collagen gel behavior. However, the structural continuum model dramatically underestimated the level of mechanical anisotropy in aligned collagen gels despite incorporation of measured fiber orientations; when estimated remodeling-induced changes in collagen fiber length were included, the continuum model slightly overestimated mechanical anisotropy. The network model provided the closest match to experimental data from aligned collagen gels, but still did not fully explain the observed mechanics. Two different modeling approaches showed that the level of collagen fiber alignment in our uniaxially constrained gels cannot explain the high degree of mechanical anisotropy observed in these gels. Our modeling results suggest that remodeling-induced redistribution of collagen fiber lengths, nonaffine fiber kinematics, or some combination of these effects must also be considered in order to explain the dramatic mechanical anisotropy observed in this collagen gel model system.

Gradients of Stiffness Guide Neurite Growth in 3D Collagen Gels

2007 ◽  
Author(s):  
Harini G. Sundararaghavan ◽  
David I. Shreiber
Keyword(s):  
Mechanical Properties ◽  
Crosslinking Agent ◽  
Collagen Gel ◽  
Neurite Growth ◽  
Mechanical Anisotropy ◽  
Spinal Cord Regeneration ◽  
Collagen Gels ◽  
Differential Growth ◽  
Biomaterial Scaffold ◽  
3D Collagen

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.

The Effect of Mechanical Constraints on Gelatin Samples under Pulsatile Flux

2012 ◽  
Vol 706-709 ◽  
pp. 449-454
Author(s):  
Eugenia Blangino ◽  
Martín A. Cagnoli ◽  
Ramiro M. Irastorza ◽  
Fernando Vericat
Keyword(s):  
Mechanical Properties ◽  
Tissue Engineering ◽  
Collagen Gel ◽  
Biological Tissues ◽  
Mechanical Stimuli ◽  
Collagen Gels ◽  
Collagen Network ◽  
Mechanical Constraints ◽  
Preparation Conditions ◽  
Biological Compatibility

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.

scholarly journals Design and construction of a novel measurement device for mechanical characterization of hydrogels: A case study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247727
Author(s):  
Shayan Shahab ◽  
Mehran Kasra ◽  
Alireza Dolatshahi-Pirouz
Keyword(s):  
Mechanical Properties ◽  
Shear Modulus ◽  
Magnetic Beads ◽  
Mechanical Characterization ◽  
Collagen Gel ◽  
Biological Tissues ◽  
Elastic Behavior ◽  
Collagen Gels ◽  
Collagen Concentration

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.

The Development of Structural and Mechanical Anisotropy in Fibroblast Populated Collagen Gels

2005 ◽  
Vol 127 (5) ◽  
pp. 742-750 ◽  
Author(s):  
Stavros Thomopoulos ◽  
Gregory M. Fomovsky ◽  
Jeffrey W. Holmes
Keyword(s):  
Structure Function ◽  
Collagen Gel ◽  
Cell Types ◽  
Model System ◽  
Mechanical Anisotropy ◽  
Collagen Gels ◽  
Structural Anisotropy ◽  
Mechanical Constraints ◽  
Collagenous Tissues

An in vitro model system was developed to study structure-function relationships and the development of structural and mechanical anisotropy in collagenous tissues. Fibroblast-populated collagen gels were constrained either biaxially or uniaxially. Gel remodeling, biaxial mechanical properties, and collagen orientation were determined after 72h of culture. Collagen gels contracted spontaneously in the unconstrained direction, uniaxial mechanical constraints produced structural anisotropy, and this structural anisotropy was associated with mechanical anisotropy. Cardiac and tendon fibroblasts were compared to test the hypothesis that tendon fibroblasts should generate greater anisotropy in vitro. However, no differences were seen in either structure or mechanics of collagen gels populated with these two cell types, or between fibroblast populated gels and acellular gels. This study demonstrates our ability to control and measure the development of structural and mechanical anisotropy due to imposed mechanical constraints in a fibroblast-populated collagen gel model system. While imposed constraints were required for the development of anisotropy in this system, active remodeling of the gel by fibroblasts was not. This model system will provide a basis for investigating structure-function relationships in engineered constructs and for studying mechanisms underlying the development of anisotropy in collagenous tissues.

Anisotropic nanomechanical properties of Nephila clavipes dragline silk

2006 ◽  
Vol 21 (8) ◽  
pp. 2035-2044 ◽  
Author(s):  
Donna M. Ebenstein ◽  
Kathryn J. Wahl
Keyword(s):  
Mechanical Properties ◽  
Spider Silk ◽  
Imaging Techniques ◽  
Dynamic Stiffness ◽  
Longitudinal Section ◽  
Mechanical Anisotropy ◽  
Nephila Clavipes ◽  
Silk Fibers ◽  
Reduced Modulus ◽  
Anisotropic Mechanical Properties

Spider silk is a material with unique mechanical properties under tension. In this study, we explore the anisotropic mechanical properties of spider silk using instrumented indentation. Both quasistatic indentation and dynamic stiffness imaging techniques were used to measure the mechanical properties in transverse and longitudinal sections of silk fibers. Quasistatic indentation yielded moduli of 10 ± 2 GPa in transverse sections and moduli of 6.4 ± 0.5 GPa in longitudinal sections, demonstrating mechanical anisotropy in the fiber. This result was supported by dynamic stiffness imaging, which also showed the average reduced modulus measured in the transverse section to be slightly higher than that of the longitudinal section. Stiffness imaging further revealed an oriented microstructure in the fiber, showing microfibrils aligned with the drawing axis of the fiber. No spatial distribution of modulus across the silk sections was observed by either quasistatic or stiffness imaging mechanics.

scholarly journals Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ramiro M. Irastorza ◽  
Bernard Drouin ◽  
Eugenia Blangino ◽  
Diego Mantovani
Keyword(s):  
Mechanical Properties ◽  
Tissue Engineering ◽  
Vascular Tissue ◽  
Nonlinear Models ◽  
Small Diameter ◽  
Collagen Gel ◽  
Vascular Tissue Engineering ◽  
Suitable Model ◽  
Collagen Gels ◽  
Hammerstein Models

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.

scholarly journals Control of collagen gel mechanical properties through manipulation of gelation conditions near the sol–gel transition

Soft Matter ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 574-580 ◽  
Author(s):  
A. J. Holder ◽  
N. Badiei ◽  
K. Hawkins ◽  
C. Wright ◽  
P. R. Williams ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Sol Gel ◽  
Collagen Gel ◽  
Rheological Behaviour ◽  
Maxwell Model ◽  
Microstructural Properties ◽  
Collagen Gels ◽  
Sol Gel Transition ◽  
Mechanical And Microstructural Properties ◽  
Gel Transition

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.

scholarly journals Multiscale Mechanical Simulations of Cell Compacted Collagen Gels

2013 ◽  
Vol 135 (7) ◽  
Author(s):  
Maziar Aghvami ◽  
V. H. Barocas ◽  
E. A. Sander
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Mechanical Stimulation ◽  
Collagen Gel ◽  
Theoretical Models ◽  
Isometric Tension ◽  
Collagen Gels ◽  
Ecm Remodeling ◽  
Engineered Tissues ◽  
Mechanical Models

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.

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