軟骨再生始終是臨床的一項挑戰，近年來許多研究致力於以組織工程的方式來解決修復軟骨缺損這項問題。雖然水膠在軟骨組織工程領域中已被研究多年，但其在臨床上的應用仍存在著侷限性，包含機械性能、生物相容性，甚至是促進幹細胞分化等問題。這些因素都對於調控細胞在水膠支架之中的增殖扮演著重要的角色。而許多金屬離子對人體內的組織修復有著至關重要的作用，尤其是可以減緩軟骨病變的鎂離子，以及對關節軟骨有保護效果的鋅離子。故本研究旨在使用以甲基丙烯酸化殼聚醣光交聯水膠為基底，並在合成階段分別加入二價金屬陽離子鎂與鋅，形成離子水膠，並結合髕骨下脂肪墊間質幹細胞作為細胞來源，以完整軟骨組織工程的架構。
本研究成功製造出一摻有鎂離子和鋅離子的水膠支架，各組皆具備均勻緻密的多孔結構，伴隨著高吸水能力且無發生顯著的體積變化。鎂離子與鋅離子水膠分別在機械性質測試的低應變與高應變區，比純光固化水膠具有更突出的抗壓縮能力；不僅生物相容性良好、對幹細胞有促進增長的能力，較高濃度的離子水膠更使得軟骨細胞與幹細胞有著顯著的胞外基質分泌。如上所述，本研究所製備之摻有鎂離子和鋅離子的水膠，在較高的離子濃度下，有望成為符合組織工程概念之一創新的促軟骨再生理想支架。

Cartilage regeneration has consistently been a clinical challenge. In recent years, numerous studies have focused on addressing cartilage defect repair through tissue engineering approaches. Although multiple extensive studies on cartilage tissue engineering, hydrogels face clinical limitations such as mechanical properties, biocompatibility, and stem cell differentiation. These factors are crucial in controlling cell proliferation within scaffolds. Many metal ions are vital for tissue repair in the body, particularly magnesium ions and zinc ions. The former mitigates cartilage degeneration, and the latter have protective effects on articular cartilage. Therefore, this study aims to use methacrylated chitosan photo-crosslinked hydrogel as a base, incorporating divalent metal cations, magnesium and zinc, to form ion-incorporating hydrogels. Additionally, infrapatellar fat pad-derived mesenchymal stem cells were used to complete the cartilage tissue engineering framework.
Hydrogel scaffolds incorporating magnesium and zinc ions were successfully fabricated in this study. Each group demonstrated a uniform, dense, porous structure with a high swelling ratio without noticeable volumetric changes. Hydrogels with magnesium and zinc ions exhibited superior compressive modulus in the low and high strain stages of compression testing compared to a pure photo-crosslinked hydrogel. They also showed excellent biocompatibility and promoted stem cell growth. Moreover, they significantly enhanced extracellular matrix secretion by cells at higher ion concentrations. In conclusion, the hydrogels incorporating magnesium and zinc ions show promise as an innovative scaffold for promoting cartilage regeneration in alignment with tissue engineering concepts, particularly at higher ion concentrations.

[1] Mescher Anthony L, "Junqueira's Basic Histology: Text & Atlas (IE)," McGraw Hill, 2019, ISBN: 9781266021398.
[2] Poole A. Robin, Kojima Toshi, Yasuda Tadashi, Mwale Fackson, Kobayashi Masahiko, and Laverty Sheila, "Composition and Structure of Articular Cartilage: A Template for Tissue Repair," Clinical Orthopaedics and Related Research®, vol. 391, pp. S26-S33, 2001, doi: 10.1097/00003086-200110001-00004
[3] Wei W. Y. and Dai H. L., "Articular cartilage and osteochondral tissue engineering techniques: Recent advances and challenges," Bioactive Materials, vol. 6, no. 12, pp. 4830-4855, Dec 2021, doi: 10.1016/j.bioactmat.2021.05.011.
