Crosslinked natural hydrogels for drug delivery systems en en Hydrogels made from a variety of materials may be used as a novel technology in regenerative medicine in the biomedical field. Hydrogels may be made using both chemical and physical processes, depending on the source material. Size, elastic modulus, swelling, and degradation rate are only a few of the many physical parameters that may be used to define hydrogels in experiments. Hydrogels made from natural polymers have been the focus of our review. Due to their remarkable biocompatibility and nontoxicity, simple gelation, and functionalization, hydrogels derived from natural polymers have received extensive attention in recent decades. As a result, natural polymer hydrogels are considered excellent biomaterials that have great potential in the biomedical field. Because carriers play such a large role in determining how far and how fast drugs reach their intended recipients, the need for intelligent drug delivery systems (DDSs) is on the rise. An outstanding goal of this study is to examine the impact that various crosslinking process parameters have on the drug delivery mechanism. 109 123 Akram Noori Tahneh Department of Pharmaceutical Chemistry Pharmaceutical Science Branch, Islamic Azad University Iran info@jourcc.com Bahareh Dashtipour Department of Chemistry Alzahra University Iran info@jourcc.com Alireza Ghofrani Department of Biomedical Engineering Amirkabir University of Technology Iran alirezaqofrani@gmail.com Somayeh Keramati Nejad Clinical Research Development Unit of Razi Hospital Birjand University of Medical Science Iran info@jourcc.com Natural hydrogels Crosslinking Drug delivery mechanisms Article6.pdf [1] W.B. Liechty, D.R. Kryscio, B.V. Slaughter, N.A. Peppas, Polymers for drug delivery systems, Annual review of chemical and biomolecular engineering 1 (2010) 149-173. ## [2] M. Alizadeh, M. Paydar, F.S. Jazi, Structural evaluation and mechanical prop-erties of nanostructured Al/B4C composite fabricated by ARB process, Composites Part B: Engineering 44(1) (2013) 339-343. ## [3] F. Sharifianjazi, A.J. Rad, A. Esmaeilkhanian, F. Niazvand, A. Bakhtiari, L. Ba-zli, M. Abniki, M. Irani, A. Moghanian, Biosensors and nanotechnology for cancer diagnosis (lung and bronchus, breast, prostate, and colon): A systematic review, Biomedical Materials (2021). ## [4] V.P.S. Sidhu, R. Borges, M. Yusuf, S. Mahmoudi, S.F. Ghorbani, M. Hosseini-kia, P. Salahshour, F. Sadeghi, M. Arefian, A comprehensive review of bioactive glass: synthesis, ion substitution, application, challenges, and future perspectives, Journal of Composites and Compounds 3(9) (2021) 247-261. ## [5] M.S. Alqahtani, M. Kazi, M.A. Alsenaidy, M.Z. Ahmad, Advances in oral drug delivery, Frontiers in Pharmacology 12 (2021) 618411. ## [6] M.W. Tibbitt, J.E. Dahlman, R. Langer, Emerging frontiers in drug delivery, Journal of the American Chemical Society 138(3) (2016) 704-717. ## [7] G. Tiwari, R. Tiwari, B. Sriwastawa, L. Bhati, S. Pandey, P. Pandey, S.K. Ban-nerjee, Drug delivery systems: An updated review, International journal of phar-maceutical investigation 2(1) (2012) 2. ## [8] D.F.A. Loghin, G. Biliuta, S. Coseri, E.S. Dragan, Preparation and characteri-zation of oxidized starch/poly (N, N-dimethylaminoethyl methacrylate) semi-IPN cryogels and in vitro controlled release evaluation of indomethacin, International journal of biological macromolecules 96 (2017) 589-599. ## [9] M. Farokhi, F. Mottaghitalab, M.A. Shokrgozar, K.