Hydrogels Platforms Addressing the Multiple Applications in Medicinal and Drug Delivery: A Critical Review
Abstract
Hydrogels are three-dimensional polymeric networks renowned for their remarkable water-absorbing capacity, tunable physicochemical properties, and high biocompatibility. This review comprehensively explores the synthesis, classification, and physicochemical and biological characteristics of both natural and synthetic hydrogels. Advances in crosslinking mechanisms, including ionic, chemical, and physical methods, are critically analyzed alongside their functional properties such as pH-, temperature-, and photo-responsiveness. Special emphasis is given to the role of hydrogels in drug delivery systems, including buccal, oral, vaginal, transdermal, ocular, and injectable formulations. Additionally, their applications in wound healing, tissue engineering, biosensing, and 3D cell cultures are examined. Limitations and challenges in clinical translation, regulatory concerns, scale-up processes, and strategies to enhance drug loading and controlled release are discussed. The review underscores the transformative potential of hydrogels in personalized and regenerative medicine and calls for further translational research to address current constraints and expand clinical applicability.
Keywords: Hydrogel, crosslinked hydrogel, drug delivery, polymerization
Keywords:
Hydrogels, Crosslinked hydrogel, Drug delivery, PolymerizationDOI
https://doi.org/10.22270/jddt.v15i7.7236References
1. Ahsan A, Tian WX, Farooq MA, Khan DH. An overview of hydrogels and their role in transdermal drug delivery. International Journal of Polymeric Materials and Polymeric Biomaterials. 2021 May 25;70(8):574-84. https://doi.org/10.1080/00914037.2020.1740989
2. Han Z, Wang P, Mao G, Yin T, Zhong D, Yiming B, Hu X, Jia Z, Nian G, Qu S, Yang W. Dual pH-responsive hydrogel actuator for lipophilic drug delivery. ACS applied materials & interfaces. 2020 Feb 13;12(10):12010-7. https://doi.org/10.1021/acsami.9b21713 PMid:32053341
3. Suflet DM, Popescu I, Pelin IM, Ichim DL, Daraba OM, Constantin M, Fundueanu G. Dual cross-linked chitosan/PVA hydrogels containing silver nanoparticles with antimicrobial properties. Pharmaceutics. 2021 Sep 13;13(9):1461. https://doi.org/10.3390/pharmaceutics13091461 PMid:34575536 PMCid:PMC8465188
4. Madihally SV, Matthew HW. Porous chitosan scaffolds for tissue engineering. Biomaterials. 1999 Jun 1;20(12):1133-42. https://doi.org/10.1016/S0142-9612(99)00011-3 PMid:10382829
5. Pelin IM, Suflet DM. Mucoadhesive buccal drug delivery systems containing polysaccharides. Cellul. Chem. Technol. 2020 Sep 1;54:889-902. https://doi.org/10.35812/CelluloseChemTechnol.2020.54.86
6. Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. European journal of pharmaceutics and biopharmaceutics. 2012 Aug 1;81(3):463-9. https://doi.org/10.1016/j.ejpb.2012.04.007 PMid:22561955
7. Panjapheree K, Kamonmattayakul S, Meesane J. Biphasic scaffolds of silk fibroin film affixed to silk fibroin/chitosan sponge based on surgical design for cartilage defect in osteoarthritis. Materials & Design. 2018 Mar 5;141:323-32. https://doi.org/10.1016/j.matdes.2018.01.006
8. Coviello T, Matricardi P, Marianecci C, Alhaique F. Polysaccharide hydrogels for modified release formulations. Journal of controlled release. 2007 May 14;119(1):5-24. https://doi.org/10.1016/j.jconrel.2007.01.004 PMid:17382422
9. Burkert S, Schmidt T, Gohs U, Dorschner H, Arndt KF. Cross-linking of poly (N-vinyl pyrrolidone) films by electron beam irradiation. Radiation Physics and Chemistry. 2007 Aug 1;76(8-9):1324-8. https://doi.org/10.1016/j.radphyschem.2007.02.024