[4] Ulrich-Vinther Michael, Maloney Michael D., Schwarz Edward M., Rosier Randy, and O'Keefe Regis J., "Articular Cartilage Biology," JAAOS - Journal of the American Academy of Orthopaedic Surgeons, vol. 11, no. 6, pp. 421-430, 2003.
[5] Bhosale Abhijit M. and Richardson James B., "Articular cartilage: structure, injuries and review of management," British Medical Bulletin, vol. 87, no. 1, pp. 77-95, 2008, doi: 10.1093/bmb/ldn025.
[6] Akkiraju Hemanth and Nohe Anja, "Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration," Journal of Developmental Biology, vol. 3, no. 4, pp. 177-192, 2015, doi: 10.3390/jdb3040177.
[7] Xu W. C., Zhu J., Hu J. W., and Xiao L., "Engineering the biomechanical microenvironment of chondrocytes towards articular cartilage tissue engineering," Life Sciences, vol. 309, Nov 15 2022, doi: 10.1016/j.lfs.2022.121043.
[8] Chen M. H., Jiang Z. Y., Zou X. Y., You X. B., Cai Z., and Huang J. M., "Advancements in tissue engineering for articular cartilage regeneration," Heliyon, vol. 10, no. 3, Feb 15 2024, doi: 10.1016/j.heliyon.2024.e25400.
[9] Baumann Charles A., Hinckel Betina B., Bozynski Chantelle C., and Farr Jack, "Articular Cartilage: Structure and Restoration," Joint Preservation of the Knee: A Clinical Casebook, A. B. Yanke and B. J. Cole Eds. Springer, Cham, 2019, pp. 3-24, doi: 10.1007/978-3-030-01491-9_1.
[10] Pearle A. D., Warren R. F., and Rodeo S. A., "Basic science of articular cartilage and osteoarthritis," Clinics in Sports Medicine, vol. 24, no. 1, pp. 1-12, Jan 2005, doi: 10.1016/j.csm.2004.08.007.
[11] Cohen N. P., Foster R. J., and Mow V. C., "Composition and Dynamics of Articular Cartilage: Structure, Function, and Maintaining Healthy State," Journal of Orthopaedic & Sports Physical Therapy, vol. 28, no. 4, pp. 203-215, 1998, doi: 10.2519/jospt.1998.28.4.203.
[12] Youn I., Choi J. B., Cao L., Setton L. A., and Guilak F., "Zonal variations in the three-dimensional morphology of the chondron measured in situ using confocal microscopy," Osteoarthritis Cartilage, vol. 14, no. 9, pp. 889-97, Sep 2006, doi: 10.1016/j.joca.2006.02.017.
[13] Sophia Fox A. J., Bedi A., and Rodeo S. A., "The basic science of articular cartilage: structure, composition, and function," Sports Health, vol. 1, no. 6, pp. 461-8, Nov 2009, doi: 10.1177/1941738109350438.
[14] Hoemann C. D., Lafantaisie-Favreau C. H., Lascau-Coman V., Chen G., and Guzman-Morales J., "The cartilage-bone interface," Journal of Knee Surgery, vol. 25, no. 2, pp. 85-97, May 2012, doi: 10.1055/s-0032-1319782.
[15] Norrdin R., Kawcak C., Capwell B., and McIlwraith C., "Calcified cartilage morphometry and its relation to subchondral bone remodeling in equine arthrosis. Bone," Bone, vol. 24, no. 2, pp. 109-114, 1999, doi: 10.1016/s8756-3282(98)00157-4.
[16] Hwang J., Kyubwa E. M., Bae W. C., Bugbee W. D., Masuda K., and Sah R. L., "In Vitro Calcification of Immature Bovine Articular Cartilage: Formation of a Functional Zone of Calcified Cartilage," Cartilage, vol. 1, no. 4, pp. 287-297, Oct 1 2010, doi: 10.1177/1947603510369552.
[17] Becerra J., Andrades J. A., Guerado E., Zamora-Navas P., Lopez-Puertas J. M., and Reddi A. H., "Articular cartilage: structure and regeneration," Tissue Engineering, Part B: Reviews, vol. 16, no. 6, pp. 617-27, Dec 2010, doi: 10.1089/ten.TEB.2010.0191.