-L. Ou, C. Mao, H. Hos-seinkhani, Importance of dual delivery systems for bone tissue engineering, Jour-nal of Controlled Release 225 (2016) 152-169. ## [10] Z. Goudarzi, N. Parvin, F. Sharifianjazi, Formation of hydroxyapatite on sur-face of SiO2–P2O5–CaO–SrO–ZnO bioactive glass synthesized through sol-gel route, Ceramics International 45(15) (2019) 19323-19330. ## [11] F. Sharifianjazi, P. Zeydi, M. Bazli, A. Esmaeilkhanian, R. Rahmani, L. Bazli, S. Khaksar, Fibre-Reinforced Polymer Reinforced Concrete Members under Ele-vated Temperatures: A Review on Structural Performance, Polymers 14(3) (2022) 472. ## [12] X. Qi, L. Lin, L. Shen, Z. Li, T. Qin, Y. Qian, X. Wu, X. Wei, Q. Gong, J. Shen, Efficient decontamination of lead ions from wastewater by salecan polysac-charide-based hydrogels, ACS Sustainable Chemistry & Engineering 7(12) (2019) 11014-11023. ## [13] X. Qi, W. Wei, J. Li, Y. Liu, X. Hu, J. Zhang, L. Bi, W. Dong, Fabrication and characterization of a novel anticancer drug delivery system: salecan/poly (meth-acrylic acid) semi-interpenetrating polymer network hydrogel, ACS Biomaterials Science & Engineering 1(12) (2015) 1287-1299. ## [14] X. Qi, W. Wei, J. Li, T. Su, X. Pan, G. Zuo, J. Zhang, W. Dong, Design of Salecan-containing semi-IPN hydrogel for amoxicillin delivery, Materials Science and Engineering: C 75 (2017) 487-494. ## [15] E.S. Dragan, A.I. Cocarta, Smart macroporous IPN hydrogels responsive to pH, temperature, and ionic strength: synthesis, characterization, and evaluation of controlled release of drugs, ACS applied materials & interfaces 8(19) (2016)12018-12030. ## [16] M.M. Lazar, I.A. Dinu, M. Silion, E.S. Dragan, M.V. Dinu, Could the porous chitosan-based composite materials have a chance to a “NEW LIFE” after Cu (II) ion binding?, International journal of biological macromolecules 131 (2019) 134-146. ## [17] E.S. Dragan, D. Humelnicu, M.V. Dinu, Development of chitosan-poly (eth-yleneimine) based double network cryogels and their application as superadsor-bents for phosphate, Carbohydrate polymers 210 (2019) 17-25. ## [18] E.S. Dragan, D. Humelnicu, M.V. Dinu, R.I. Olariu, Kinetics, equilibrium modeling, and thermodynamics on removal of Cr (VI) ions from aqueous solution using novel composites with strong base anion exchanger microspheres embed-ded into chitosan/poly (vinyl amine) cryogels, Chemical Engineering Journal 330 (2017) 675-691. ## [19] F. Sharifianjazi, S. Khaksar, A. Esmaeilkhanian, L. Bazli, S. Eskandarinezhad, P. Salahshour, F. Sadeghi, S. Rostamnia, S.M. Vahdat, Advancements in Fabrica-tion and Application of Chitosan Composites in Implants and Dentistry: A Review, Biomolecules 12(2) (2022) 155. ## [20] F. Sharifianjazi, A. Esmaeilkhanian, M. Moradi, A. Pakseresht, M.S. Asl, H. Karimi-Maleh, H.W. Jang, M. Shokouhimehr, R.S. Varma, Biocompatibility and mechanical properties of pigeon bone waste extracted natural nano-hydroxyapa-tite for bone tissue engineering, Materials Science and Engineering: B 264 (2021) 114950. ## [21] R. Alisani, N. Rakhshani, M. Abolhallaj, F. Motevalli, P.G.-s. Abadi, M. Akra-mi, M. Shahrousvand, F.S. Jazi, M. Irani, Adsorption, and controlled release of doxorubicin from cellulose acetate/polyurethane/multi-walled carbon nanotubes composite nanofibers, Nanotechnology 33(15) (2022) 155102. ## [22] X. Qi, Y. Yuan, J. Zhang, J.W. Bulte, W. Dong, Oral administration of sale-can-based hydrogels for controlled insulin delivery, Journal of agricultural and food chemistry 66(40) (2018) 10479-10489. ## [23] J. Chen, J. Ouyang, Q. Chen, C. Deng, F. Meng, J. Zhang, R. Cheng, Q. Lan, Z. Zhong, EGFR and CD44 dual-targeted multifunctional hyaluronic acid nano-gels boost protein