10. Jose J, Athira VP, Michel H, Hafeela AR, Bhat SG, Thomas S, Maria LP. Hydrogels: An overview of the history, classification, principles, applications, and kinetics. Sustainable Hydrogels. 2023 Jan 1:1-22. https://doi.org/10.1016/B978-0-323-91753-7.00005-3
11. Van Bemmelen JM. Das hydrogel und das krystallinische hydrat des kupferoxyds. Zeitschrift für anorganische Chemie. 1894;5(1):466-83. https://doi.org/10.1002/zaac.18940050156
12. Wichterle O, Lim D. Hydrophilic gels for biological use. Nature. 1960 Jan 9;185(4706):117-8. https://doi.org/10.1038/185117a0
13. Jokl J, Kopeček J, Lim D. Mechanism of three‐dimensional polymerization of the system methyl methacrylate-glycol dimethacrylate. I. Determination of the structure of the three‐dimensional product. Journal of Polymer Science Part A‐1: Polymer Chemistry. 1968 Nov;6(11):3041-8. https://doi.org/10.1002/pol.1968.150061108
14. Macret M, Hild G. Hydroxyalkyl methacrylates: hydrogel formation based on the radical copolymerization of 2-hydroxyethylmethacrylate and 2, 3-dihydroxypropylmethacrylate. Polymer. 1982 May 1;23(5):748-53. https://doi.org/10.1016/0032-3861(82)90063-5
15. Ikada Y, Mita T, Horii F, Sakurada I, Hatada M. Preparation of hydrogels by radiation technique. Radiation Physics and Chemistry (1977). 1977 Jan 1;9(4-6):633-45. https://doi.org/10.1016/0146-5724(77)90177-7
16. Zhu J. Bioactive modification of poly (ethylene glycol) hydrogels for tissue engineering. Biomaterials. 2010 Jun 1;31(17):4639-56. https://doi.org/10.1016/j.biomaterials.2010.02.044 PMid:20303169 PMCid:PMC2907908
17. Kopecek J. Hydrogels: From soft contact lenses and implants to self‐assembled nanomaterials. Journal of Polymer Science Part A: Polymer Chemistry. 2009 Nov 15;47(22):5929-46. https://doi.org/10.1002/pola.23607 PMid:19918374 PMCid:PMC2776732
18. Chen-Chow PC, Frank SG. In vitro release of lidocaine from Pluronic F-127 gels. International journal of pharmaceutics. 1981 Apr 1;8(2):89-99. https://doi.org/10.1016/0378-5173(81)90013-2
19. Wu XS, Hoffman AS, Yager P. Synthesis and characterization of thermally reversible macroporous poly (N‐isopropylacrylamide) hydrogels. Journal of Polymer Science Part A: Polymer Chemistry. 1992 Sep;30(10):2121-9. https://doi.org/10.1002/pola.1992.080301005
20. Vermonden T, Besseling NA, van Steenbergen MJ, Hennink WE. Rheological studies of thermosensitive triblock copolymer hydrogels. Langmuir. 2006 Nov 21;22(24):10180-4. https://doi.org/10.1021/la062224m PMid:17107019
21. Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug discovery today. 2002 May 15;7(10):569-79. https://doi.org/10.1016/S1359-6446(02)02255-9 PMid:12047857
22. Hassan CM, Doyle FJ, Peppas NA. Dynamic behavior of glucose-responsive poly (methacrylic acid-g-ethylene glycol) hydrogels. Macromolecules. 1997 Oct 6;30(20):6166-73. https://doi.org/10.1021/ma970117g
23. Ikada Y, Jamshidi K, Tsuji H, Hyon SH. Stereocomplex formation between enantiomeric poly (lactides). Macromolecules. 1987 Jul;20(4):904-6. https://doi.org/10.1021/ma00170a034
24. Buwalda SJ, Boere KW, Dijkstra PJ, Feijen J, Vermonden T, Hennink WE. Hydrogels in a historical perspective: From simple networks to smart materials. Journal of controlled release. 2014 Sep 28;190:254-73. https://doi.org/10.1016/j.jconrel.2014.03.052 PMid:24746623
25. Buwalda SJ, Boere KW, Dijkstra PJ, Feijen J, Vermonden T, Hennink WE. Hydrogels in a historical perspective: From simple networks to smart materials. Journal of controlled release. 2014 Sep 28;190:254-73. https://doi.org/10.1016/j.jconrel.2014.03.052 PMid:24746623
