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Research Papers

Mechanical Behavior of Collagen-Fibrin Co-Gels Reflects Transition From Series to Parallel Interactions With Increasing Collagen Content

[+] Author and Article Information
Victor K. Lai

 Department of Chemical Engineering and Materials Science, University of Minnesota – Twin Cities, 421 Washington Ave SE, Minneapolis, MN 55455

Spencer P. Lake, Christina R. Frey

 Department of Biomedical Engineering, University of Minnesota – Twin Cities, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455

Robert T. Tranquillo

 Department of Chemical Engineering and Materials Science, University of Minnesota – Twin Cities, 421 Washington Ave SE, Minneapolis, MN 55455;  Department of Biomedical Engineering, University of Minnesota – Twin Cities, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455

Victor H. Barocas1

 Department of Biomedical Engineering, University of Minnesota – Twin Cities, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455baroc001@umn.edu.

1

Corresponding author: Victor H. Barocas, Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455.

J Biomech Eng 134(1), 011004 (Feb 09, 2012) (9 pages) doi:10.1115/1.4005544 History: Received August 29, 2011; Revised December 14, 2011; Posted January 23, 2012; Published February 08, 2012; Online February 09, 2012

Fibrin and collagen, biopolymers occurring naturally in the body, are biomaterials commonly-used as scaffolds for tissue engineering. How collagen and fibrin interact to confer macroscopic mechanical properties in collagen-fibrin composite systems remains poorly understood. In this study, we formulated collagen-fibrin co-gels at different collagen-to-fibrin ratios to observe changes in the overall mechanical behavior and microstructure. A modeling framework of a two-network system was developed by modifying our micro-scale model, considering two forms of interaction between the networks: (a) two interpenetrating but noninteracting networks (“parallel”), and (b) a single network consisting of randomly alternating collagen and fibrin fibrils (“series”). Mechanical testing of our gels show that collagen-fibrin co-gels exhibit intermediate properties (UTS, strain at failure, tangent modulus) compared to those of pure collagen and fibrin. The comparison with model predictions show that the parallel and series model cases provide upper and lower bounds, respectively, for the experimental data, suggesting that a combination of such interactions exists between the collagen and fibrin in co-gels. A transition from the series model to the parallel model occurs with increasing collagen content, with the series model best describing predominantly fibrin co-gels, and the parallel model best describing predominantly collagen co-gels.

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Copyright © 2012 by American Society of Mechanical Engineers
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Figures

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Figure 1

(a) Image showing the mechanical testing setup for collagen-fibrin rings, taken during prestrain. A mirror (to the right of the dotted line) is used to visualize the gel in the 1-3 plane. Dimensions of the gels are measured from these images to calculate the initial area, which is used to convert the force data to 1st Piola-Kirchhoff stress. (b) Representative stress-strain plot of a collagen-fibrin co-gel (41% C), showing how each parameter is determined.

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Figure 2

(a) Schematic representation of the parallel and series models of interactions in the two-network cases. (b) Model predictions of mechanical behavior in the networks generated using a single finite element with 8 Gauss points; each Gauss point is surrounded by a network RVE.

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Figure 3

Results from ELISA and hydroxyproline assays to quantify fibrin and collagen concentrations, respectively, in the gels. In general, no significant loss in either fibrin or collagen is observed in the co-gels. A significant loss in fibrin is observed in the pure fibrin gels; this loss is also macroscopically observed in the gel shrinkage and left-over liquid (containing unaggregated fibrinogen) when removed from the Teflon molds.

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Figure 4

SEM images taken at 30 000 × of pure fibrin and collagen gels (top) and collagen-fibrin co-gels (bottom). Collagen fibers can be differentiated from fibrin fibers by their characteristic banding pattern (arrows) on and the bundling of (*) the fibers. At higher collagen compositions (68% C, 83% C), wispier, weblike fibrin structures are observed. Scale bars = 1 μm; the scale bar in the 9% C image is representative for all co-gel images.

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Figure 5

Model fits to the experimental data to obtain material parameters A and B for fibrin and collagen, respectively. Collagen shows a much higher stiffness (in the A value) and a larger degree of nonlinearity (the B value) than fibrin. Error bars on the experimental data represent 95% CI, n ≥ 7 for both collagen and fibrin. Error bands on the model fits represent 95% CI, generated from four different networks for each.

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Figure 6

Model predictions from the parallel and series models compared with experiment (▪) across all seven compositions of the co-gels. In the parallel model, the dashed lines represent hypothetical stress-strain regions after the failure strain of pure collagen, above which the collagen network is expected to have catastrophically failed. In all cases, the parallel and series models provide upper and lower bounds to the experimental data. The series model shows better agreement to the experiment at low collagen content (9% C), while the parallel model shows better agreement at high collagen contents (68% C and 83% C). Error bars represent 95% CI; n ≥ 5 gels for experiments, n ≥ 6 networks for models.

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Figure 7

Material properties of co-gels from the experiment (▪, solid lines) compared with model predictions from the parallel (▴, dashed lines) and series (•, dotted lines) models. Parallel models reflect properties in the hypothetical region (defined in Fig. 6) beyond the failure strain of collagen. In general, both models are able to predict trends in the strain energy density, tangent modulus, and transition strain. The experimental data is bracketed by the parallel and series models in the UTS, strain energy density, and tangent modulus. Models predict the apparent Poisson’s ratio on the same order of magnitude as the experiment. Error bars represent 95% CI; n ≥ 5 gels for experiments, n ≥ 6 networks for models.

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Figure 8

Fibril stretch and fibril force distributions in the parallel and series models after the macroscopic stretch. In the parallel model, the collagen and fibrin networks exhibit similar fibril stretch distributions, however, forces in the collagen fibrils are much larger than those in the fibrin fibrils. In the series model, a much smaller difference between the collagen and fibrin fibril force distributions is observed, however, fibrin fibrils bear a larger proportion of macroscopic stretch. Distributions are of 54% C networks, taken from an RVE at a Gauss point after the final stretch step. The ▪ in the box plots represent the distribution mean and whiskers represent outliers within the interquartile range.

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