關節軟骨一旦受損便難以做自我的修復，關節軟骨的治療面臨很大的挑戰。至今，臨床上的治療仍有很多問題存在，例如: 其修復的組織是纖維軟骨、來源的限制以及在體外培養時細胞的去分化等等。至今仍沒有一定的方式去治療受損的軟骨。乙醯葡萄糖胺及葡萄糖胺被用來治療退化性關節炎已長達30年的歷史，且被證明他們都具有軟骨保護的功能。但不論是口服亦或是於血管注射，其葡萄糖胺經身體循環系統擴散至關節是非常有限的。因此，本研究評估直接在關節內注射乙醯葡萄糖胺及玻尿酸於兔子膝關節骨軟骨(股骨內側髁)缺陷是否具有正向效益。
本研究主要分成兩部分: Part I: 探討直接於關節腔內注射乙醯葡萄糖胺對於骨軟骨缺陷(股骨內側髁)修復之影響。在術後一週後，關節內分別注射乙醯葡萄糖胺及生理食鹽水，每週施打兩次持續施打五週，並分別於第四週及第十二週犧牲。Part II:於本研究將基於結合具有功能性的聚乳酸聚甘醇酸(PLGA)的孔洞性支架，評估分別在關節施打乙醯葡萄糖胺、玻尿酸及乙醯葡萄糖胺結合玻尿酸三種關節補充液於骨軟骨缺陷再生之功效。乙醯葡萄糖胺在術後一週後每週施打兩次持續施打五週，而玻尿酸及乙醯葡萄糖胺結合玻尿酸組在術後一週後每週施打一次並持續施打三週，分別於第四週及第十二週犧牲。並進一步進行巨觀觀察、微型電腦斷層掃描、組織切片染色及組織免疫染色觀察等進行評估。
在直接注射乙醯葡萄胺的研究中，乙醯葡萄糖胺的注射有似透明軟骨的再生同時也促進骨頭的修復。結果顯示，乙醯葡萄糖胺組骨小樑的厚度(Tb.Th)有顯著性的提高，且於修復第十二週，乙醯葡萄糖胺組骨組織的體積(BV/TV)較控制組接近正常骨的比例 。組織切片染色分析顯示出施打乙醯葡萄糖胺組於十二週時有似透明軟骨的再生，較正常的葡萄胺聚糖表現、較好的軟骨排列以及Sox9的表現。
在關節中施打關節補充液結合聚乳酸聚甘醇酸支架研究中，於四週時，缺陷處完全的填滿新生的組織及未降解的支架，其施打乙醯葡萄糖胺、玻尿酸及乙醯葡萄糖胺結合玻尿酸組別都再生出較似透明軟骨的型態，而其評分不論是在第四週或第十二週也較純支架組有顯著性的差異。施打乙醯葡萄糖胺、玻尿酸及乙醯葡萄糖胺結合玻尿酸組其骨組織的體積(BV/TV)及骨小樑的厚度(Tb.Th) 相較於純支架組都有顯著性的提升不論是在第四週或第十二週。組織切片染色結果顯示出施打補充劑有似透明軟骨的再生及促進硬骨的修復，且於第四週及十二週其軟骨細胞都有Sox9的表現。
整體而言，在關節內注射乙醯葡萄糖胺對於軟骨有保護的功能及對骨軟骨的再生有正向的影響。再加上基於不具細胞的功能性孔洞支架結合在關節內注射乙醯葡萄糖胺、玻尿酸及乙醯葡萄糖胺結合玻尿酸，其結果顯示巨觀上有較好的結果、有似透明軟骨及硬骨的再生、有較好的軟骨排列及較多的醣胺多醣表現，特別是在注射乙醯葡萄糖胺組。

Repairing damaged articular cartilage is particularly challenging because of the limited self-repair ability of hyaline cartilage. Nowadays, several treatments are available for repairing damaged cartilage, but all of them still present numerous problems. For instance, the repaired tissues by autologous osteochondral plug (mosaicplasty) are turned into fibrocartilage, and limited source and even dedifferentiation of chondrocytes are the limitation for autologous chondrocyte implantation when chondrocytes are in vitro monolayer culture. So far, no defined conclusions for cartilage repair are reported. Glucosamine and N-acetyl-D-glucosamine (GlcNAc) have been used as supplements for the treatment of osteoarthritis for several years and have shown ability in cartilage protection. However, through either oral administration or intravenous injection (IV), the diffusion of glucosamine from the circulation into the joint is very inefficient. Therefore, this study examines the effect of direct intra-articular injection of GlcNAc and/or hyaluronan (HA) for repairing osteochondral defects in rabbit knee joints.