26. 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. 2020 Nov 16;12(11):2702. https://doi.org/10.3390/polym12112702 PMid:33207715 PMCid:PMC7697203
27. Kaczmarek B, Nadolna K, Owczarek A. The physical and chemical properties of hydrogels based on natural polymers. Hydrogels based on natural polymers. 2020 Jan 1:151-72. https://doi.org/10.1016/B978-0-12-816421-1.00006-9
28. Savić Gajić IM, Savić IM, Svirčev Z. Preparation and characterization of alginate hydrogels with high water-retaining capacity. Polymers. 2023 Jun 7;15(12):2592. https://doi.org/10.3390/polym15122592 PMid:37376238 PMCid:PMC10303585
29. Matsumoto K, Sakikawa N, Miyata T. Thermo-responsive gels that absorb moisture and ooze water. Nature communications. 2018 Jun 13;9(1):2315. https://doi.org/10.1038/s41467-018-04810-8 PMid:29899417 PMCid:PMC5998054
30. Ali S, Ranjha NM, Ahmad B, Khan AA, Hassan FU, Aziz T, Alharb M, Alshammari A, Alasmari AF, Alharbi ME. Sustained release of drug facilitated through chemically crosslinked polyvinyl alcohol-gelatin (PVA-GE) hydrogels. A sustainable biomedical approach. Polish Journal of Chemical Technology. 2023;25(2). https://doi.org/10.2478/pjct-2023-0017
31. Ding L, Song S, Chen L, Shi J, Zhao B, Teng G, Zhang J. A freeze-thawing method applied to the fabrication of 3-d curdlan/polyvinyl alcohol hydrogels as scaffolds for cell culture. International Journal of Biological Macromolecules. 2021 Mar 31;174:101-9. https://doi.org/10.1016/j.ijbiomac.2021.01.160 PMid:33513424
32. Ghobashy MM, Elbarbary AM, Hegazy DE. Gamma radiation synthesis of a novel amphiphilic terpolymer hydrogel pH-responsive based chitosan for colon cancer drug delivery. Carbohydrate Polymers. 2021 Jul 1;263:117975. https://doi.org/10.1016/j.carbpol.2021.117975 PMid:33858572
33. Chung TW, Tyan YC, Lin SW, Yang MH, Liu YH, Wang RP. Developing photothermal-responsive and anti-oxidative silk/dopamine nanoparticles decorated with drugs which were incorporated into silk films as a depot-based drug delivery. International Journal of Biological Macromolecules. 2021 Aug 31;185:122-33. https://doi.org/10.1016/j.ijbiomac.2021.06.084 PMid:34147523
34. Sgambato A, Cipolla L, Russo L. Bioresponsive hydrogels: Chemical strategies and perspectives in tissue engineering. Gels. 2016 Oct 14;2(4):28. https://doi.org/10.3390/gels2040028 PMid:30674158 PMCid:PMC6318637
35. Xing R, Mustapha O, Ali T, Rehman M, Zaidi SS, Baseer A, Batool S, Mukhtiar M, Shafique S, Malik M, Sohail S. Development, Characterization, and Evaluation of SLN‐Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery. BioMed Research International. 2021;2021(1):9968602. https://doi.org/10.1155/2021/9968602 PMid:34285920 PMCid:PMC8275402
36. Witika BA, Stander JC, Smith VJ, Walker RB. Nano co-crystal embedded stimuli-responsive hydrogels: A potential approach to treat HIV/AIDS. Pharmaceutics. 2021 Jan 20;13(2):127. https://doi.org/10.3390/pharmaceutics13020127 PMid:33498151 PMCid:PMC7908984
37. Huynh V, Ifraimov N, Wylie RG. Modulating the thermoresponse of polymer-protein conjugates with hydrogels for controlled release. Polymers. 2021 Aug 18;13(16):2772. https://doi.org/10.3390/polym13162772 PMid:34451311 PMCid:PMC8399950
38. Wei X, Gong C, Gou M, Fu S, Guo Q, Shi S, Luo F, Guo G, Qiu L, Qian Z. Biodegradable poly (ɛ-caprolactone)-poly (ethylene glycol) copolymers as drug delivery system. International journal of pharmaceutics. 2009 Oct 20;381(1):1-8. https://doi.org/10.1016/j.ijpharm.2009.07.033 PMid:19664700
39. Li X, Yu L, Zhang C, Niu X, Sun M, Yan Z, Wang W, Yuan Z. Tumor acid microenvironment-activated self-targeting & splitting gold nanoassembly for tumor chemo-radiotherapy. Bioactive Materials. 2022 Jan 1;7:377-88. https://doi.org/10.1016/j.bioactmat.2021.05.050 PMid:34466739 PMCid:PMC8379383
