Development And Formulation Of Drug-Loaded Hydrogel For Cartilage Regenerative Potential
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Abstract
Cartilage damage and degeneration pose significant challenges in orthopedic medicine, innovative approaches for regenerative therapies. The hydrogel is designed to provide a supportive matrix for cell growth and differentiation while delivering therapeutic agents to promote tissue repair. Drug-loaded hydrogels have been extensively studied for cartilage regenerative medicine, offering promising results for tissue engineering and drug delivery applications. These hydrogels, composed of homopolymers and copolymers, can absorb water and create an appropriate microenvironment similar to the extracellular matrix (ECM). Various polymers and crosslinking methods are explored to optimize the hydrogel's mechanical properties, biocompatibility, and drug release kinetics. Additionally, the study investigates the efficacy of different drugs, growth factors, and bioactive molecules for enhancing chondrogenesis and cartilage regeneration within the hydrogel scaffold. The developed drug-loaded hydrogel holds great promise for addressing the unmet clinical need for effective cartilage regenerative therapies, offering potential advancements in orthopedic medicine.
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References
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Moreira-Teixeira LS, Georgi N, Leijten J, Wu L, Karperien M. Cartilage tissue engineering. Endocr Dev. 2011;21:102-115. Doi: 10.1159/000328140. Epub 2011 Aug 22. PMID: 21865759.
Ming-Yeah Hu., Syam Nukauarpu., Scaffolds for Cartilage Tissue Engineering. 2019, Pages 211-244 Https://Doi.Org/10.1016/B978-0-08-102563-5.00011-3.
Wasyłeczko M, Sikorska W, Chwojnowski A. Review of Synthetic and Hybrid Scaffolds in Cartilage Tissue Engineering. Membranes (Basel). 2020 Nov 17;10(11):348. Doi: 10.3390/membranes10110348. PMID: 33212901; PMCID: PMC7698415.
Shailesh Kumar Singh, Archana Dhyani. Divya Juyal., Hydrogel: Preparation, Characterization and Applications., 2017; 6(6): 25-32.
Nahideh Asadi, Effat Alizadeh, Roya Salehi, Bahar Khalandi, Soodabeh Davaran & Abolfazl Akbarzadeh (2018) Nanocomposite hydrogels for cartilage tissue engineering: a review, Artificial Cells, Nanomedicine, and Biotechnology, 46:3, 465-471, DOI: 10.1080/21691401.2017.1345924
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Kitamura N, Yokota M, Kurokawa T, Gong JP, Yasuda K. In vivo cartilage regeneration induced by a double-network hydrogel: Evaluation of a novel therapeutic strategy for femoral articular cartilage defects in a sheep model. J Biomed Mater Res A. 2016 Sep;104(9):2159-65. Doi: 10.1002/jbm.a.35745. Epub 2016 May 3. PMID: 27087198.
Ogawa M, Kitamura N, Kurokawa T, Arakaki K, Tanaka Y, Gong JP, Yasuda K. Poly(2-acrylamido-2-methylpropanesulfonic acid) gel induces articular cartilage regeneration in vivo: comparisons of the induction ability between single- and double-network gels. J Biomed Mater Res A. 2012 Sep;100(9):2244-51. Doi: 10.1002/jbm.a.34165. Epub 2012 Apr 10. PMID: 22492713.
Imabuchi R, Ohmiya Y, Kwon HJ, Onodera S, Kitamura N, Kurokawa T, Gong JP, Yasuda K. Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: comparisons with the normal articular cartilage. BMC Musculoskelet Disord. 2011 Sep 29;12:213. Doi: 10.1186/1471-2474-12-213. PMID: 21955995; PMCID: PMC3192715.
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Reddi AH, Becerra J, Andrades JA. Nanomaterials and hydrogel scaffolds for articular cartilage regeneration. Tissue Eng Part B Rev. 2011 Oct;17(5):301-5. Doi: 10.1089/ten.TEB.2011.0141. Epub 2011 Aug 29. PMID: 21595612.
