This is a resubmitted PROGRAM PROJECT proposal following a thoughtful and supportive Review that has three separate research Projects that are supported by an Administrative Core and four technology Cores. The research Projects use state-of-the-art Tissue Engineering to address issues of articular cartilage repair. The entire proposal is centered on the theme of: Physical, Chemical and Biological Control of Tissue Engineered Cartilage. The approaches focus on cell-based technologies and are an outgrowth of over 20 years of experience in this investigative sector. All of the participants have previously interacted and the formation of this Program resulted from these formal and informal interactions. The long-term objective is to provide technologies that translate into clinically relevant protocols for cartilage repair. Thus, the integration of clinicians, cell and molecular scientists and engineers into a cohesive and interactive PROGRAM PROJECT team provides an effective and efficient mechanism for translating our scientific findings into clinical protocols. The three Projects are: I. Structured Microenvironment for Osteochondral Histogenesis;II. Biomimetic tissue-engineered articular cartilage repair and III. Total Joint Resurfacing. The four technology Cores provide cells (B), bioreactor capabilities (C), morphological processing and analysis (D), and Biomechanical analysis (E). The Administrative Core organizes the interactions between all Program participants and with outside Advisors who provide critical expertise to help guide the Program. Although each Project could stand alone, the open and frequent interactions of the participants adds substantial value both scientifically and clinically to the Program. Lastly, each of the technical Cores has both a service (to the Projects) and a research component that is relevant to the overall theme of the proposal. New text is indicated in the proposal by vertical lines in the margins. The Word software puts lines along paragraphs when even modest changes have been made.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Program Projects (P01)
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Application #
Study Section
Special Emphasis Panel (ZAR1-CHW-J (J1))
Program Officer
Wang, Fei
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Case Western Reserve University
Schools of Arts and Sciences
United States
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Whitney, G Adam; Kean, Thomas J; Fernandes, Russell J et al. (2018) Thyroxine Increases Collagen Type II Expression and Accumulation in Scaffold-Free Tissue-Engineered Articular Cartilage. Tissue Eng Part A 24:369-381
Chou, Chih-Ling; Rivera, Alexander L; Williams, Valencia et al. (2017) Micrometer scale guidance of mesenchymal stem cells to form structurally oriented large-scale tissue engineered cartilage. Acta Biomater 60:210-219
Whitney, G Adam; Jayaraman, Karthik; Dennis, James E et al. (2017) Scaffold-free cartilage subjected to frictional shear stress demonstrates damage by cracking and surface peeling. J Tissue Eng Regen Med 11:412-424
Kean, Thomas J; Mera, Hisashi; Whitney, G Adam et al. (2016) Disparate response of articular- and auricular-derived chondrocytes to oxygen tension. Connect Tissue Res 57:319-33
Whitney, G A; Mansour, J M; Dennis, J E (2015) Coefficient of Friction Patterns Can Identify Damage in Native and Engineered Cartilage Subjected to Frictional-Shear Stress. Ann Biomed Eng 43:2056-68
Chung, Chen-Yuan; Heebner, Joseph; Baskaran, Harihara et al. (2015) Ultrasound Elastography for Estimation of Regional Strain of Multilayered Hydrogels and Tissue-Engineered Cartilage. Ann Biomed Eng 43:2991-3003
Kean, Thomas J; Dennis, James E (2015) Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions. PLoS One 10:e0129961
Correa, D; Somoza, R A; Lin, P et al. (2015) Sequential exposure to fibroblast growth factors (FGF) 2, 9 and 18 enhances hMSC chondrogenic differentiation. Osteoarthritis Cartilage 23:443-53
Chung, Chen-Yuan; Mansour, Joseph M (2015) Determination of poroelastic properties of cartilage using constrained optimization coupled with finite element analysis. J Mech Behav Biomed Mater 42:10-8
Mansour, Joseph M; Gu, Di-Win Marine; Chung, Chen-Yuan et al. (2014) Towards the feasibility of using ultrasound to determine mechanical properties of tissues in a bioreactor. Ann Biomed Eng 42:2190-202

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