Based on significant progress in biotechnology, "Regenerative Medicine" is evolving as a new discipline that could significantly change current therapeutic approaches. Medicine, stem cell biology, tissue engineering, nanotechnology, genomic research, material sciences, as well as system- and process-engineering come together to answer fundamental problems of human disease, including trauma and aging. The long-term goal is to create a profound knowledge of individualized therapy originating from nonbiological organ replacement, through hybridized systems, to fully biological implants and finally to human regenerative systems in vivo. Two model tissues, including heart valves and liver tissue are discussed in the context of in vivo and in vitro regeneration technologies. Extracellular matrix regulates tissue differentiation in at least three ways, including the biochemical composition of the matrix constituents, the 3-D organization or architecture, and via mechanical forces mediated to the cells by the matrix. The in vivo extracellular matrix constitutes a biopolymer which potentially plays a permissive role for tissue differentiation.