The overall goal of this researches to design strategies for cartilage repair. Specifically, we will create novel materials derived from glucosamine and determine the mechanism of glucosamine action on chondrocytes and bone marrow derived stem cells. Glucosamine has had a long history in clinical treatment of cartilage degeneration. Unfortunately there has been conflicting validation of efficacy in vitro and little understanding of glucosamine's mechanism of action. Some researchers have hypothesized that glucosamine functions to directly increase cartilage polysaccharide synthesis. The expertise of a glycobiologist is critical to finally understanding glucosamine activity on cartilage. Our preliminary data and coPI expertise demonstrates that glucosamine functions by O-Glc-NAc protein modification which in turn regulates numerous cell activities to increase matrix production. We have also demonstrated increased cartilage extracellular matrix deposition in hydrogels when engineering cartilage from chondrocytes and mesenchymal stem cells (MSCs) in the presence of glucosamine. Results of this study will allow us to definitively provide the mechanism of glucosamine action on cartilage growth and design appropriate repair strategies. This proposal is both hypothesis driven and design driven. We hypothesize that glucosamine enters the metabolic hexosamine pathway in cells that supports O-GlcNAc-mediated cell responses to improve new cartilage formation instead of being directly incorporated into glycosaminoglycan synthesis as previously hypothesized by researchers. In the design portion of the proposal we will investigate chondrocyte and MSC response to glucosamine in hydrogel tissue engineering systems. Furthermore, we will develop novel materials derived from glucosamine so that the molecule can be readily released from a biomaterial scaffold for in vivo delivery. The following specific aims will address these research topics.
Specific aim 1. Evaluate glucosamine activity on cartilage tissue engineering 1A: Determine glucosamine influence on cartilage tissue formation by chondrocytes and MSCs. 1B: Identify specific biochemical pathways responsible for cellular responses to glucosamine.
Specific aim 2. Synthesize a polymeric glucosamine for incorporation into 3D scaffolds for cartilage engineering. . ? ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
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Johns Hopkins University
Biomedical Engineering
Schools of Medicine
United States
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Yang, Jessica P; Anderson, Amy E; McCartney, Annemarie et al. (2017) Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells. Tissue Eng Part A 23:253-262
Kim, Chaekyu; Shores, Lucas; Guo, Qiongyu et al. (2016) Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-d-Glucosamine Promote Cartilage Regeneration. Tissue Eng Part A 22:689-97
Kim, Chaekyu; Jeon, Ok Hee; Kim, Do Hun et al. (2016) Local delivery of a carbohydrate analog for reducing arthritic inflammation and rebuilding cartilage. Biomaterials 83:93-101
Singh, Anirudha; Li, Peter; Beachley, Vince et al. (2015) A hyaluronic acid-binding contact lens with enhanced water retention. Cont Lens Anterior Eye 38:79-84
Beachley, Vince Z; Wolf, Matthew T; Sadtler, Kaitlyn et al. (2015) Tissue matrix arrays for high-throughput screening and systems analysis of cell function. Nat Methods 12:1197-204
Corvelli, Michael; Che, Bernadette; Saeui, Christopher et al. (2015) Biodynamic performance of hyaluronic acid versus synovial fluid of the knee in osteoarthritis. Methods 84:90-8
Singh, Anirudha; Corvelli, Michael; Unterman, Shimon A et al. (2014) Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid. Nat Mater 13:988-95
Gibson, Matthew; Li, Hanwei; Coburn, Jeannine et al. (2014) Intra-articular delivery of glucosamine for treatment of experimental osteoarthritis created by a medial meniscectomy in a rat model. J Orthop Res 32:302-9
Coburn, Jeannine M; Wo, Luccie; Bernstein, Nicholas et al. (2013) Short-chain fatty acid-modified hexosamine for tissue-engineering osteoarthritic cartilage. Tissue Eng Part A 19:2035-44
Sharma, Blanka; Fermanian, Sara; Gibson, Matthew et al. (2013) Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med 5:167ra6

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