Tissue engineering and regenerative medicine (TE/RM) is an evolving interdisciplinary field that integrates engineering with biology and medicine for the development of functional tissues and organs. Monitoring of tissues in vitro prior to implantation and assessment of tissues in vivo during development are both essential in order to optimize the regeneration of tissue and the restoration of organ function. Since direct visualization of developing tissues, i.e., tissue sampling via sacrifice or biopsy, is invasive and wasteful, one challenge in TE/RM is establishing non-invasive tools to monitor the development of the constructs in vitro and in vivo. In addition, visualization of the transitional region between the tissue implant and the surrounding tissues is critical to the establishment of the overall success of the procedure. MRI is increasingly being used in TE/RM to monitor the remodeling and regeneration of engineered tissues. Bioengineers can now generate spatial maps of MR relaxation times, diffusion coefficients, magnetization transfer ratios, and the shear modulus to monitor, for example, new bone growth for prosthetic therapy in TE/RM. We hypothesize that MR can be extended to monitor quantitatively the growth of engineered tissues including bone, fat, and cartilage. By its periodic application in vitro and in vivo MR can enable the much anticipated successes in TE/RM. Our preliminary data demonstrate that quantitative MR methods can be applied to characterize non-invasively the changes associated with adipogenesis, osteogenesis, and chondrogenesis in tissue-engineered MSC-based constructs. This in vitro work established that MR acquired data can be directly correlated with the underlying tissue composition and structure as measured by biochemical and histological techniques. Our long term goal is to extend these methods to assess the structure and function of developing, engineered tissues in vivo. In order to achieve this goal we have assembled an interdisciplinary team of imaging scientists, tissue engineers and clinicians. The proposed work forms a 5-year plan to establish useful clinical MR tools for the optimization of TE/RM specifically for chondrogenic tissues. Public Health Relevance Statement (provided by applicant): The objective of this study is to develop new techniques for monitoring engineered chondrogenic tissues using magnetic resonance imaging and magnetic resonance elastography. Magnetic resonance imaging provides three dimensional views of developing tissue at all stages of growth without the need to sacrifice the animal or to biopsy the tissue. Magnetic resonance elastography gives a direct measure of the strength and stiffness of regenerating tissue: critical information needed to guide the design of new methods of tissue engineering and to assess the success of tissue implants for restoring tissue damaged by disease, injury or cancer treatment.