delivery to ovarian and breast cancers in vitro and in vivo, ACS applied materials & interfaces 9(28) (2017) 24140-24147. ## [24] F.S. Rezaei, F. Sharifianjazi, A. Esmaeilkhanian, E. Salehi, Chitosan films and scaffolds for regenerative medicine applications: A review, Carbohydrate polymers 273 (2021) 118631. ## [25] T. RAO, P. CHVS, Hydrogels the three dimensional networks: a review, Int J Curr Pharm Res 13(1) (2021) 12-17. ## [26] F. Wang, Y. Zhang, Y. Wang, Recycling of Waste Cotton Sheets into Three-Di-mensional Biodegradable Carriers for Removal of Methylene Blue, ACS omega 6(50) (2021) 34314-34326. ## [27] Y. Fang, N. Qiao, H. Deng, M. Ren, Y. Zhang, D. Zhang, H. Lin, Y. Chen, K.T. Yong, J. Xiong, PEDOT: PSS‐Based Microfluidic‐Spun Microfibers for Tunable Release of Acetaminophen via Electrical Stimulation, Advanced Materials Tech-nologies 2200103. ## [28] V. Manish, K.V. Siva, A. Arockiarajan, G. Tamadapu, Synthesis and character-ization of hard magnetic soft hydrogels, Materials Letters (2022) 132323. ## [29] H. Lu, X. Li, H. Yang, J. Wu, Y. Zhang, H. Huang, Preparation and proper-ties of riboflavin-loaded sanxan microcapsules, Food Hydrocolloids 129 (2022) 107641. ## [30] M.J. Monteiro, M.F. Cunningham, Polymer Colloids: Synthesis Fundamentals to Applications, ACS Publications, 2020, pp. 4377-4378. ## [31] J. Lu, Y. Li, H. Zhu, G. Shi, SiO2-Coated Fe3O4 Nanoparticle/Polyacryloni-trile Beads for One-Step Lipase Immobilization, ACS Applied Nano Materials 4(8) (2021) 7856-7869. ## [32] D.M. Nascimento, Y.L. Nunes, M.C. Figueirêdo, H.M. de Azeredo, F.A. Aouada, J.P. Feitosa, M.F. Rosa, A. Dufresne, Nanocellulose nanocomposite hy-drogels: technological and environmental issues, Green Chemistry 20(11) (2018) 2428-2448. ## [33] F. Sharifianjazi, M. Irani, A. Esmaeilkhanian, L. Bazli, M.S. Asl, H.W. Jang, S.Y. Kim, S. Ramakrishna, M. Shokouhimehr, R.S. Varma, Polymer incorporated magnetic nanoparticles: Applications for magnetoresponsive targeted drug deliv-ery, Materials Science and Engineering: B 272 (2021) 115358. ## [34] H.N. Abdelhamid, A.P. Mathew, Cellulose-Based Nanomaterials Advance Biomedicine: A Review, International Journal of Molecular Sciences 23(10) (2022) 5405. ## [35] J. Liao, B. Hou, H. Huang, Preparation, properties and drug controlled release of chitin-based hydrogels: An updated review, Carbohydrate Polymers (2022) 119177. ## [36] L. Lei, Y. Bai, X. Qin, J. Liu, W. Huang, Q. Lv, Current Understanding of Hydrogel for Drug Release and Tissue Engineering, Gels 8(5) (2022) 301. ## [37] B. Fu, H.-C. Lin, N. Chen, P. Zhao, Adenosine triphosphate/pH dual-respon-sive controlled drug release system with high cancer/normal cell selectivity and low side toxicity, Journal of Biomaterials Applications (2022) 08853282221087412. ## [38] A. Bordbar-Khiabani, M. Gasik, Smart Hydrogels for Advanced Drug De-livery Systems, International Journal of Molecular Sciences 23(7) (2022) 3665. ## [39] E.R. Aluri, E. Gannon, K. Singh, S. Kolagatla, K. Kowiorski, S. Shingte, E. McKiernan, C. Moloney, K. McGarry, L. Jowett, Graphene oxide modulates inter-particle interactions in 3D printable soft nanocomposite hydrogels restoring magnetic hyperthermia responses, Journal of Colloid and Interface Science 611 (2022) 533-544. ## [40] N. Reddy, R. Reddy, Q. Jiang, Crosslinking biopolymers for biomedical appli-cations, Trends in biotechnology 33(6) (2015) 362-369. ## [41] A.W. Martinez, J.M. Caves, S. Ravi, W. Li, E.L. Chaikof, Effects of cross-linking on the mechanical properties, drug release and cytocompatibility of protein polymers, Acta biomaterialia 