The aim of this NIBIB P41 Biomedical Technology Resource Center (BTRC) proposal is to establish a Center for Multimodal Evaluation of Engineered Cartilage at Case Western Reserve University (CWRU). Engineered tissues are close to entering clinical practice, and have the potential to replace a variety of prosthetic devices. The use of cells in engineered tissue introduces considerable variability into the process, resulting in unpredictable quality of tissue engineered (TE) constructs. This is a severe and limiting problem, as these constructs must ultimately replace all the essential functions of their target tissue when implanted. Failure can occur in many modes, and multiple minor deficiencies can have cumulative effects. All available information suggests that if a TE construct fails in any one mode, then it has not yet reached implantability. This has led us to conclude that robust, validated, and ideally non-destructive / non-invasive tools for continuous monitoring and assessment of the entire TE process, and of its end-product, are essential to ensure the production of implantable cartilage. Monitoring and assessment cannot focus on just one aspect of the TE process; rather, we must address the biological, biochemical and biomechanical aspects of the process in parallel. Similar problems, and thus needs, also affect our global network of colleagues engaged in cartilage TE. Hence, there is a need to establish technology and protocols for multimodal evaluation of TE cartilage. The proposed Center will fill that need by becoming a platform for developing, testing, validating, and disseminating new methods of evaluating cartilage TE processes and products, and a broadly accessible resource for Collaborative and Service interactions. Our team incorporates the biological and engineering expertise of several departments at CWRU, and has collaborated for decades on cartilage TE. We have accumulated experience, expertise, and technology related to cartilage evaluation that is not available elsewhere in a like concentration. Four Technology Research and Development (TR&D) projects are proposed, which will: 1) develop imaging modalities to longitudinally track the state of cartilage tissue differentiation - development of a miRNA-based imaging system is a major component; 2) develop non-invasive methods to analyze cell differentiation based on modified cells as probes, and tools to predict the ECM composition based on matrix remodeling during tissue growth; 3) develop technologies to evaluate the endogenous and exogenous biochemical environment of the chondrogenesis process; and 4) develop methods for imaging-guided multiscale, multimodal mechanical evaluation of TE cartilage. Each TR&D will: i) develop and validate technologies in well-characterized systems; ii) apply the technology to TE constructs from our collaborators; iii) exhaustively analyze these constructs post-test using conventional methods; and iv) accrue a cross- disciplinary database of information on the performance of TE cartilage. This work will assist in the development of new TE strategies; despite the focus on cartilage, the concept of multimodal evaluation is fundamental for all types of tissue constructs, and the technology we will develop is versatile and extensible to other tissue types.
As cartilage degeneration is one of the leading causes of disability, the potential patient population which could be candidates for tissue engineered cartilage treatment is very large. Currently the quality of engineered cartilage is variable. There is a strong need to develop and improve many biological, biochemical, and biomechanical aspects of the engineering process to ultimately ensure clinical safety and efficacy. The evaluation tools we will develop at the Center will make major contributions toward improving tissue-engineered products.
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