Collagen-Agarose Co-Gels as a Model for Collagen-Matrix Interaction in Soft Tissue

Connective soft tissues have complex mechanical properties that are determined by their collagen fiber network and surrounding non-fibrillar material. The mechanical role of non-fibrillar material and the nature of its interaction with the collagen network remain poorly understood, in part because of the lack of a simple experimental model system to examine and quantify these properties. The development of a simple but representational experimental system will allow for greater insight into the interaction between fibers and the non-fibrillar matrix. Reconstituted Type I collagen gels are an attractive model tissue for exploring micro- and macroscale relationships between constituents (e.g., [1–2]), but standard collagen gels lack the non-fibrillar components (i.e., proteoglycan, minor collagens, etc.) present in native tissue. A recent study [3] added low quantities of agarose to collagen gels, which dramatically increased the shear storage modulus with minimal changes to the collagen fiber network. In this study, we suggest that collagen-agarose co-gels can serve as a model system to investigate the mechanical role of non-fibrillar ECM. Even though agarose is relatively compliant at low concentrations, and collagen fibers are very stiff in tension, we hypothesized that the presence of agarose in co-gels would have a pronounced effect on structural response and mechanical behavior in tensile loading. Therefore, the objective of this study was to examine the properties of collagen-agarose co-gels to understand better the nature of, and the relationships between, the collagen fiber network and non-fibrillar matrix of simplified tissue analogs.