Biomimetic collagen tissues: Collagenous tissue engineering and other applications

Collagen gels provide an in-vivo-like, 3D environment suitable for studying cell-matrix interactions during proto-tissue formation. Cell-seeded collagen gels, reconstituted under a variety of conditions, are remodeled by cell-driven compaction and consolidation. The remodeled gel, or tissue equivalent (TE), possesses properties dependent on the organization of collagen fibrils in the network, which, in turn, is controlled by several environmental factors, particularly mechanical constraints on the gel boundaries. Mechanical tests performed under a variety of conditions suggest that many different physical processes are involved in the gel's mechanical response. Network restructuring under nonuniform loading conditions leads to mechanical anisotropy and nonlinearity at large strain. Although similar in behavior, collagen-based TEs do not yet possess sufficient mechanical properties to replace native tissues. Efforts are underway to improve TE properties by controlling ECM composition and organization.