[18] Kwon H., Brown W. E., Lee C. A., Wang D. A., Paschos N., Hu J. C. et al., "Surgical and tissue engineering strategies for articular cartilage and meniscus repair," Nature Reviews Rheumatology, vol. 15, no. 9, pp. 550-570, Sep 2019, doi: 10.1038/s41584-019-0255-1.
[19] Lories R. J. and Luyten F. P., "The bone-cartilage unit in osteoarthritis," Nature Reviews Rheumatology, vol. 7, no. 1, pp. 43-49, Jan 2011, doi: 10.1038/nrrheum.2010.197.
[20] Mankin H. J., "The response of articular cartilage to mechanical injury," The Journal of Bone and Joint Surgery, vol. 64, no. 3, pp. 460-6, Mar 1982, doi: 10.2106/00004623-198264030-00022.
[21] Zheng L. L., Zhang Z. J., Sheng P. Y., and Mobasheri A., "The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis," Ageing Research Reviews, vol. 66, Mar 2021, doi: 10.1016/j.arr.2020.101249.
[22] Hunter D. J., Schofield D., and Callander E., "The individual and socioeconomic impact of osteoarthritis," Nature Reviews Rheumatology, vol. 10, no. 7, pp. 437-441, Jul 2014, doi: 10.1038/nrrheum.2014.44.
[23] Long H. B., Liu Q., Yin H. Y., Wang K., Diao N. C., Zhang Y. Q. et al., "Prevalence Trends of Site-Specific Osteoarthritis From 1990 to 2019: Findings From the Global Burden of Disease Study 2019," Arthritis Rheumatol, vol. 74, no. 7, pp. 1172-1183, Jul 2022, doi: 10.1002/art.42089.
[24] Newman Alan P., "Articular Cartilage Repair," The American Journal of Sports Medicine, vol. 26, no. 2, pp. 309-324, 1998, doi: 10.1177/03635465980260022701.
[25] Bedi Asheesh, Feeley Brian T., and Williams Riley J. III, "Management of Articular Cartilage Defects of the Knee," Journal of Bone and Joint Surgery, vol. 92, no. 4, pp. 994-1009, 2010, doi: 10.2106/jbjs.I.00895.
[26] Gillogly. Scott D., Voight. Michael, and Blackburn. Tab, "Treatment of Articular Cartilage Defects of theKnee With Autologous Chondrocyte Implantation," Journal of Orthopaedic & Sports Physical Therapy, vol. 28, no. 4, pp. 241-251, 1998, doi: 10.2519/jospt.1998.28.4.241.
[27] Zheng M. H., Willers C., Kirilak L., Yates P., Xu J. K., Wood D. et al., "Matrix-induced autologous chondrocyte implantation (MACI®):: Biological and histological assessment," Tissue Engineering, vol. 13, no. 4, pp. 737-746, Apr 2007, doi: 10.1089/ten.2006.0246.
[28] Darling E. M. and Athanasiou K. A., "Rapid phenotypic changes in passaged articular chondrocyte subpopulations," Journal of Orthopaedic Research, vol. 23, no. 2, pp. 425-432, Mar 2005, doi: 10.1016/j.orthres.2004.08.008.
[29] Roseti L., Desando G., Cavallo C., Petretta M., and Grigolo B., "Articular Cartilage Regeneration in Osteoarthritis," Cells, vol. 8, no. 11, Oct 23 2019, doi: 10.3390/cells8111305.
[30] Makris E. A., Gomoll A. H., Malizos K. N., Hu J. C., and Athanasiou K. A., "Repair and tissue engineering techniques for articular cartilage," Nature Reviews Rheumatology, vol. 11, no. 1, pp. 21-34, Jan 2015, doi: 10.1038/nrrheum.2014.157.