10(1) (2014) 26-33. ## [42] S. Zhai, X. Hu, Y. Hu, B. Wu, D. Xing, Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy, Biomaterials 121 (2017) 41-54. ## [43] M. Radmansouri, E. Bahmani, E. Sarikhani, K. Rahmani, F. Sharifianjazi, M. Irani, Doxorubicin hydrochloride-Loaded electrospun chitosan/cobalt ferrite/tita-nium oxide nanofibers for hyperthermic tumor cell treatment and controlled drug release, International journal of biological macromolecules 116 (2018) 378-384. ## [44] P. Abasian, M. Radmansouri, M.H. Jouybari, M.V. Ghasemi, A. Mohammadi, M. Irani, F.S. Jazi, Incorporation of magnetic NaX zeolite/DOX into the PLA/chi-tosan nanofibers for sustained release of doxorubicin against carcinoma cells death in vitro, International journal of biological macromolecules 121 (2019) 398-406. ## [45] W.E. Hennink, C.F. van Nostrum, Novel crosslinking methods to design hy-drogels, Advanced drug delivery reviews 64 (2012) 223-236. ## [46] M. Ermis, S. Calamak, G.C. Kocal, S. Guven, N.G. Durmus, I. Rizvi, T. Hasan, N. Hasirci, V. Hasirci, U. Demirci, Hydrogels as a new platform to recapit-ulate the tumor microenvironment, Handbook of nanomaterials for cancer thera-nostics, Elsevier2018, pp. 463-494. ## [47] Y. Su, T. Feng, W. Feng, Y. Pei, Z. Li, J. Huo, C. Xie, X. Qu, P. Li, W. Huang, Mussel‐inspired, surface‐attachable initiator for grafting of antimicrobial and antifouling hydrogels, Macromolecular Rapid Communications 40(17) (2019) 1900268. ## [48] P. Liu, M. Zhai, J. Li, J. Peng, J. Wu, Radiation preparation and swelling behavior of sodium carboxymethyl cellulose hydrogels, Radiation Physics and Chemistry 63(3-6) (2002) 525-528. ## [49] Y.-C. Nho, J.-H. Lee, Reduction of postsurgical adhesion formation with hydrogels synthesized by radiation, Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 236(1-4) (2005) 277-282. ## [50] T.R. Hoare, D.S. Kohane, Hydrogels in drug delivery: Progress and challeng-es, polymer 49(8) (2008) 1993-2007. ## [51] Z. Ahmad, S. Salman, S.A. Khan, A. Amin, Z.U. Rahman, Y.O. Al-Gham-di, K. Akhtar, E.M. Bakhsh, S.B. Khan, Versatility of Hydrogels: From Synthetic Strategies, Classification, and Properties to Biomedical Applications, Gels 8(3) (2022) 167. ## [52] M.S.N. Shahrbabak, F. Sharifianjazi, D. Rahban, A. Salimi, A comparative investigation on bioactivity and antibacterial properties of sol-gel derived 58S bio-active glass substituted by Ag and Zn, Silicon 11(6) (2019) 2741-2751. ## [53] L.S.M. Teixeira, J. Feijen, C.A. van Blitterswijk, P.J. Dijkstra, M. Karperien, Enzyme-catalyzed crosslinkable hydrogels: emerging strategies for tissue engi-neering, Biomaterials 33(5) (2012) 1281-1290. ## [54] S.-H. Kim, S.-H. Lee, J.-E. Lee, S.J. Park, K. Kim, I.S. Kim, Y.-S. Lee, N.S. Hwang, B.-G. Kim, Tissue adhesive, rapid forming, and sprayable ECM hydrogel via recombinant tyrosinase crosslinking, Biomaterials 178 (2018) 401-412. ## [55] K. Kim, S. Park, J.-A. Yang, J.-H. Jeon, S. Bhang, B.-S. Kim, S. Hahn, Inject-able hyaluronic acid–tyramine hydrogels for the treatment of rheumatoid arthritis, Acta biomaterialia 7(2) (2011) 666-674. ## [56] N.E. Davis, S. Ding, R.E. Forster, D.M. Pinkas, A.E. Barron, Modular enzy-matically crosslinked protein polymer hydrogels for in situ gelation, Biomaterials 31(28) (2010) 7288-7297. ## [57] C. Yung, L. Wu, J. Tullman, G. Payne, W. Bentley, T. Barbari, Transglutam-inase crosslinked gelatin as a tissue engineering scaffold, Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomateri-als and the Korean Society for Biomaterials 83(4) (2007) 1039-1046. ## [58] R. Jin, L.M. Teixeira, P.J. Dijkstra, M. Karperien, C. Van