Part I of this study, the effect of intra-articular injection of GlcNAc for osteochondral defects in rabbits was investigated. Full-thickness osteochondral defect was created in the medial femoral condyle, then GlcNAc (G group) or normal saline were injected into joint capsulate twice a week starting 1 week postoperatively for a period of 5 weeks. Euthanasia was conducted at 4 weeks and 12 weeks after operation. Part II of this study, the efficacy of two supplementation solutions, GLcNAc and HA, combined with degradable functional Poly (lactide-co-glycolide) (PLGA) porous scaffold implantation in osteochondral defect regeneration was investigated. Three experiment groups of intra-articular injections include GlcNAc only (PLGA+G), clinical viscosupplementation HA only (PLGA+HA), and GlcNAc and HA combination (PLGA+G+HA), as well as a control group with PLGA implantation without any injection (PLGA). The HA and mixture solution groups were injected once a week starting 1 week postoperatively for a period of 3 weeks. GlcNAc was injected twice a week starting 1 week postoperatively for a period of 5 weeks. Euthanasia was conducted at 4 weeks and 12 weeks. The knees were evaluated by macroscopic evaluation, micro CT scanning, histology, and IHC staining.
Part I of this study, the results demonstrated that intra-articular administration of GlcNAc had better hyaline-like cartilage regeneration and promoted bone regeneration. The thickness of trabecular bone (Tb.Th) value of G group was significantly higher than control group and the bone volume/tissue volume (BV/TV) ratio of G group was near the BV/TV ratio of normal subchondral bone at 12 weeks. Histologic analysis revealed that the G group exhibited hyaline-like cartilage, better cartilage alignment compared with control group and the chondrocytes had Sox9 expression at 12 weeks.
Part II of this study, all of groups were completely filled with repaired tissue and PLGA scaffold at 4 weeks after operation. The PLGA+G, PLGA+HA and PLGA+G+HA groups had greater regeneration with nearly normal cartilage morphology that score of PLGA+G, PLGA+HA and PLGA+G+HA groups were significantly higher than PLGA group at 4 and 12 weeks. The BV/TV ratio and Tb.Th value were significantly higher in the PLGA+G, PLGA+HA and PLGA+G+HA groups compared with the PLGA group. The BV/TV ratio was significantly increased in the PLGA and PLGA+G+HA groups from 4 weeks through 12 weeks, and the Tb.Th value was significantly increased in all of the groups from 4 weeks through 12 weeks. Histologic analysis revealed that the PLGA+G, PLGA+HA and PLGA+G+HA groups exhibited hyaline-like cartilage and bone regeneration compared with PLGA group and the chondrocytes still had positive Sox9 expression at 12 weeks.
In summary, intra-articular injection of glucosamine promotes osteochondral regeneration and chondroprotective function. In addition, the acellular functional porous scaffold combined with intra-articular injecting supplementation solutions such as GlcNAc, HA, or GlcNAc with HA solution show great gross appearance, hyaline-like cartilage and bone regeneration, well collagen alignment and abundant amount of glucosaminoclycans (GAGs) expression, particularly in the injected PLGA+G group.

Adam, N. and P. Ghosh (2001). "Hyaluronan molecular weight and polydispersity in some commercial intra-articular injectable preparations and in synovial fluid." Inflammation Research 50(6): pp.294-299.
