Tissue engineering scaffolds are used extensively as three-dimensional analogs of the extracellular matrix (ECM). Collagen-glycosaminoglycan (CG) scaffolds have long been utilized as ECM analogs for the regeneration of skin and are currently being considered for the regeneration of nerve, conjunctiva, and a host or orthopedic tissues. Recently a series of CG scaffolds with a uniform pore microstructure has been developed with a range of sizes of equiaxed pores. Experimental characterization and theoretical modeling techniques have been used to describe the pore microstructure, specific surface area, tensile and compressive mechanical properties, cell attachment, and permeability of these variants. Here we describe the fabrication, and characterization, and modeling of a series of CG and mineralized CG scaffolds. We then discuss their use in vivo to induce tissue regeneration following injury and in vitro as standardized 3D materials to study the influence of microstructural and mechanical features on cell behaviors such as motility and contraction. (C) 2007 Elsevier B.V. All rights reserved.