Simulated remodeling of loaded collagen networks via strain-dependent enzymatic degradation and constant-rate fiber growth

Abstract

Recent work has demonstrated that enzymatic degradation of collagen fibers exhibits strain-dependent kinetics. Conceptualizing how the strain dependence affects remodeling of collagenous tissues is vital to our understanding of collagen management in native and bioengineered tissues. As a first step towards this goal, the current study puts forward a multiscale model for enzymatic degradation and remodeling of collagen networks for two sample geometries we routinely use in experiments as model tissues. The multiscale model, driven by microstructural data from an enzymatic decay experiment, includes an exponential strain-dependent kinetic relation for degradation and constant growth. For a dogbone sample under uniaxial load, the model predicted that the distribution of fiber diameters would spread over the course of degradation because of variation in individual fiber load. In a cross-shaped sample, the central region, which experiences smaller, more isotropic loads, showed more decay and less spread in fiber diameter compared to the arms. There was also a slight shift in average orientation in different regions of the cruciform.

Cell–matrix interaction during strain-dependent remodelling of simulated collagen networks

“…collagen fibres. The fibres were assigned an initial radius of 50 nm and stiffness of 79 MPa [34]. The fibre volume fraction of the RVEs was 1.2 + 0.07%.…”

“…The values of the constants k 1 and k 2 were obtained previously by fitting the experimental data of [32]. Hadi et al [34] found k 1 to be 1.05 Â 10 23 nm s 21 and k 2 to be 0.83. The obtained values are for a specific in vitro case of collagen degradation by bacterial collagenase.…”

Mathematical model of chronic pancreatitis

“…Fibrotic diseases are characterized by excessive scarring due to excessive production and deposition of ECM and disruption of normal healthy protein cross-linking. MMP disrupts collagen cross-linking and increases scarring in cases of excessive collagen concentrations (44,45). We accordingly represent the state of the scar by the equation…”

Modeling the impact of scaffold architecture and mechanical loading on collagen turnover in engineered cardiovascular tissues

“…A strain rate of 100 % strain/min is used ated on the mechanical data of the statically cultured isotropic and anisotropic constructs. The parameter k 3 refers to the degradation rate in absence of strain evaluated by Hadi et al (2012) on the basis of the experiments of Bhole et al (2009). Parameters k 4 and k 5 , describing the collagen degradation, were estimated using the experimental mechanical data of the biaxial isotropic statically loaded constructs and uniaxial cyclically loaded constructs, with strain applied along the scaffold fibers.…”

“…The degradation of collagen fibers happens according to strain-dependent kinetics. When strain is applied to a collagen gel, the collagen fibers that are oriented in the direction of the strain will degrade slower than the collagen fibers in all the other directions (Bhole et al 2009;Hadi et al 2012).…”