[31] Liu Y., Zhou G. D., and Cao Y. L., "Recent Progress in Cartilage Tissue Engineering-Our Experience and Future Directions," Engineering, vol. 3, no. 1, pp. 28-35, Feb 2017, doi: 10.1016/J.Eng.2017.01.010.
[32] Tevlin R., Walmsley G. G., Marecic O., Hu M. S., Wan D. C., and Longaker M. T., "Stem and progenitor cells: advancing bone tissue engineering," Drug Delivery and Translational Research, vol. 6, no. 2, pp. 159-173, Apr 2016, doi: 10.1007/s13346-015-0235-1.
[33] Zhang L., Hu J., and Athanasiou K. A., "The role of tissue engineering in articular cartilage repair and regeneration," Critical Reviews in Biomedical Engineering, vol. 37, no. 1-2, pp. 1-57, 2009, doi: 10.1615/critrevbiomedeng.v37.i1-2.10.
[34] Wang M., Wu Y., Li G., Lin Q., Zhang W., Liu H. et al., "Articular cartilage repair biomaterials: strategies and applications," Materials Today Bio, vol. 24, p. 100948, Feb 2024, doi: 10.1016/j.mtbio.2024.100948.
[35] Brodkin K. R., García A. J., and Levenston M. E., "Chondrocyte phenotypes on different extracellular matrix monolayers," Biomaterials, vol. 25, no. 28, pp. 5929-5938, Dec 2004, doi: 10.1016/j.biomaterials.2004.01.044.
[36] Ullah Imran, Subbarao Raghavendra Baregundi, and Rho Gyu Jin, "Human mesenchymal stem cells - current trends and future prospective," Bioscience Reports, vol. 35, no. 2, 2015, doi: 10.1042/bsr20150025.
[37] Hindle Paul, Khan Nusrat, Biant Leela, and Péault Bruno, "The Infrapatellar Fat Pad as a Source of Perivascular Stem Cells with Increased Chondrogenic Potential for Regenerative Medicine," Stem Cells Translational Medicine, vol. 6, no. 1, pp. 77-87, 2016, doi: 10.5966/sctm.2016-0040.
[38] Tanner K. E., "Bioactive composites for bone tissue engineering," Proceedings of The Institution of Mechanical Engineers Part H-Journal of Engineering in Medicine, vol. 224, no. H12, pp. 1359-1372, 2010, doi: 10.1243/09544119jeim823.
[39] Saekhor K., Udomsinprasert W., Honsawek S., and Tachaboonyakiat W., "Preparation of an injectable modified chitosan-based hydrogel approaching for bone tissue engineering," International Journal of Biological Macromolecules, vol. 123, pp. 167-173, Feb 15 2019, doi: 10.1016/j.ijbiomac.2018.11.041.
[40] Adhikari U., Rijal N. P., Khanal S., Pai D., Sankar J., and Bhattarai N., "Magnesium incorporated chitosan based scaffolds for tissue engineering applications," Bioactive Materials, vol. 1, no. 2, pp. 132-139, Dec 2016, doi: 10.1016/j.bioactmat.2016.11.003.
[41] Kaderli S., Boulocher C., Pillet E., Watrelot-Virieux D., Rougemont A. L., Roger T. et al., " International Journal of Pharmaceutics, vol. 483, no. 1-2, pp. 158-168, Apr 10 2015, doi: 10.1016/j.ijpharm.2015.01.052.
[42] Li H. J., Hu C., Yu H. J., and Chen C. Z., "Chitosan composite scaffolds for articular cartilage defect repair: a review," RSC Advances, vol. 8, no. 7, pp. 3736-3749, 2018, doi: 10.1039/c7ra11593h.
[43] Wang Wenqian, Meng Qiuyu, Li Qi, Liu Jinbao, Zhou Mo, Jin Zheng et al., "Chitosan Derivatives and Their Application in Biomedicine," International Journal of Molecular Sciences, vol. 21, no. 2, p. 487, 2020, doi: 10.3390%2Fijms21020487.