Akiyama, H., M. C. Chaboissier, J. F. Martin, A. Schedl and B. de Crombrugghe (2002). "The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6." Journal of Bone and Mineral Research 17: pp.S142-S142.
Arkill, K. P. and C. P. Winlove (2008). "Solute transport in the deep and calcified zones of articular cartilage." Osteoarthritis Cartilage 16(6): pp.708-714.
Azuma, K., T. Osaki, T. Tsuka, T. Imagawa, Y. Okamoto, Y. Takamori and S. Minami (2011). "Effects of Oral Glucosamine Hydrochloride Administration on Plasma Free Amino Acid Concentrations in Dogs." Marine Drugs 9(5): pp.712-718.
Billinghurst, R. C., L. Dahlberg, M. Ionescu, A. Reiner, R. Bourne, C. Rorabeck, P. Mitchell, J. Hambor, O. Diekmann, H. Tschesche, J. Chen, H. VanWart and A. R. Poole (1997). "Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage." Journal of Clinical Investigation 99(7): pp.1534-1545.
Buckwalter, J. A. and H. J. Mankin (1997). "Articular cartilage .1. Tissue design and chondrocyte-matrix interactions." Journal of Bone and Joint Surgery-American Volume 79A(4): pp.600-611.
Buckwalter, J. A., J. A. Martin, M. Olmstead, K. A. Athanasiou, M. P. Rosenwasser and V. C. Mow (2003). "Osteochondral repair of primate knee femoral and patellar articular surfaces: implications for preventing post-traumatic osteoarthritis." Iowa Orthop J 23: pp.66-74.
Burdick, J. A. and G. D. Prestwich (2011). "Hyaluronic Acid Hydrogels for Biomedical Applications." Advanced Materials 23(12): pp.H41-H56.
Chan, P. S., J. P. Caron, G. J. M. Rosa and M. W. Orth (2005). "Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E-2 in articular cartilage explants." Osteoarthritis and Cartilage 13(5): pp.387-394.
Chang, N. J., C. C. Lin, C. F. Li, D. A. Wang, N. Issariyaku and M. L. Yeh (2012). "The combined effects of continuous passive motion treatment and acellular PLGA implants on osteochondral regeneration in the rabbit." Biomaterials 33(11): pp.3153-3163.
Christoph Erggelet, B. R. M., Eike H Mrosek (2008). "Principles of Cartilage Repair." Springer.
Clegg, D. O., D. J. Reda, C. L. Harris, M. A. Klein, O. D. Jr, M. M. Hooper, J. D. Bradley, C. O. Bingham, M. H. Weisman, C. G. Jackson, N. E. Lane, J. J. Cush, L. W. Moreland, H. R. Schumacher, C. V. Oddis, F. Wolfe, J. A. Molitor, D. E. Yocum, T. J. Schnitzer, D. E. Furst, A. D. Sawitzke, H. Shi, K. D. Brandt, R. W. Moskowitz and H. J. Williams (2006). "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis." New England Journal of Medicine 354(8): pp.795-808.
d'Abusco, A. S., A. Corsi, M. G. Grillo, C. Cicione, V. Calamia, G. Panzini, A. Sansone, C. Giordano, L. Politi and R. Scandurra (2008). "Effects of intra-articular administration of glucosamine and a peptidyl-glucosamine derivative in a rabbit model of experimental osteoarthritis: a pilot study." Rheumatology International 28(5): pp.437-443.
de Haart, M., W. J. C. M. Marijnissen, G. J. V. M. van Osch and J. A. N. Verhaar (1999). "Optimization of chondrocyte expansion in culture - Effect of TGF beta-2, bFGF and L-ascorbic acid on bovine articular chondrocytes." Acta Orthop Scand 70(1): pp.55-61.
De Mattei, M., A. Pellati, M. Pasello, F. de Terlizzi, L. Massari, D. Gemmati and A. Caruso (2002). "High doses of glucosamine-HCl have detrimental effects on bovine articular cartilage explants cultured in vitro." Osteoarthritis and Cartilage 10(10): pp.816-825.