40. Qing W, Xing X, Feng D, Chen R, Liu Z. Indocyanine green loaded pH-responsive bortezomib supramolecular hydrogel for synergistic chemo-photothermal/photodynamic colorectal cancer therapy. Photodiagnosis and photodynamic therapy. 2021 Dec 1;36:102521. https://doi.org/10.1016/j.pdpdt.2021.102521 PMid:34481977
41. Lin X, Miao L, Wang X, Tian H. Design and evaluation of pH-responsive hydrogel for oral delivery of amifostine and study on its radioprotective effects. Colloids and Surfaces B: Biointerfaces. 2020 Nov 1;195:111200. https://doi.org/10.1016/j.colsurfb.2020.111200 PMid:32623053
42. Wang R, Yang Z, Luo J, Hsing IM, Sun F. B12-dependent photoresponsive protein hydrogels for controlled stem cell/protein release. Proceedings of the National Academy of Sciences. 2017 Jun 6;114(23):5912-7. https://doi.org/10.1073/pnas.1621350114 PMid:28533376 PMCid:PMC5468657
43. Ghani M, Heiskanen A, Thomsen P, Alm M, Emnéus J. Molecular-gated drug delivery systems using light-triggered hydrophobic-to-hydrophilic switches. ACS Applied Bio Materials. 2021 Jan 13;4(2):1624-31. https://doi.org/10.1021/acsabm.0c01458 PMid:35014511
44. Fan L, Zhang X, Liu X, Sun B, Li L, Zhao Y. Responsive Hydrogel Microcarrier‐Integrated Microneedles for Versatile and Controllable Drug Delivery. Advanced Healthcare Materials. 2021 May;10(9):2002249. https://doi.org/10.1002/adhm.202002249 PMid:33690992
45. Najafipour A, Gharieh A, Fassihi A, Sadeghi-Aliabadi H, Mahdavian AR. MTX-loaded dual thermoresponsive and pH-responsive magnetic hydrogel nanocomposite particles for combined controlled drug delivery and hyperthermia therapy of cancer. Molecular Pharmaceutics. 2020 Dec 10;18(1):275-84. https://doi.org/10.1021/acs.molpharmaceut.0c00910 PMid:33300343
46. Huang Y, Wang Z, Zhang G, Ren J, Yu L, Liu X, Yang Y, Ravindran A, Wong C, Chen R. A pH/redox-dual responsive, nanoemulsion-embedded hydrogel for efficient oral delivery and controlled intestinal release of magnesium ions. Journal of Materials Chemistry B. 2021;9(7):1888-95. https://doi.org/10.1039/D0TB02442B PMid:33533362
47. Pan Z, Ye H, Wu D. Recent advances on polymeric hydrogels as wound dressings. APL bioengineering. 2021 Mar 1;5(1). https://doi.org/10.1063/5.0038364 PMid:33644627 PMCid:PMC7889296
48. Liang Y, He J, Guo B. Functional hydrogels as wound dressing to enhance wound healing. ACS nano. 2021 Aug 10;15(8):12687-722. https://doi.org/10.1021/acsnano.1c04206 PMid:34374515
49. Zhu L, Chen L. Facile design and development of nano-clustery graphene-based macromolecular protein hydrogel loaded with ciprofloxacin to antibacterial improvement for the treatment of burn wound injury. Polymer Bulletin. 2022 Sep 1:1-6.
50. Khaliq T, Sohail M, Minhas MU, Shah SA, Jabeen N, Khan S, Hussain Z, Mahmood A, Kousar M, Rashid H. Self-crosslinked chitosan/κ-carrageenan-based biomimetic membranes to combat diabetic burn wound infections. International Journal of Biological Macromolecules. 2022 Feb 1;197:157-68. https://doi.org/10.1016/j.ijbiomac.2021.12.100 PMid:34968540
51. Haidari H, Kopecki Z, Sutton AT, Garg S, Cowin AJ, Vasilev K. pH-responsive "smart" hydrogel for controlled delivery of silver nanoparticles to infected wounds. Antibiotics. 2021 Jan 5;10(1):49. https://doi.org/10.3390/antibiotics10010049 PMid:33466534 PMCid:PMC7824857
52. Zhang L, Zhou Y, Su D, Wu S, Zhou J, Chen J. Injectable, self-healing and pH responsive stem cell factor loaded collagen hydrogel as a dynamic bioadhesive dressing for diabetic wound repair. Journal of Materials Chemistry B. 2021;9(29):5887-97. https://doi.org/10.1039/D1TB01163D PMid:34259303