[44] Zanon Michael, Chiappone Annalisa, Garino Nadia, Canta Marta, Frascella Francesca, Hakkarainen Minna et al., "Microwave-assisted methacrylation of chitosan for 3D printable hydrogels in tissue engineering," Materials Advances, vol. 3, no. 1, pp. 514-525, 2022, doi: 10.1039/D1MA00765C.
[45] Taokaew Siriporn, Kaewkong Worasak, and Kriangkrai Worawut, "Recent Development of Functional Chitosan-Based Hydrogels for Pharmaceutical and Biomedical Applications," Gels, vol. 9, no. 4, p. 277, 2023, doi: 10.3390/gels9040277.
[46] Ma Jun, Yu Han, Zhang Xinyu, Xu Zhuoming, Hu Hanyin, Liu Jintao et al., "Dual-Targeted Metal Ion Network Hydrogel Scaffold for Promoting the Integrated Repair of Tendon–Bone Interfaces," ACS Applied Materials & Interfaces, vol. 16, no. 5, pp. 5582-5597, 2024/02/07 2024, doi: 10.1021/acsami.3c16544.
[47] Zhao Q., Ni Y., Wei H., Duan Y., Chen J., Xiao Q. et al., "Ion incorporation into bone grafting materials," Periodontology 2000, vol. 94, no. 1, pp. 213-230, Feb 2024, doi: 10.1111/prd.12533.
[48] Jahnen-Dechent Wilhelm and Ketteler Markus, "Magnesium basics," Clinical Kidney Journal, vol. 5, no. Suppl_1, pp. i3-i14, 2012, doi: 10.1093/ndtplus/sfr163.
[49] Kuang Xiaoqing, Chiou Jiachi, Lo Kenneth, and Wen Chunyi, "Magnesium in joint health and osteoarthritis," Nutrition Research, vol. 90, pp. 24-35, 2021/06/01/ 2021, doi: 10.1016/j.nutres.2021.03.002.
[50] Martinez Sanchez Adela H., Feyerabend Frank, Laipple Daniel, Willumeit-Römer Regine, Weinberg Annelie, and Luthringer Bérengère J. C., "Chondrogenic differentiation of ATDC5-cells under the influence of Mg and Mg alloy degradation," Materials Science and Engineering: C, vol. 72, pp. 378-388, 2017/03/01/ 2017, doi: 10.1016/j.msec.2016.11.062.
[51] Park Kwang-Sook, Kim Byoung-Ju, Lih Eugene, Park Wooram, Lee Soo-Hong, Joung Yoon Ki et al., "Versatile effects of magnesium hydroxide nanoparticles in PLGA scaffold–mediated chondrogenesis," Acta Biomaterialia, vol. 73, pp. 204-216, 2018/06/01/ 2018, doi: 10.1016/j.actbio.2018.04.022.
[52] Yue J. J., Jin S. Z., Gu S. Z., Sun R., and Lian Q. W., "High concentration magnesium inhibits extracellular matrix calcification and protects articular cartilage via Erk/autophagy pathway," Journal of Cellular Physiology, vol. 234, no. 12, pp. 23190-23201, Dec 2019, doi: 10.1002/jcp.28885.
[53] Shimaya M., Muneta T., Ichinose S., Tsuji K., and Sekiya I., "Magnesium enhances adherence and cartilage formation of synovial mesenchymal stem cells through integrins," Osteoarthritis and Cartilage, vol. 18, no. 10, pp. 1300-1309, 2010/10/01/ 2010, doi: 10.1016/j.joca.2010.06.005.
[54] Stefanidou M., Maravelias C., Dona A., and Spiliopoulou C., "Zinc: a multipurpose trace element," Archives of Toxicology, vol. 80, no. 1, pp. 1-9, 2006/01/01 2006, doi: 10.1007/s00204-005-0009-5.
[55] Olechnowicz J., Tinkov A., Skalny A., and Suliburska Joanna, "Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism," The Journal of Physiological Sciences, vol. 68, no. 1, pp. 19-31, 2018/01/01 2018, doi: 10.1007/s12576-017-0571-7.