Derfoul, A., A. D. Miyoshi, D. E. Freeman and R. S. Tuan (2007). "Glucosamine promotes chondrogenic phenotype in both chondrocytes and mesenchymal stem cells and inhibits MMP-13 expression and matrix degradation." Osteoarthritis and Cartilage 15(6): pp.646-655.
Diaz-Gallego, L., J. G. Prieto, P. Coronel, L. E. Gamazo, M. Gimeno and A. I. Alvarez (2005). "Apoptosis and nitric oxide in an experimental model of osteoarthritis in rabbit after hyaluronic acid treatment." J Orthop Res 23(6): pp.1370-1376.
Dodge, G. R. and S. A. Jimenez (2003). "Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes." Osteoarthritis and Cartilage 11(6): pp.424-432.
Emans, P. J., L. W. van Rhijn, T. J. M. Welting, A. Cremers, N. Wijnands, F. Spaapen, J. W. Voncken and V. P. Shastri (2010). "Autologous engineering of cartilage." Proceedings of the National Academy of Sciences of the United States of America 107(8): pp.3418-3423.
Fenton, J. I., K. A. Chlebek-Brown, T. L. Peters, J. P. Caron and M. W. Orth (2000). "The effects of glucosamine derivatives on equine articular cartilage degradation in explant culture." Osteoarthritis and Cartilage 8(6): pp.444-451.
Frazza, E. J. and E. E. Schmitt (1970). "A New Synthetic Absorbable Suture - Orpl." Abstracts of Papers of the American Chemical Society: pp.5-&.
Gaulden, E. C. and W. C. Keating (1964). "The Effect of Intravenous N-Acetyl-D-Glucosamine on the Blood and Urine Sugar Concentrations of Normal Subjects." Metabolism-Clinical and Experimental 13: pp.466-472.
Ghosh, P. and D. Guidolin (2002). "Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent?" Semin Arthritis Rheum 32(1): pp.10-37.
Grimaud, E., D. Heymann and F. Redini (2002). "Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders." Cytokine Growth Factor Rev 13(3): pp.241-257.
Gwak, S. J. and B. S. Kim (2008). "Poly(lactic-co-glycolic acid) nanosphere as a vehicle for gene delivery to human cord blood-derived mesenchymal stem cells: comparison with polyethylenimine." Biotechnology Letters 30(7): pp.1177-1182.
Han, F., N. Ishiguro, T. Ito, T. Sakai and H. Iwata (1999). "Effects of sodium hyaluronate on experimental osteoarthritis in rabbit knee joints." Nagoya J Med Sci 62(3-4): pp.115-126.
Huang, L., Y. Y. Cheng, P. L. Koo, K. M. Lee, L. Qin, J. C. Y. Cheng and S. M. Kumta (2003). "The effect of hyaluronan on osteoblast proliferation and differentiation in rat calvarial-derived cell cultures." Journal of Biomedical Materials Research Part A 66A(4): pp.880-884.
Jain, R. A. (2000). "The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices." Biomaterials 21(23): pp.2475-2490.
Jiang, Y. Z., L. K. Chen, D. C. Zhu, G. R. Zhang, C. Guo, Y. Y. Qi and H. W. Ouyang (2010). "The Inductive Effect of Bone Morphogenetic Protein-4 on Chondral-Lineage Differentiation and In Situ Cartilage Repair." Tissue Engineering Part A 16(5): pp.1621-1632.
Kaps, C., S. Frauenschuh, M. Endres, J. Ringe, A. Haisch, J. Lauber, J. Buer, V. Krenn, T. Haeupl, G. R. Burmester and M. Sittinger (2006). "Gene expression profiling of human articular cartilage grafts generated by tissue engineering." Biomaterials 27(19): pp.3617-3630.