Blitterswijk, Z. Zhong, J. Feijen, Injectable chitosan-based hydrogels for cartilage tissue engineer-ing, Biomaterials 30(13) (2009) 2544-2551. ## [59] H. Samadian, H. Maleki, Z. Allahyari, M. Jaymand, Natural polymers-based light-induced hydrogels: Promising biomaterials for biomedical applications, Co-ordination Chemistry Reviews 420 (2020) 213432. ## [60] B. Li, L. Wang, F. Xu, X. Gang, U. Demirci, D. Wei, Y. Li, Y. Feng, D. Jia, Y. Zhou, Hydrosoluble, UV-crosslinkable and injectable chitosan for patterned cell-laden microgel and rapid transdermal curing hydrogel in vivo, Acta bioma-terialia 22 (2015) 59-69. ## [61] H.S. Yoo, Photo-cross-linkable and thermo-responsive hydrogels containing chitosan and Pluronic for sustained release of human growth hormone (hGH), Journal of Biomaterials Science, Polymer Edition 18(11) (2007) 1429-1441. ## [62] J. Im Lee, H.S. Kim, H.S. Yoo, DNA nanogels composed of chitosan and Pluronic with thermo-sensitive and photo-crosslinking properties, International journal of pharmaceutics 373(1-2) (2009) 93-99. ## [63] Y. Yeo, W. Geng, T. Ito, D.S. Kohane, J.A. Burdick, M. Radisic, Photocross-linkable hydrogel for myocyte cell culture and injection, Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The So-ciety for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials 81(2) (2007) 312-322. ## [64] J. Łukaszczyk, M. Śmiga, K. Jaszcz, H.J.P. Adler, E. Jähne, M. Kaczmarek, Evaluation of oligo (ethylene glycol) dimethacrylates effects on the properties of new biodegradable bone cement compositions, Macromolecular bioscience 5(1) (2005) 64-69. ## [65] C.Y. Anthony, A.A. Smith, E.A. Appel, Structural considerations for physical hydrogels based on polymer–nanoparticle interactions, Molecular Systems Design & Engineering 5(1) (2020) 401-407. ## [66] N. Bhattarai, J. Gunn, M. Zhang, Chitosan-based hydrogels for controlled, localized drug delivery, Advanced drug delivery reviews 62(1) (2010) 83-99. ## [67] C. Hiemstra, L.J. van der Aa, Z. Zhong, P.J. Dijkstra, J. Feijen, Novel in situ forming, degradable dextran hydrogels by Michael addition chemistry: synthesis, rheology, and degradation, Macromolecules 40(4) (2007) 1165-1173. ## [68] V.G. Muir, T.H. Qazi, S. Weintraub, B.O. Torres Maldonado, P.E. Arratia, J.A. Burdick, Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter‐Particle Crosslinking, Small (2022) 2201115. ## [69] J. Berger, M. Reist, J.M. Mayer, O. Felt, N. Peppas, R. Gurny, Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomed-ical applications, European journal of pharmaceutics and biopharmaceutics 57(1) (2004) 19-34. ## [70] K. Nishi, A. Jayakrishnan, Self-gelling primaquine− gum arabic conjugate: an injectable controlled delivery system for primaquine, Biomacromolecules 8(1) (2007) 84-90. ## [71] H.-F. Liang, M.-H. Hong, R.-M. Ho, C.-K. Chung, Y.-H. Lin, C.-H. Chen, H.-W. Sung, Novel method using a temperature-sensitive polymer (methylcellulose) to thermally gel aqueous alginate as a pH-sensitive hydrogel, Biomacromolecules 5(5) (2004) 1917-1925. ## [72] W.S. Shim, J.-H. Kim, K. Kim, Y.-S. Kim, R.-W. Park, I.-S. Kim, I.C. Kwon, D.S. Lee, pH-and temperature-sensitive, injectable, biodegradable block copoly-mer hydrogels as carriers for paclitaxel, International journal of pharmaceutics 331(1) (2007) 11-18. ## [73] M. Kurisawa, J.E. Chung, Y.Y. Yang, S.J. Gao, H. Uyama, Injectable biode-gradable hydrogels composed of hyaluronic acid–tyramine conjugates for drug de-livery and tissue engineering, Chemical communications (34) (2005) 4312-4314. ## [74] H.W. Sung, I.L. Liang, C.N. Chen, R.N. Huang, H.F. Liang, Stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin), Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials 55(4) (2001) 538-546. ## [75] M.F. Butler, Y.F. Ng, P.D. Pudney, Mechanism and kinetics of the crosslink-ing reaction between biopolymers containing primary amine groups and genipin, Journal of Polymer Science Part A: Polymer Chemistry 41(24) (2003) 3941-3953. ## [76] S.