53. Wang Y, Wu Y, Long L, Yang L, Fu D, Hu C, Kong Q, Wang Y. Inflammation-responsive drug-loaded hydrogels with sequential hemostasis, antibacterial, and anti-inflammatory behavior for chronically infected diabetic wound treatment. ACS applied materials & interfaces. 2021 Jul 9;13(28):33584-99. https://doi.org/10.1021/acsami.1c09889 PMid:34240605
54. Huang L, Shi Y, Li M, Wang T, Zhao L. Plasma exosomes loaded pH-responsive carboxymethylcellulose hydrogel promotes wound repair by activating the vascular endothelial growth factor signaling pathway in type 1 diabetic mice. Journal of biomedical nanotechnology. 2021 Oct 1;17(10). https://doi.org/10.1166/jbn.2021.3165 PMid:34706802
55. Yang J, Chen Z, Pan D, Li H, Shen J. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. International journal of nanomedicine. 2020 Aug 11:5911-26. https://doi.org/10.2147/IJN.S249129 PMid:32848396 PMCid:PMC7429232
56. Xu J, Xu JJ, Lin Q, Jiang L, Zhang D, Li Z, Ma B, Zhang C, Li L, Kai D, Yu HD. Lignin-incorporated nanogel serving as an antioxidant biomaterial for wound healing. ACS Applied Bio Materials. 2020 Oct 1;4(1):3-13. https://doi.org/10.1021/acsabm.0c00858 PMid:35014273
57. Zhang J, Zhu Y, Zhang Y, Lin W, Ke J, Liu J, Zhang L, Liu J. A balanced charged hydrogel with anti-biofouling and antioxidant properties for treatment of irradiation-induced skin injury. Materials Science and Engineering: C. 2021 Dec 1;131:112538. https://doi.org/10.1016/j.msec.2021.112538 PMid:34857314
58. Wang S, Yuan L, Xu Z, Lin X, Ge L, Li D, Mu C. Functionalization of an electroactive self-healing polypyrrole-grafted gelatin-based hydrogel by incorporating a polydopamine@ AgNP nanocomposite. ACS Applied Bio Materials. 2021 Jul 7;4(7):5797-808. https://doi.org/10.1021/acsabm.1c00548 PMid:35006754
59. Zhao Y, Song S, Ren X, Zhang J, Lin Q, Zhao Y. Supramolecular adhesive hydrogels for tissue engineering applications. Chemical Reviews. 2022 Jan 13;122(6):5604-40. https://doi.org/10.1021/acs.chemrev.1c00815
PMid:35023737 60. Cascone S, Lamberti G. Hydrogel-based commercial products for biomedical applications: A review. International journal of pharmaceutics. 2020 Jan 5;573:118803. https://doi.org/10.1016/j.ijpharm.2019.118803 PMid:31682963
61. Sun Y, Yang C, Zhu X, Wang JJ, Liu XY, Yang XP, An XW, Liang J, Dong HJ, Jiang W, Chen C. 3D printing collagen/chitosan scaffold ameliorated axon regeneration and neurological recovery after spinal cord injury. Journal of Biomedical Materials Research Part A. 2019 Sep;107(9):1898-908. https://doi.org/10.1002/jbm.a.36675 PMid:30903675
62. Ning L, Zhu N, Mohabatpour F, Sarker MD, Schreyer DJ, Chen X. Bioprinting Schwann cell-laden scaffolds from low-viscosity hydrogel compositions. Journal of Materials Chemistry B. 2019;7(29):4538-51. https://doi.org/10.1039/C9TB00669A
63. Loh EY, Mohamad N, Fauzi MB, Ng MH, Ng SF, Mohd Amin MC. Development of a bacterial cellulose-based hydrogel cell carrier containing keratinocytes and fibroblasts for full-thickness wound healing. Scientific Reports. 2018 Feb 13;8(1):2875. https://doi.org/10.1038/s41598-018-21174-7 PMid:29440678 PMCid:PMC5811544
64. Li J, Zhang D, Guo S, Zhao C, Wang L, Ma S, Guan F, Yao M. Dual-enzymatically cross-linked gelatin hydrogel promotes neural differentiation and neurotrophin secretion of bone marrow-derived mesenchymal stem cells for treatment of moderate traumatic brain injury. International Journal of Biological Macromolecules. 2021 Sep 30;187:200-13. https://doi.org/10.1016/j.ijbiomac.2021.07.111 PMid:34310990