Karp, J. M., M. S. Shoichet and J. E. Davies (2003). "Bone formation on two-dimensional (DL-lactide-co-glycolide) (PLGA) films and three-dimensional PLGA tissue engineering scaffolds in vitro." Journal of Biomedical Materials Research Part A 64A(2): pp.388-396.
Kikuchi, T., H. Yamada and K. Fujikawa (2001). "Effects of high molecular weight hyaluronan on the distribution and movement of proteoglycan around chondrocytes cultured in alginate beads." Osteoarthritis and Cartilage 9(4): pp.351-356.
Kocher, M. S., R. Tucker, T. J. Ganley and J. M. Flynn (2006). "Management of osteochondritis dissecans of the knee - Current concepts review." American Journal of Sports Medicine 34(7): pp.1181-1191.
Kujawa, M. J. and A. I. Caplan (1986). "Hyaluronic acid bonded to cell-culture surfaces stimulates chondrogenesis in stage 24 limb mesenchyme cell cultures." Developmental Biology 114(2): pp.504-518.
Largo, R., M. A. Alvarez-Soria, I. Diez-Ortego, E. Calvo, O. Sanchez-Pernaute, J. Egido and G. Herrero-Beaumont (2003). "Glucosamine inhibits IL-1 beta-induced NF kappa B activation in human osteoarthritic chondrocytes." Osteoarthritis and Cartilage 11(4): pp.290-298.
Laverty, S., J. D. Sandy, C. Celeste, P. Vachon, J. F. Marier and A. H. K. Plaas (2005). "Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses." Arthritis and Rheumatism 52(1): pp.181-191.
Lee, P. B., Y. C. Kim, Y. J. Lim, C. J. Lee, W. S. Sim, C. W. Ha, S. I. Bin, K. B. Lim, S. S. Choi and S. C. Lee (2006). "Comparison between high and low molecular weight hyaluronates in knee osteoarthritis patients: Open-label, randomized, multicentre clinical trial." Journal of International Medical Research 34(1): pp.77-87.
Lu, J. M., X. Wang, C. Marin-Muller, H. Wang, P. H. Lin, Q. Yao and C. Chen (2009). "Current advances in research and clinical applications of PLGA-based nanotechnology." Expert Rev Mol Diagn 9(4): pp.325-341.
Maharjan, A. S., D. Pilling and R. H. Gomer (2011). "High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation." Plos One 6(10).
McCarty, M. F., A. L. Russell and M. P. Seed (2000). "Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis." Medical Hypotheses 54(5): pp.798-802.
Mendelson, A., E. Frank, C. Allred, E. Jones, M. Chen, W. L. Zhao and J. J. Mao (2011). "Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro." Faseb Journal 25(10): pp.3496-3504.
Miller, K. L. and D. O. Clegg (2011). "Glucosamine and Chondroitin Sulfate." Rheumatic Disease Clinics of North America 37(1): pp.103-+.
Miyakoshi, N., M. Kobayashi, K. Nozaka, K. Okada, Y. Shimada and E. Itoi (2005). "Effects of intraarticular administration of basic fibroblast growth factor with hyaluronic acid on osteochondral defects of the knee in rabbits." Arch Orthop Trauma Surg 125 (10): pp.683-692.
Nagaoka, I., M. Igarashi and K. Sakamoto (2012). "Biological activities of glucosamine and its related substances." Adv Food Nutr Res 65: pp.337-352.
Nakamura, T., S. Hitomi, S. Watanabe, Y. Shimizu, K. Jamshidi, S. H. Hyon and Y. Ikada (1989). "Bioabsorption of Polylactides with Different Molecular-Properties." Journal of Biomedical Materials Research 23(10): pp.1115-1130.
Neustadt, D. H. (2006). "Intra-articular injections for osteoarthritis of the knee." Cleveland Clinic Journal of Medicine 73(10): pp.897-+.
O'Driscoll, S. W., R. G. Marx, D. E. Beaton, Y. Miura, S. H. Gallay and J. S. Fitzsimmons (2001). "Validation of a simple histological-histochemical cartilage scoring system." Tissue Eng 7(3): pp.313-320.