-C. Chen, Y.-C. Wu, F.-L. Mi, Y.-H. Lin, L.-C. Yu, H.-W. Sung, A novel pH-sensitive hydrogel composed of N, O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery, Journal of Controlled Release 96(2) (2004) 285-300. ## [77] F.-L. Mi, H.-W. Sung, S.-S. Shyu, Drug release from chitosan–alginate com-plex beads reinforced by a naturally occurring cross-linking agent, Carbohydrate Polymers 48(1) (2002) 61-72. ## [78] Z. Zou, B. Zhang, X. Nie, Y. Cheng, Z. Hu, M. Liao, S. Li, A sodium al-ginate-based sustained-release IPN hydrogel and its applications, RSC advances 10(65) (2020) 39722-39730. ## [79] S.V. Wanasinghe, E.M. Schreiber, A.M. Thompson, J.L. Sparks, D. Konkole-wicz, Dynamic covalent chemistry for architecture changing interpenetrated and single networks, Polymer Chemistry 12(13) (2021) 1975-1982. ## [80] A. Behravesh, M. Shahrousvand, A. Goudarzi, Poly (acrylic acid)/gum ara-bic/ZnO semi-IPN hydrogels: synthesis, characterization and their optimizations by response surface methodology, Iranian Polymer Journal 30(7) (2021) 655-674. ## [81] G. Somya, P. Nayyar, B. Akanksha, S.P. Kumar, Interpenetrating polymer network-based drug delivery systems: emerging applications and recent patents, Egyptian Pharmaceutical Journal 14(2) (2015) 75. ## [82] I. Ali, L. Ali Shah, S. Faizan, Investigation of the viscoelastic behavior of PVA-P (AAm/AMPS) IPN hydrogel with enhanced mechanical strength and excel-lent recoverability, Journal of Polymer Research 29(1) (2022) 1-12. ## [83] A.S. Hoffman, Hydrogels for biomedical applications, Advanced drug deliv-ery reviews 64 (2012) 18-23. ## [84] G.A. Kumar, S.A. Wadood, S.D. Maurya, D. Ramchand, Interpenetrating polymeric network hydrogel for stomach-specific drug delivery of clarithromycin: Preparation and evaluation, Asian Journal of Pharmaceutics-October-December (2010). ## [85] S.S. Vaghani, M.M. Patel, pH-sensitive hydrogels based on semi-interpene-trating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromy-cin release, Drug development and industrial pharmacy 37(10) (2011) 1160-1169. ## [86] R.V. Kulkarni, V. Sreedhar, S. Mutalik, C.M. Setty, B. Sa, Interpenetrating network hydrogel membranes of sodium alginate and poly (vinyl alcohol) for controlled release of prazosin hydrochloride through skin, International Journal of Biological Macromolecules 47(4) (2010) 520-527. ## [87] A.P. Rokhade, N.B. Shelke, S.A. Patil, T.M. Aminabhavi, Novel interpenetrat-ing polymer network microspheres of chitosan and methylcellulose for controlled release of theophylline, Carbohydrate Polymers 69(4) (2007) 678-687. ## [88] Y. Zhang, J. Liu, L. Huang, Z. Wang, L. Wang, Design and performance of a sericin-alginate interpenetrating network hydrogel for cell and drug delivery, Sci-entific reports 5(1) (2015) 1-13. ## [89] E.M. Ahmed, Hydrogel: Preparation, characterization, and applications: A review, Journal of advanced research 6(2) (2015) 105-121. ## [90] F. Ullah, M.B.H. Othman, F. Javed, Z. Ahmad, H.M. Akil, Classification, pro-cessing and application of hydrogels: A review, Materials Science and Engineer-ing: C 57 (2015) 414-433. ## [91] U. Usta, R. Asmatulu, Hydrogels in various