Gobbi A, Kon E, Berruto M, Francisco R, Filardo G, Marcacci M. Patellofemoral full-thickness chondral defects treated with Hyalograft-C: a clinical, arthroscopic, and histologic review. Am J Sports Med. 2006 Nov;34(11):1763-73. Doi: 10.1177/0363546506288853. Epub 2006 Jul 10. PMID: 16832129.
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Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008 Jan;58(1):26-35. Doi: 10.1002/art.23176. PMID: 18163497; PMCID: PMC3266664.
Ateshian GA. Artificial cartilage: weaving in three dimensions. Nat Mater. 2007 Feb;6(2):89-90. Doi: 10.1038/nmat1830. PMID: 17268489.
Moreira-Teixeira LS, Georgi N, Leijten J, Wu L, Karperien M. Cartilage tissue engineering. Endocr Dev. 2011;21:102-115. Doi: 10.1159/000328140. Epub 2011 Aug 22. PMID: 21865759.
Ming-Yeah Hu., Syam Nukauarpu., Scaffolds for Cartilage Tissue Engineering. 2019, Pages 211-244 Https://Doi.Org/10.1016/B978-0-08-102563-5.00011-3.
Wasyłeczko M, Sikorska W, Chwojnowski A. Review of Synthetic and Hybrid Scaffolds in Cartilage Tissue Engineering. Membranes (Basel). 2020 Nov 17;10(11):348. Doi: 10.3390/membranes10110348. PMID: 33212901; PMCID: PMC7698415.
Shailesh Kumar Singh, Archana Dhyani. Divya Juyal., Hydrogel: Preparation, Characterization and Applications., 2017; 6(6): 25-32.
Nahideh Asadi, Effat Alizadeh, Roya Salehi, Bahar Khalandi, Soodabeh Davaran & Abolfazl Akbarzadeh (2018) Nanocomposite hydrogels for cartilage tissue engineering: a review, Artificial Cells, Nanomedicine, and Biotechnology, 46:3, 465-471, DOI: 10.1080/21691401.2017.1345924
Bashir S, Hina M, Iqbal J, Rajpar AH, Mujtaba MA, Alghamdi NA, Wageh S, Ramesh K, Ramesh S. Fundamental Concepts of Hydrogels: Synthesis, Properties, and Their Applications. Polymers (Basel). 2020 Nov 16;12(11):2702. Doi: 10.3390/polym12112702. PMID: 33207715; PMCID: PMC7697203.
Vega SL, Kwon MY, Burdick JA. Recent advances in hydrogels for cartilage tissue engineering. Eur Cell Mater. 2017 Jan 30;33:59-75. Doi: 10.22203/eCM.v033a05. PMID: 28138955; PMCID: PMC5748291.
Ingavle GC, Frei AW, Gehrke SH, Detamore MS. Incorporation of aggrecan in interpenetrating network hydrogels to improve cellular performance for cartilage tissue engineering. Tissue Eng Part A. 2013 Jun;19(11-12):1349-59. Doi: 10.1089/ten.TEA.2012.0160. Epub 2013 Mar 26. PMID: 23379843; PMCID: PMC3638541.
Snyder TN, Madhavan K, Intrator M, Dregalla RC, Park D. A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and potential for articular cartilage repair. J Biol Eng. 2014 May 1;8:10. Doi: 10.1186/1754-1611-8-10. Erratum in: J Biol Eng. 2014;8:27. PMID: 25061479; PMCID: PMC4109069.
Dinescu S, Galateanu B, Radu E, Hermenean A, Lungu A, Stancu IC, Jianu D, Tumbar T, Costache M. A 3D Porous Gelatin-Alginate-Based-IPN Acts as an Efficient Promoter of Chondrogenesis from Human Adipose-Derived Stem Cells. Stem Cells Int. 2015;2015:252909. Doi: 10.1155/2015/252909. Epub 2015 May 27. PMID: 26106422; PMCID: PMC4461772.
