State diagrams of type I collagen for the rational design of biomimetic materials

The optimal approach to designing tissue engineering grafts and 3D cell culture materials is to mimic the architecture and composition of the extracellular matrix (ECM), which is predominantly comprised of type I collagen. However, while cells assemble collagen molecules into fibrils in vivo, it is rare for fibrils to form spontaneously in vitro. The physicochemical conditions for fibrillogenesis are still poorly understood, and their influence on the formation and properties of biomimetic materials remains elusive. Here, we establish state diagrams for type I collagen over a wide range of concentrations and temperatures. We show the emergence of fibrils in previously unreported regimes and demonstrate how these state diagrams guide the elaboration of new biomimetic materials. The state diagrams presented here will help in understanding the formation of collagen-based tissues, which are set to revolutionize the development of superior, more relevant biomaterials for tissue engineering and 3D cell culture.