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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