Liao IC, Moutos FT, Estes BT, Zhao X, Guilak F. Composite three-dimensional woven scaffolds with interpenetrating network hydrogels to create functional synthetic articular cartilage. Adv Funct Mater. 2013 Dec 17;23(47):5833-5839. Doi: 10.1002/adfm.201300483. PMID: 24578679; PMCID: PMC3933181.
Guo Y, Yuan T, Xiao Z, Tang P, Xiao Y, Fan Y, Zhang X. Hydrogels of collagen/chondroitin sulfate/hyaluronan interpenetrating polymer network for cartilage tissue engineering. J Mater Sci Mater Med. 2012 Sep;23(9):2267-79. Doi: 10.1007/s10856-012-4684-5. Epub 2012 May 26. PMID: 22639153.
Park H, Choi B, Hu J, Lee M. Injectable chitosan hyaluronic acid hydrogels for cartilage tissue engineering. Acta Biomater. 2013 Jan;9(1):4779-86. Doi: 10.1016/j.actbio.2012.08.033. Epub 2012 Aug 27. PMID: 22935326.
Skaalure SC, Dimson SO, Pennington AM, Bryant SJ. Semi-interpenetrating networks of hyaluronic acid in degradable PEG hydrogels for cartilage tissue engineering. Acta Biomater. 2014 Aug;10(8):3409-20. Doi: 10.1016/j.actbio.2014.04.013. Epub 2014 Apr 24. PMID: 24769116.
Little CJ, Kulyk WM, Chen X. The Effect of Chondroitin Sulphate and Hyaluronic Acid on Chondrocytes Cultured within a Fibrin-Alginate Hydrogel. J Funct Biomater. 2014 Sep 18;5(3):197-210. Doi: 10.3390/jfb5030197. PMID: 25238548; PMCID: PMC4192613.
Arnold MP, Daniels AU, Ronken S, García HA, Friederich NF, Kurokawa T, Gong JP, Wirz D. Acrylamide Polymer Double-Network Hydrogels: Candidate Cartilage Repair Materials with Cartilage-Like Dynamic Stiffness and Attractive Surgery-Related Attachment Mechanics. Cartilage. 2011 Oct;2(4):374-83. Doi: 10.1177/1947603511402320. PMID: 26069595; PMCID: PMC4297135.
Yasuda K, Kitamura N, Gong JP, Arakaki K, Kwon HJ, Onodera S, Chen YM, Kurokawa T, Kanaya F, Ohmiya Y, Osada Y. A novel double-network hydrogel induces spontaneous articular cartilage regeneration in vivo in a large osteochondral defect. Macromol Biosci. 2009 Apr 8;9(4):307-16. Doi: 10.1002/mabi.200800223. PMID: 19031389.
Kitamura N, Yokota M, Kurokawa T, Gong JP, Yasuda K. In vivo cartilage regeneration induced by a double-network hydrogel: Evaluation of a novel therapeutic strategy for femoral articular cartilage defects in a sheep model. J Biomed Mater Res A. 2016 Sep;104(9):2159-65. Doi: 10.1002/jbm.a.35745. Epub 2016 May 3. PMID: 27087198.
Ogawa M, Kitamura N, Kurokawa T, Arakaki K, Tanaka Y, Gong JP, Yasuda K. Poly(2-acrylamido-2-methylpropanesulfonic acid) gel induces articular cartilage regeneration in vivo: comparisons of the induction ability between single- and double-network gels. J Biomed Mater Res A. 2012 Sep;100(9):2244-51. Doi: 10.1002/jbm.a.34165. Epub 2012 Apr 10. PMID: 22492713.
Imabuchi R, Ohmiya Y, Kwon HJ, Onodera S, Kitamura N, Kurokawa T, Gong JP, Yasuda K. Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: comparisons with the normal articular cartilage. BMC Musculoskelet Disord. 2011 Sep 29;12:213. Doi: 10.1186/1471-2474-12-213. PMID: 21955995; PMCID: PMC3192715.