Pan, J., X. Z. Zhou, W. Li, J. E. Novotny, S. B. Doty and L. Y. Wang (2009). "In Situ Measurement of Transport between Subchondral Bone and Articular Cartilage." Journal of Orthopaedic Research 27(10): pp.1347-1352.
Panseri, S., A. Russo, C. Cunha, A. Bondi, A. Di Martino, S. Patella and E. Kon (2012). "Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration." Knee Surgery Sports Traumatology Arthroscopy 20(6): pp.1182-1191.
Pavelka, K., J. Gatterova, M. Olejarova, S. Machacek, G. Giacovelli and L. C. Rovati (2002). "Glucosamine sulfate use and delay of progression of knee Osteoarthritis - A 3-year, randomized, placebo-controlled, double-blind study." Archives of Internal Medicine 162(18): pp.2113-2123.
Reginster, J. Y., R. Deroisy, L. C. Rovati, R. L. Lee, E. Lejeune, O. Bruyere, G. Giacovelli, Y. Henrotin, J. E. Dacre and C. Gossett (2001). "Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial." Lancet 357(9252): pp.251-256.
Rubin BR, T. J., Kongtawelert P, Pertusi RM, Forman MD, Gracy RW. (2001). "Oral polymeric N-acetyl-D-glucosamine and osteoarthritis." J Am Osteopath Assoc. 101(6): pp.339-344.
Sato, H., T. Takahashi, H. Ide, T. Fukushima, M. Tabata, F. Sekine, K. Kobayashi, M. Negishi and Y. Niwa (1988). "Antioxidant Activity of Synovial-Fluid, Hyaluronic-Acid, and 2 Subcomponents of Hyaluronic-Acid - Synovial-Fluid Scavenging Effect Is Enhanced in Rheumatoid-Arthritis Patients." Arthritis and Rheumatism 31(1): pp.63-71.
Sawitzke, A. D., H. Shi, M. F. Finco, D. D. Dunlop, C. L. Harris, N. G. Singer, J. D. Bradley, D. Silver, C. G. Jackson, N. E. Lane, C. V. Oddis, F. Wolfe, J. Lisse, D. E. Furst, C. O. Bingham, D. J. Reda, R. W. Moskowitz, H. J. Williams and D. O. Clegg (2010). "Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT." Annals of the Rheumatic Diseases 69(8): pp.1459-1464.
Schlichting, K., H. Schell, R. U. Kleemann, A. Schill, A. Weiler, G. N. Duda and D. R. Epari (2008). "Influence of Scaffold Stiffness on Subchondral Bone and Subsequent Cartilage Regeneration in an Ovine Model of Osteochondral Defect Healing." American Journal of Sports Medicine 36(12): pp.2379-2391.
Setnikar, I., C. Giacchetti and G. Zanolo (1986). "Pharmacokinetics of Glucosamine in the Dog and in Man." Arzneimittel-Forschung/Drug Research 36-1(4): pp.729-735.
Shea KG, J. J. J., Carey JL, Anderson AF, Oxford JT. (2012). "Osteochondritis Dissecans Knee Histology Studies Have Variable Findings and Theories of Etiology." Clin Orthop Relat Res.
Shikhman, A. R., D. Amiel, D. D'Lima, S. B. Hwang, C. Hu, A. Xu, S. Hashimoto, K. Kobayashi, T. Sasho and M. K. Lotz (2005). "Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis." Annals of the Rheumatic Diseases 64(1): pp.89-94.
Shikhman, A. R., D. C. Brinson, J. Valbracht and M. K. Lotz (2009). "Differential metabolic effects of glucosamine and N-acetylglucosamine in human articular chondrocytes." Osteoarthritis and Cartilage 17(8): pp.1022-1028.
Shikhman, A. R., K. Kuhn, N. Alaaeddine and M. Lotz (2001). "N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes." Journal of Immunology 166(8): pp.5155-5160.