biomedical applications, Poly-mer Science: Research Advances, Practical Applications and Educational Aspects (2015) 248-257. ## [92] A. Moghanian, A. Ghorbanoghli, M. Kazem‐Rostami, A. Pazhouheshgar, E. Salari, M. Saghafi Yazdi, T. Alimardani, H. Jahani, F. Sharifian Jazi, M. Tahriri, Novel antibacterial Cu/Mg‐substituted 58S‐bioglass: Synthesis, characterization and investigation of in vitro bioactivity, International Journal of Applied Glass Science 11(4) (2020) 685-698. ## [93] X. Liu, X. He, B. Yang, L. Lai, N. Chen, J. Hu, Q. Lu, Dual physically cross‐linked hydrogels incorporating hydrophobic interactions with promising repair-ability and ultrahigh elongation, Advanced Functional Materials 31(3) (2021) 2008187. ## [94] T. Watanabe, A. Ohtsuka, N. Murase, P. Barth, K. Gersonde, NMR studies on water and polymer diffusion in dextran gels. Influence of potassium ions on mi-crostructure formation and gelation mechanism, Magnetic resonance in medicine 35(5) (1996) 697-705. ## [95] A.V. Reis, M.R. Guilherme, O.A. Cavalcanti, A.F. Rubira, E.C. Muniz, Syn-thesis and characterization of pH-responsive hydrogels based on chemically modi-fied Arabic gum polysaccharide, Polymer 47(6) (2006) 2023-2029. ## [96] K. Varaprasad, G.M. Raghavendra, T. Jayaramudu, M.M. Yallapu, R. Sadiku, A mini review on hydrogels classification and recent developments in miscella-neous applications, Materials Science and Engineering: C 79 (2017) 958-971. ## [97] A. Esmaeilkhanian, F. Sharifianjazi, A. Abouchenari, A. Rouhani, N. Parvin, M. Irani, Synthesis and characterization of natural nano-hydroxyapatite derived from turkey femur-bone waste, Applied biochemistry and biotechnology 189(3) (2019) 919-932. ## [98] F. Sharifianjazi, N. Parvin, M. Tahriri, Synthesis and characteristics of sol-gel bioactive SiO2-P2O5-CaO-Ag2O glasses, Journal of Non-Crystalline Solids 476 (2017) 108-113. ## [99] F. Sharifianjazi, A.H. Pakseresht, M.S. Asl, A. Esmaeilkhanian, H.W. Jang, M. Shokouhimehr, Hydroxyapatite consolidated by zirconia: applications for dental implant, Journal of Composites and Compounds 2(2) (2020) 26-34. ## [100] S. De Jong, B. Van Eerdenbrugh, C.v. van Nostrum, J. Kettenes-Van Den Bosch, W. Hennink, Physically crosslinked dextran hydrogels by stereocomplex formation of lactic acid oligomers: degradation and protein release behavior, Jour-nal of controlled release 71(3) (2001) 261-275. ## [101] K. Saini, Preparation method, Properties and Crosslinking of hydrogel: a review, PharmaTutor 5(1) (2017) 27-36. ## [102] B.F. Dizaji, M.H. Azerbaijan, N. Sheisi, P. Goleij, T. Mirmajidi, F. Chogan, M. Irani, F. Sharafian, Synthesis of PLGA/chitosan/zeolites and PLGA/chitosan/metal organic frameworks nanofibers for targeted delivery of Paclitaxel toward prostate cancer cells death, International journal of biological macromolecules 164 (2020) 1461-1474. ## [103] R. Stenekes, H. Talsma, W. Hennink, Formation of dextran hydrogels by crystallization, Biomaterials 22(13) (2001) 1891-1898. ## [104] M.F. Akhtar, M. Hanif, N.M. Ranjha, Methods of synthesis of hydrogels... A review, Saudi Pharmaceutical Journal 24(5) (2016) 554-559. ## [105] M. Mihajlovic, M. Staropoli, M.-S. Appavou, H.M. Wyss, W. Pyck-hout-Hintzen, R.P. Sijbesma, Tough supramolecular hydrogel based on strong hydrophobic interactions in a multiblock segmented copolymer, Macromolecules 50(8) (2017) 3333-3346. ## [106] M.A. Haque, T. Kurokawa, G. Kamita, J.P. Gong, Lamellar bilayers as re-versible sacrificial bonds to toughen hydrogel: hysteresis, self-recovery, fatigue resistance, and crack blunting, Macromolecules 44(22) (2011) 8916-8924. ## [107] Y. Luo, Q. Wang, Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery, International journal of biological macromolecules 64 (2014) 353-367. ## [108] T. Gotoh, K. Matsushima, K.