Fukui T, Kitamura N, Kurokawa T, Yokota M, Kondo E, Gong JP, Yasuda K. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel. J Mater Sci Mater Med. 2014 Apr;25(4):1173-82. Doi: 10.1007/s10856-013-5139-3. Epub 2014 Jan 7. PMID: 24394983.
Levett PA, Hutmacher DW, Malda J, Klein TJ. Hyaluronic acid enhances the mechanical properties of tissue-engineered cartilage constructs. PLoS One. 2014 Dec 1;9(12):e113216. Doi: 10.1371/journal.pone.0113216. PMID: 25438040; PMCID: PMC4249877.
Rodell CB, Dusaj NN, Highley CB, Burdick JA. Injectable and Cytocompatible Tough Double-Network Hydrogels through Tandem Supramolecular and Covalent Crosslinking. Adv Mater. 2016 Oct;28(38):8419-8424. Doi: 10.1002/adma.201602268. Epub 2016 Aug 1. PMID: 27479881; PMCID: PMC7437955.
Moreira Teixeira LS, Bijl S, Pully VV, Otto C, Jin R, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M. Self-attaching and cell-attracting in-situ forming dextran-tyramine conjugates hydrogels for arthroscopic cartilage repair. Biomaterials. 2012 Apr;33(11):3164-74. Doi: 10.1016/j.biomaterials.2012.01.001. Epub 2012 Jan 20. PMID: 22265787.
Jin R, Moreira Teixeira LS, Dijkstra PJ, van Blitterswijk CA, Karperien M, Feijen J. Chondrogenesis in injectable enzymatically crosslinked heparin/dextran hydrogels. J Control Release. 2011 May 30;152(1):186-95. Doi: 10.1016/j.jconrel.2011.01.031. Epub 2011 Feb 1. PMID: 21291927.
Palumbo FS, Fiorica C, Di Stefano M, Pitarresi G, Gulino A, Agnello S, Giammona G. In situ forming hydrogels of hyaluronic acid and inulin derivatives for cartilage regeneration. Carbohydr Polym. 2015 May 20;122:408-16. Doi: 10.1016/j.carbpol.2014.11.002. Epub 2014 Nov 8. PMID: 25817685.
Tuan RS, Chen AF, Klatt BA. Cartilage regeneration. J Am Acad Orthop Surg. 2013 May;21(5):303-11. Doi: 10.5435/JAAOS-21-05-303. PMID: 23637149; PMCID: PMC4886741.
Ruoslahti E. RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol. 1996;12:697-715. Doi: 10.1146/annurev.cellbio.12.1.697. PMID: 8970741.
Crawford DC, DeBerardino TM, Williams RJ 3rd. NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years. J Bone Joint Surg Am. 2012 Jun 6;94(11):979-89. Doi: 10.2106/JBJS.K.00533. PMID: 22637204.
Reddi AH, Becerra J, Andrades JA. Nanomaterials and hydrogel scaffolds for articular cartilage regeneration. Tissue Eng Part B Rev. 2011 Oct;17(5):301-5. Doi: 10.1089/ten.TEB.2011.0141. Epub 2011 Aug 29. PMID: 21595612.
Gobbi A, Kon E, Berruto M, Francisco R, Filardo G, Marcacci M. Patellofemoral full-thickness chondral defects treated with Hyalograft-C: a clinical, arthroscopic, and histologic review. Am J Sports Med. 2006 Nov;34(11):1763-73. Doi: 10.1177/0363546506288853. Epub 2006 Jul 10. PMID: 16832129.
Filardo G, Kon E, Di Martino A, Iacono F, Marcacci M. Arthroscopic second-generation autologous chondrocyte implantation: a prospective 7-year follow-up study. Am J Sports Med. 2011 Oct;39(10):2153-60. Doi: 10.1177/0363546511415658. Epub 2011 Jul 29. PMID: 21803978.
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