65. Chung TW, Chen WP, Tai PW, Lo HY, Wu TY. Roles of silk fibroin on characteristics of hyaluronic acid/silk fibroin hydrogels for tissue engineering of nucleus pulposus. Materials. 2020 Jun 17;13(12):2750. https://doi.org/10.3390/ma13122750 PMid:32560556 PMCid:PMC7345670
66. Finklea FB, Tian Y, Kerscher P, Seeto WJ, Ellis ME, Lipke EA. Engineered cardiac tissue microsphere production through direct differentiation of hydrogel-encapsulated human pluripotent stem cells. Biomaterials. 2021 Jul 1;274:120818. https://doi.org/10.1016/j.biomaterials.2021.120818 PMid:34023620
67. Kim KS, Joo HJ, Choi SC, Kim JH, Park CY, Song MH, Noh JM, Cha JJ, Hong SJ, Ahn TH, Kim MN. Transplantation of 3D bio-printed cardiac mesh improves cardiac function and vessel formation via ANGPT1/Tie2 pathway in rats with acute myocardial infarction. Biofabrication. 2021 Aug 31;13(4):045014. https://doi.org/10.1088/1758-5090/ac1e78 PMid:34404035
68. Hu YF, Lee AS, Chang SL, Lin SF, Weng CH, Lo HY, Chou PC, Tsai YN, Sung YL, Chen CC, Yang RB. Biomaterial-induced conversion of quiescent cardiomyocytes into pacemaker cells in rats. Nature Biomedical Engineering. 2022 Apr;6(4):421-34. https://doi.org/10.1038/s41551-021-00812-y PMid:34811487
69. Park Y, Huh KM, Kang SW. Applications of biomaterials in 3D cell culture and contributions of 3D cell culture to drug development and basic biomedical research. International Journal of Molecular Sciences. 2021 Mar 2;22(5):2491. https://doi.org/10.3390/ijms22052491 PMid:33801273 PMCid:PMC7958286
70. Jose G, Shalumon KT, Chen JP. Natural polymers based hydrogels for cell culture applications. Current Medicinal Chemistry. 2020 May 1;27(16):2734-76. https://doi.org/10.2174/0929867326666190903113004 PMid:31480996
71. Cui ZK, Li SY, Liao K, Wang ZJ, Guo YL, Tang LS, Tang SB, Ma JH, Chen JS. Characteristics of neural growth and cryopreservation of the dorsal root ganglion using three-dimensional collagen hydrogel culture versus conventional culture. Neural regeneration research. 2021 Sep 1;16(9):1856-64. https://doi.org/10.4103/1673-5374.306097 PMid:33510093 PMCid:PMC8328787
72. Price RD, Berry MG, Navsaria HA. Hyaluronic acid: the scientific and clinical evidence. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2007 Oct 1;60(10):1110-9. https://doi.org/10.1016/j.bjps.2007.03.005 PMid:17466613
73. Eyrich D, Brandl F, Appel B, Wiese H, Maier G, Wenzel M, Staudenmaier R, Goepferich A, Blunk T. Long-term stable fibrin gels for cartilage engineering. Biomaterials. 2007 Jan 1;28(1):55-65. https://doi.org/10.1016/j.biomaterials.2006.08.027 PMid:16962167
74. Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Progress in polymer science. 2012 Jan 1;37(1):106-26. https://doi.org/10.1016/j.progpolymsci.2011.06.003 PMid:22125349 PMCid:PMC3223967
75. Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature. 2019 Jul 4;571(7763):117-21. https://doi.org/10.1038/s41586-019-1244-x PMid:31142833 PMCid:PMC7006049
76. Kamatar A, Gunay G, Acar H. Natural and synthetic biomaterials for engineering multicellular tumor spheroids. Polymers. 2020 Oct 28;12(11):2506. https://doi.org/10.3390/polym12112506 PMid:33126468 PMCid:PMC7692845
77. Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules. 2000 Mar 14;1(1):31-8. https://doi.org/10.1021/bm990017d PMid:11709840
78. Efron, N. and S. Efron, Therapeutic applications. Contact Lens Practice E-Book, 2016: p. 275. https://doi.org/10.1016/B978-0-7020-6660-3.00029-0
79. Otto W, Drahoslav L, inventors. Cross-linked hydrophilic polymers and articles made therefrom. United States patent US 3,220,960. 1965 Nov 30.
