Multiscale mechanical characterization and computational modeling of fibrin gels

Fibrin is a naturally occurring protein network that forms a temporary structure to enable remodeling during wound healing. It is also a common tissue engineering scaffold because the structural properties can be controlled. However, to fully characterize the wound healing process and improve the design of regenerative scaffolds, understanding fibrin mechanics at multiple scales is necessary. Here, we present a strategy to quantify both the macroscale (1-10 mm) stress-strain response and the deformation of the mesoscale (10-1000 µm) network structure during unidirectional tensile tests. The experimental data were then used to inform a computational model to accurately capture the mechanical response of fibrin gels. Simultaneous mechanical testing and confocal microscopy imaging of fluorophore-conjugated fibrin gels revealed up to an 88% decrease in volume coupled with increase in volume fraction in deformed gels, and non-affine fiber alignment in the direction of deformation. Combination of the computational model with finite element analysis enabled us to predict the strain fields that were observed experimentally within heterogenous fibrin gels with spatial variations in material properties. These strategies can be expanded to characterize and predict the macroscale mechanics and mesoscale network organization of other heterogeneous biological tissues and matrices. STATEMENT OF SIGNIFICANCE: Fibrin is a naturally-occurring scaffold that supports cellular growth and assembly of de novo tissue and has tunable material properties. Characterization of meso- and macro-scale mechanics of fibrin gel networks can advance understanding of the wound healing process and impact future tissue engineering approaches. Using structural and mechanical characteristics of fibrin gels, a theoretical and computational model that can predict multiscale fibrin network mechanics was developed. These data and model can be used to design gels with tunable properties.