Collagen hydrogels with similar polymer content but different microstructure — A comparative analysis of mechanical response

Abstract

Understanding the mechanical properties of collagen hydrogels is essential for successful applications in tissue engineering and 3D cell culture. This study compares the mechanical behavior of two collagen hydrogel sheets with similar collagen content but different microstructures. One of the differences is that one gel is isotropic while the other has collagen fibers oriented towards the sheet’s plane. Experiments were performed at macro- (uniaxial tension in the sheet plane) and micro-length scale (AFM-based indentation perpendicular to the plane), and a discrete network model was developed to rationalize the observed differences. The experiments showed an order of magnitude difference in the uniaxial stiffness of the two gels. The softer gel exhibited near-incompressible behavior, while the stiffer gel showed a highly contractile response, with Poisson’s ratios around 8. Conversely, the apparent modulus from nano-indentation showed an opposite trend, with higher local stiffness for the gel that was softer in uniaxial tests. The computational model represents the material using a network of bi-linear connectors for the fibrous component and a compressible neo-Hookean material for the surrounding water-rich matrix, assumed to form due to interactions between collagen and water. Under the constraint of equal collagen content, model parameters were tuned to reproduce the observed response of both materials, considering the observed differences in fiber diameter. Importantly, the computations indicate that the difference in collagen orientation cannot explain the observed differences between the mechanical responses of the gels. Successful scaling between the two gels depends on the assumption that, due to their crimped initial state individual fibers primarily experience bending rather than tension when the material is stretched. Moreover, high tensile stretch of the fibers is shown to elicit large lateral contraction. Overall, the results demonstrate the wide range of mechanical properties displayed by hydrogels with similar collagen content, which can be rationalized using discrete models representative of their microstructure.