Soltes, L., R. Mendichi, G. Kogan, J. Schiller, M. Stankovska and J. Arnhold (2006). "Degradative action of reactive oxygen species on hyaluronan." Biomacromolecules 7(3): pp.659-668.
Tamai, Y., K. Miyatake, Y. Okamoto, Y. Takamori, H. Sakamoto and S. Minami (2002). "Enhanced healing of cartilaginous injuries by glucosamine hydrochloride." Carbohydrate Polymers 48(4): pp.369-378.
Tamai, Y., K. Miyatake, Y. Okamoto, Y. Takamori, K. Sakamoto and S. Minami (2003). "Enhanced healing of cartilaginous injuries by N-acetyl-D-glucosamine and glucuronic acid." Carbohydrate Polymers 54(2): pp.251-262.
Temenoff, J. S. and A. G. Mikos (2000). "Review: tissue engineering for regeneration of articular cartilage." Biomaterials 21(5): pp.431-440.
Terry, D. E., K. Rees-Milton, C. Pruss, J. Hopwood, J. Carran and T. P. Anastassiades (2007). "Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO4)." Osteoarthritis Cartilage 15(8): pp.946-956.
Topol, E. J. (2004). "Failing the public health - Rofecoxib, Merck, and the FDA." New England Journal of Medicine 351(17): pp.1707-1709.
Uematsu, K., K. Hattori, Y. Ishimoto, J. Yamauchi, T. Habata, Y. Takakura, H. Ohgushi, T. Fukuchi and M. Sato (2005). "Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold." Biomaterials 26(20): pp.4273-4279.
Versier, G., F. Dubrana and F. A. Soc (2011). "Treatment of knee cartilage defect in 2010." Orthopaedics & Traumatology-Surgery & Research 97 (8): pp.S140-S153.
Wayne, J. S., C. L. McDowell, K. J. Shields and R. S. Tuan (2005). "In vivo response of polylactic acid-alginate scaffolds and bone marrow-derived cells for cartilage tissue engineering." Tissue Eng 11(5-6): pp.953-963.
Williams, G. M., E. F. Chan, M. M. Temple-Wong, W. C. Bae, K. Masuda, W. D. Bugbee and R. L. Sah (2010). "Shape, loading, and motion in the bioengineering design, fabrication, and testing of personalized synovial joints." Journal of Biomechanics 43(1): pp.156-165.
Xu, Z. C., W. J. Zhang, H. Li, L. Cui, L. Cen, G. D. Zhou, W. Liu and Y. L. Cao (2008). "Engineering of an elastic large muscular vessel wall with pulsatile stimulation in bioreactor." Biomaterials 29(10): pp.1464-1472.
Yang, C. X., M. L. Cao, H. Liu, Y. Q. He, J. Xu, Y. Du, Y. W. Liu, W. J. Wang, L. Cui, J. J. Hu and F. Gao(2012). "The High and Low Molecular Weight Forms of Hyaluronan Have Distinct Effects on CD44 Clustering." Journal of Biological Chemistry 287 (51): pp.43094-43107.
Yang, K. G. A., D. B. F. Saris, R. E. Geuze, Y. J. M. Van der Helm, M. H. P. Van Rijen, A. J. Verbout, W. J. A. Dhert and L. B. Creemers(2006). "Impact of expansion and redifferentiation conditions on chondrogenic capacity of cultured chondrocytes." Tissue Eng 12 (9): pp.2435-2447.
Yoon, H. Y., H. Koo, K. Y. Choi, I. C. Kwon, K. Choi, J. H. Park and K. Kim(2013). "Photo-crosslinked hyaluronic acid nanoparticles with improved stability for in vivo tumor-targeted drug delivery." Biomaterials 34(21): pp.5273-5280.
Zhou, P. H., S. Q. Liu and H. Peng (2008). "The effect of hyaluronic acid on IL-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis." J Orthop Res 26(12): pp.1643-1648.