[56] Ciaffaglione V. and Rizzarelli E., "Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection," International Journal of Molecular Sciences, vol. 24, no. 22, Nov 11 2023, doi: 10.3390/ijms242216209.
[57] Maleki-Ghaleh H., Siadati M. H., Fallah A., Koc B., Kavanlouei M., Khademi-Azandehi P. et al., "Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering," International Journal of Molecular Sciences, vol. 22, no. 17, p. 9564, 2021, doi: 10.3390%2Fijms22179564.
[58] Wang Xibin, Leach Roland M., Fosmire Gary J., and Gay Carol V., "Short-Term Zinc Deficiency Inhibits Chondrocyte Proliferation and Induces Cell Apoptosis in the Epiphyseal Growth Plate of Young Chickens," The Journal of Nutrition, vol. 132, no. 4, pp. 665-673, 2002/04/01/ 2002, doi: 10.1093/jn/132.4.665.
[59] Rodriguez J. P. and Rosselot G., "Effects of zinc on cell proliferation and proteoglycan characteristics of epiphyseal chondrocytes," Journal of Cellular Biochemistry, vol. 82, no. 3, pp. 501-11, 2001, doi: 10.1002/jcb.1178.
[60] Frangos Theoharris and Maret Wolfgang, "Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis," Nutrients, vol. 13, no. 1, p. 53, 2021, doi: 10.3390/nu13010053.
[61] Ruminski Peter G., Massa Mark, Strohbach Joseph, Hanau Cathleen E., Schmidt Michelle, Scholten Jeffrey A. et al., "Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis," Journal of Medicinal Chemistry, vol. 59, no. 1, pp. 313-327, 2016/01/14 2016, doi: 10.1021/acs.jmedchem.5b01434.
[62] Zhang Kunyu, Lin Sien, Feng Qian, Dong Chaoqun, Yang Yanhua, Li Gang et al., "Nanocomposite hydrogels stabilized by self-assembled multivalent bisphosphonate-magnesium nanoparticles mediate sustained release of magnesium ion and promote in-situ bone regeneration," Acta Biomaterialia, vol. 64, pp. 389-400, 2017/12/01/ 2017, doi: 10.1016/j.actbio.2017.09.039.
[63] Plum Laura M., Rink Lothar, and Haase Hajo, "The Essential Toxin: Impact of Zinc on Human Health," International Journal of Environmental Research and Public Health, vol. 7, no. 4, pp. 1342-1365, 2010, doi: 10.3390/ijerph7041342.
[64] Feyerabend Frank, Witte Frank, Kammal Michael, and Willumeit Regine, "Unphysiologically High Magnesium Concentrations Support Chondrocyte Proliferation and Redifferentiation," Tissue Engineering, vol. 12, no. 12, pp. 3545-3556, 2006/12/01 2006, doi: 10.1089/ten.2006.12.3545.
[65] Li Xuefei, Qin Hongling, Zhang Xiaolong, and Guo Zhiguang, "Triple-network hydrogels with high strength, low friction and self-healing by chemical-physical crosslinking," Journal of Colloid and Interface Science, vol. 556, pp. 549-556, 2019/11/15/ 2019, doi: 10.1016/j.jcis.2019.08.100.
[66] Balakrishnan Biji and Banerjee R., "Biopolymer-Based Hydrogels for Cartilage Tissue Engineering," Chemical Reviews, vol. 111, no. 8, pp. 4453-4474, 2011/08/10 2011, doi: 10.1021/cr100123h.
[67] Griffon Dominique J., Sedighi M. Reza, Schaeffer David V., Eurell Jo Ann, and Johnson Ann L., "Chitosan scaffolds: Interconnective pore size and cartilage engineering," Acta Biomaterialia, vol. 2, no. 3, pp. 313-320, 2006, doi: 10.1016/j.actbio.2005.12.007.
