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Multiscale Mechanical Characterization of Fibrin Gels
The extracellular matrix (ECM) is a dynamic network of biomolecules that provides tissues with structural organization and regulates cellular behavior. Cells remodel the ECM at the micro- (1-10 μm) and mesoscales (10-1000 μm) in response to mechanical and biochemical stimuli, ultimately changing the macroscale (1-10 mm) mechanical properties of tissues. Thus, understanding the relationships between the macroscale tissue mechanics and the mesoscale ECM structure is needed across biomedical applications, for example, in the design of scaffolds that provide a transient matrix to support and promote wound healing and regeneration after injury. Common scaffolding materials include biopolymers like collagen and fibrin.
Fibrin is a naturally occurring protein that forms a temporary structure for remodeling during wound healing. It is also a common tissue engineering scaffold because its structural properties can be controlled. Here, we present a strategy to quantify the multiscale mechanics of fibrin gels by measuring both the macroscale stress-strain response and the deformation of the mesoscale fibrin network structure during uniaxial tensile tests. This information can be used to inform multiscale computational models that predict how alterations of the microstructural properties of the ECM influence macroscale mechanical properties and, reciprocally, how macroscale deformations lead to changes in the structure and organization of the cellular microenvironment.
While homogeneous scaffolds are commonly used to support tissue constructs, these do not accurately recapitulate the organization of the ECM in vivo, particularly, near interfacial tissue boundaries where ECM composition, organization, and density can differ drastically (e.g. tumor and the surrounding stroma, wound surrounded by healthy tissue). To address this gap, we developed an in vitro model using heterogeneous fibrin gels to recapitulate an interfacial ECM boundary. We first informed a computational model with the experimentally-determined stress-strain response and organization of homogeneous fibrin gels. The model was then used to predict the non-uniform stress and strain of a heterogeneous fibrin gel under uniaxial tension. The simulations were compared with experimentally measured macroscale stress and strain of heterogeneous fibrin gels, confirming the predictive capabilities of the computational model. The strategies proposed here can be extended to characterize the multiscale mechanics of other biological materials and improve scaffold design, including complex interfacial ECM boundaries between tissues.