80. Efron N, Nichols JJ, Woods CA, Morgan PB. Trends in US contact lens prescribing 2002 to 2014. Optometry and Vision Science. 2015 Jul 1;92(7):758-67. https://doi.org/10.1097/OPX.0000000000000623 PMid:26101823
81. Caccavo D, Cascone S, Lamberti G, Barba AA. Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour. Chemical Society Reviews. 2018;47(7):2357-73. https://doi.org/10.1039/C7CS00638A PMid:29504613
82. Tranoudis I, Efron N. Tensile properties of soft contact lens materials. Contact Lens and Anterior Eye. 2004 Dec 1;27(4):177-91. https://doi.org/10.1016/j.clae.2004.08.002 PMid:16303541
83. Stapleton F, Tan J. Impact of contact lens material, design, and fitting on discomfort. Eye & contact lens. 2017 Jan 1;43(1):32-9. https://doi.org/10.1097/ICL.0000000000000318 PMid:28002225
84. Orsborn G, Vega J, Diamanti S. Impact of lens physical properties on wearer preferences after 4 weeks of daily wear in a first and third generation silicone hydrogel contact lens. Contact Lens and Anterior Eye. 2018 Jun 1;41:S59. https://doi.org/10.1016/j.clae.2018.03.053
85. Nicolson PC, Vogt J. Soft contact lens polymers: an evolution. Biomaterials. 2001 Dec 15;22(24):3273-83. https://doi.org/10.1016/S0142-9612(01)00165-X PMid:11700799
86. Lee SM, Han N, Lee R, Choi IH, Park YB, Shin JS, Yoo KH. Real-time monitoring of 3D cell culture using a 3D capacitance biosensor. Biosensors and Bioelectronics. 2016 Mar 15;77:56-61. https://doi.org/10.1016/j.bios.2015.09.005 PMid:26386332
87. Devadhasan JP, Kim S. An ultrasensitive method of real time pH monitoring with complementary metal oxide semiconductor image sensor. Analytica chimica acta. 2015 Feb 9;858:55-9. https://doi.org/10.1016/j.aca.2014.12.015 PMid:25597802
88. Hoogstraate JA, Wertz PW. Drug delivery via the buccal mucosa. Pharmaceutical Science & Technology Today. 1998 Oct 1;1(7):309-16. https://doi.org/10.1016/S1461-5347(98)00076-5
89. Hao, J. and P.W. Heng, Buccal delivery systems. Drug development and industrial pharmacy, 2003. 29(8): p. 821-832 https://doi.org/10.1081/DDC-120024178 PMid:14570303
90. Caccavo D, Lamberti G, Cascone S, Barba AA, Larsson A. Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment. Carbohydrate Polymers. 2015 Oct 20;131:41-9. https://doi.org/10.1016/j.carbpol.2015.05.041 PMid:26256158
91. Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery-a promising option for orally less efficient drugs. Journal of controlled release. 2006 Aug 10;114(1):15-40. https://doi.org/10.1016/j.jconrel.2006.04.012 PMid:16828915
92. Rizwan M, Yahya R, Hassan A, Yar M, Azzahari AD, Selvanathan V, Sonsudin F, Abouloula CN. pH sensitive hydrogels in drug delivery: Brief history, properties, swelling, and release mechanism, material selection and applications. Polymers. 2017 Apr 12;9(4):137. https://doi.org/10.3390/polym9040137 PMid:30970818 PMCid:PMC6432076
93. Goldberg M, Gomez-Orellana I. Challenges for the oral delivery of macromolecules. Nature reviews Drug discovery. 2003 Apr 1;2(4):289-95. https://doi.org/10.1038/nrd1067 PMid:12669028
94. Langer RS, Wise DL. Medical applications of controlled release. Boca Raton, FL, USA:: CRC Press LLC; 2019 Jun 4. https://doi.org/10.1201/9780429276620
95. Sharpe LA, Daily AM, Horava SD, Peppas NA. Therapeutic applications of hydrogels in oral drug delivery. Expert opinion on drug delivery. 2014 Jun 1;11(6):901-15. https://doi.org/10.1517/17425247.2014.902047 PMid:24848309 PMCid:PMC4549393
96. Gao X, Cao Y, Song X, Zhang Z, Zhuang X, He C, Chen X. Biodegradable, p H‐R esponsive Carboxymethyl Cellulose/P oly (A crylic Acid) Hydrogels for Oral Insulin Delivery. Macromolecular bioscience. 2014 Apr;14(4):565-75. https://doi.org/10.1002/mabi.201300384 PMid:24357554
97. Cascone S, Dalmoro A, Lamberti G, Titomanlio G, d'Amore M, Barba AA. In vitro simulation of human digestion: chemical and mechanical behavior. Dissolution Technologies. 2016 Nov 1;23(4):16-23. https://doi.org/10.14227/DT230416P16