[68] Ma Yuan, Wang Xinhui, Su Ting, Lu Feng, Chang Qiang, and Gao Jianhua, "Recent Advances in Macroporous Hydrogels for Cell Behavior and Tissue Engineering," Gels, vol. 8, no. 10, p. 606, 2022, doi: 10.3390/gels8100606.
[69] Li Zhi, Chen Li, Xu Mengting, Ma Yan, Chen Lei, and Dai Fangyin, "Double crosslinking hydrogel with tunable properties for potential biomedical application," Journal of Polymer Research, vol. 27, no. 9, p. 262, 2020/08/11 2020, doi: 10.1007/s10965-020-02242-x.
[70] Chamkouri Hossein, "A Review of Hydrogels, Their Properties and Applications in Medicine," American Journal of Biomedical Science & Research, vol. 11, no. 6, pp. 485-493, 2021, doi: 10.34297/ajbsr.2021.11.001682.
[71] Daza Agudelo Jorge I., Ramirez María R., Henquin Eduardo R., and Rintoul Ignacio, "Modelling of swelling of PVA hydrogels considering non-ideal mixing behaviour of PVA and water," Journal of Materials Chemistry B, vol. 7, no. 25, pp. 4049-4054, 2019, doi: 10.1039/C9TB00243J.
[72] Greenwal.Ra, A. Tsang, H. S. Diamond, and Josephso.As, "Human Cartilage Lysozyme," J Clin Invest, vol. 51, no. 9, pp. 2264-+, 1972, doi: 10.1172/Jci107035.
[73] Smirnow J. and Wislowska M., "Lysozyme and its biological value in rheumatoid arthritis (RA)," Arthritis Research & Therapy, vol. 3, no. 2, p. P014, 2001/01/26 2001, doi: 10.1186/ar183.
[74] Kopacz-Bednarska A., Król T., Trybus E., Trybus W., Zaporowska H., Kolaczek K. et al., "In Vitro and In Vivo Effects of Magnesium on the Lysosomal System," Folia Biologica (Kraków), vol. 66, no. 4, pp. 179-191, 2018, doi: 10.3409/fb_66-4.19.
[75] Lončarević Andrea, Malbaša Zoran, Kovačić Marin, Ostojić Karla, Angaïts Ange, Skoko Željko et al., "Copper–zinc/chitosan complex hydrogels: Rheological, degradation and biological properties," International Journal of Biological Macromolecules, vol. 251, p. 126373, 2023/11/01/ 2023, doi: 10.1016/j.ijbiomac.2023.126373.
[76] Park C. H., Kimler B. F., and Smith T. K., "Comparison of the supravital DNA dyes Hoechst 33342 and DAPI for flow cytometry and clonogenicity studies of human leukemic marrow cells," Experimental Hematology, vol. 13, no. 10, pp. 1039-43, Nov 1985.
[77] Burgess D., Cottrell J., Iverson T., "Zinc chloride treatment in ATDC5 cells induces chondrocyte maturation," International Journal of Regenerative Medicine, 2018;1:1–11, doi: 10.31487/j.RGM.2018.02.008.
[78] Huang T.-C., Chang W.-T., Hu Y.-C., Hsieh B.-S., Cheng H.-L., Yen J.-H., Chiu P.-R., Chang K.-L., "Zinc Protects Articular Chondrocytes through Changes in Nrf2-Mediated Antioxidants, Cytokines and Matrix Metalloproteinases," Nutrients, 2018;10:471, doi: 10.3390/nu10040471.
[79] Day Timothy F., Guo Xizhi, Garrett-Beal Lisa, and Yang Yingzi, "Wnt/β-Catenin Signaling in Mesenchymal Progenitors Controls Osteoblast and Chondrocyte Differentiation during Vertebrate Skeletogenesis," Developmental Cell, vol. 8, no. 5, pp. 739-750, 2005/05/01/ 2005, doi: 10.1016/j.devcel.2005.03.016.
[80] St-Jacques B., Hammerschmidt M., and McMahon A. P., "Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation," Genes & Development, vol. 13, no. 16, pp. 2072-86, Aug 15 1999, doi: 10.1101/gad.13.16.2072.