Abstract Blood clotting is the body’s natural reaction in wound healing and is also the cause of many pathologies. Fibrin – the main protein in the clotting process provides clots’ mechanical strength by forming a scaffold of complex fibrin fibers. Fibrin fibers exhibit high extensibility and primarily elastic properties under static loading, which differ from in vivo dynamic forces. In many biological materials, the mechanical response changes under repeated loading/unloading (cyclic loading). Using lateral force microscopy, we show fibrin fibers possess viscoelastic behavior and experience irreversible damage under cyclic loading. Cross-linking results in a more rigid structure with permanent damage occurring mostly at larger strains, which is corroborated by computational modeling of fibrin extension using a hyperelastic model. Molecular spectroscopy analysis with broadband coherent anti-Stokes Raman scattering spectroscopy in addition to molecular dynamic simulations allow identification of the source of damage, the unfolding pattern, and inter and intramolecular changes in fibrin. The results show partial recovery of protein’s secondary and tertiary structures under load, providing deeper understanding of fibrin’s unique behavior in wound healing or pathologies like stroke and embolism.
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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.
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- Award ID(s):
- 1911346
- PAR ID:
- 10468970
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Acta Biomaterialia
- Volume:
- 162
- Issue:
- C
- ISSN:
- 1742-7061
- Page Range / eLocation ID:
- 292 to 303
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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