98. Liu Z, Wei J, Faraj Y, Ju XJ, Xie R, Wang W, Chu LY. Smart hydrogels: Network design and emerging applications. The Canadian Journal of Chemical Engineering. 2018 Oct;96(10):2100-14. https://doi.org/10.1002/cjce.23328
99. Yang WW, Pierstorff E. Reservoir-based polymer drug delivery systems. Journal of laboratory automation. 2012 Feb;17(1):50-8. https://doi.org/10.1177/2211068211428189 PMid:22357608
100. Caramella CM, Rossi S, Ferrari F, Bonferoni MC, Sandri G. Mucoadhesive and thermogelling systems for vaginal drug delivery. Advanced drug delivery reviews. 2015 Sep 15;92:39-52. https://doi.org/10.1016/j.addr.2015.02.001 PMid:25683694
101. Valenta C. The use of mucoadhesive polymers in vaginal delivery. Advanced drug delivery reviews. 2005 Nov 3;57(11):1692-712. https://doi.org/10.1016/j.addr.2005.07.004 PMid:16182407
102. Prausnitz MR. Microneedles for transdermal drug delivery. Advanced drug delivery reviews. 2004 Mar 27;56(5):581-7. https://doi.org/10.1016/j.addr.2003.10.023 PMid:15019747
103. Prausnitz MR, Langer R. Transdermal drug delivery. Nature biotechnology. 2008 Nov;26(11):1261-8. https://doi.org/10.1038/nbt.1504 PMid:18997767 PMCid:PMC2700785
104. Kong BJ, Kim A, Park SN. Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin. Carbohydrate polymers. 2016 Aug 20;147:473-81. https://doi.org/10.1016/j.carbpol.2016.04.021 PMid:27178954
105. Srivastava R, Pathak K. An updated patent review on ocular drug delivery systems with potential for commercial viability. Recent patents on drug delivery & formulation. 2011 May 1;5(2):146-62. https://doi.org/10.2174/187221111795471436 PMid:21453249
106. Kirchhof S, Goepferich AM, Brandl FP. Hydrogels in ophthalmic applications. European Journal of Pharmaceutics and Biopharmaceutics. 2015 Sep 1;95:227-38. https://doi.org/10.1016/j.ejpb.2015.05.016 PMid:26032290
107. Mandal A, Pal D, Agrahari V, Trinh HM, Joseph M, Mitra AK. Ocular delivery of proteins and peptides: Challenges and novel formulation approaches. Advanced drug delivery reviews. 2018 Feb 15;126:67-95. https://doi.org/10.1016/j.addr.2018.01.008 PMid:29339145 PMCid:PMC5995646
108. https://g.co/about/u7gzf5109
109. Liu S, Guo R, Li C, Lu C, Yang G, Wang F, Nie J, Ma C, Gao M. POSS hybrid hydrogels: A brief review of synthesis, properties and applications. European Polymer Journal. 2021 Jan 15;143:110180. https://doi.org/10.1016/j.eurpolymj.2020.110180
110. Jacob S, Nair AB, Shah J, Sreeharsha N, Gupta S, Shinu P. Emerging role of hydrogels in drug delivery systems, tissue engineering and wound management. Pharmaceutics. 2021 Mar 8;13(3):357. https://doi.org/10.3390/pharmaceutics13030357 PMid:33800402 PMCid:PMC7999964
111. Hu C, Zhang F, Long L, Kong Q, Luo R, Wang Y. Dual-responsive injectable hydrogels encapsulating drug-loaded micelles for on-demand antimicrobial activity and accelerated wound healing. Journal of Controlled Release. 2020 Aug 10;324:204-17. https://doi.org/10.1016/j.jconrel.2020.05.010 PMid:32389779
112. Mandal, A., et al., Hydrogels in the clinic. Bioeng Transl Med 2020;5(2):e10158. https://doi.org/10.1002/btm2.10158 PMid:32440563 PMCid:PMC7237140
113. Kong L, Wu Z, Zhao H, Cui H, Shen J, Chang J, Li H, He Y. Bioactive injectable hydrogels containing desferrioxamine and bioglass for diabetic wound healing. ACS applied materials & interfaces. 2018 Aug 16;10(36):30103-14. https://doi.org/10.1021/acsami.8b09191 PMid:30113159
114. Lee JH. Injectable hydrogels delivering therapeutic agents for disease treatment and tissue engineering. Biomaterials research. 2018 Sep 26;22(1):27. https://doi.org/10.1186/s40824-018-0138-6 PMid:30275970 PMCid:PMC6158836
115. Mandal A, Clegg JR, Anselmo AC, Mitragotri S. Hydrogels in the clinic. Bioeng Transl Med 2020;5(2):e10158. https://doi.org/10.1002/btm2.10158 PMid:32440563 PMCid:PMC7237140
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