-I. Kikuchi, Preparation of alginate–chitosan hybrid gel beads and adsorption of divalent metal ions, Chemosphere 55(1) (2004) 135-140. ## [109] Y. Huang, H. Yu, C. Xiao, pH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release, Carbohydrate poly-mers 69(4) (2007) 774-783. ## [110] M. Ebara, Y. Kotsuchibashi, K. Uto, T. Aoyagi, Y.-J. Kim, R. Narain, N. Ido-ta, J.M. Hoffman, Smart nanoassemblies and nanoparticles, Smart Biomaterials, Springer2014, pp. 67-113. ## [111] S.S. Vaghani, M.M. Patel, pH-sensitive hydrogels based on semi-interpen-etrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithro-mycin release, Drug development and industrial pharmacy 37(10) (2011) 1160-9. ## [112] R.V. Kulkarni, V. Sreedhar, S. Mutalik, C.M. Setty, B. Sa, Interpenetrating network hydrogel membranes of sodium alginate and poly(vinyl alcohol) for con-trolled release of prazosin hydrochloride through skin, International journal of bi-ological macromolecules 47(4) (2010) 520-7. ## [113] T.W. Chung, S.Y. Lin, D.Z. Liu, Y.C. Tyan, J.S. Yang, Sustained release of 5-FU from Poloxamer gels interpenetrated by crosslinking chitosan network, Int J Pharm 382(1-2) (2009) 39-44. ## [114] Y. Zhang, J. Liu, L. Huang, Z. Wang, L. Wang, Design and performance of a sericin-alginate interpenetrating network hydrogel for cell and drug delivery, Scientific Reports 5(1) (2015) 12374. ## [115] C.W. Yung, L.Q. Wu, J.A. Tullman, G.F. Payne, W.E. Bentley, T.A. Barbari, Transglutaminase crosslinked gelatin as a tissue engineering scaffold, Journal of biomedical materials research. Part A 83(4) (2007) 1039-1046. ## [116] C.W. Yung, W.E. Bentley, T.A. Barbari, Diffusion of interleukin-2 from cells overlaid with cytocompatible enzyme-crosslinked gelatin hydrogels, Journal of biomedical materials research. Part A 95(1) (2010) 25-32. ## [117] K.S. Kim, S.J. Park, J.A. Yang, J.H. Jeon, S.H. Bhang, B.S. Kim, S.K. Hahn, Injectable hyaluronic acid-tyramine hydrogels for the treatment of rheumatoid ar-thritis, Acta Biomater 7(2) (2011) 666-74. ## [118] Y. Yeo, W. Geng, T. Ito, D.S. Kohane, J.A. Burdick, M. Radisic, Photocross-linkable hydrogel for myocyte cell culture and injection, Journal of biomedical materials research. Part B, Applied biomaterials 81(2) (2007) 312-22. ## [119] H.S. Yoo, Photo-cross-linkable and thermo-responsive hydrogels contain-ing chitosan and Pluronic for sustained release of human growth hormone (hGH), Journal of biomaterials science. Polymer edition 18(11) (2007) 1429-41. ## [120] J.I. Lee, H.S. Kim, H.S. Yoo, DNA nanogels composed of chitosan and Pluronic with thermo-sensitive and photo-crosslinking properties, Int J Pharm 373(1-2) (2009) 93-9. ## [121] C. Hiemstra, L.J. van der Aa, Z. Zhong, P.J. Dijkstra, J. Feijen, Novel in Situ Forming, Degradable Dextran Hydrogels by Michael Addition Chemistry: Synthesis, Rheology, and Degradation, Macromolecules 40(4) (2007) 1165-1173. ## [122] T. Ito, Y. Yeo, C.B. Highley, E. Bellas, C.A. Benitez, D.S. Kohane, The pre-vention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives, Biomaterials 28(6) (2007) 975-83. ## [123] K.Y. Lee, E. Alsberg, D.J. Mooney, Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue engineering, Journal of biomedical materials research 56(2) (2001) 228-33. ## [124] K.K. Nishi, A. Jayakrishnan, Self-gelling primaquine-gum arabic conjugate: an injectable controlled delivery system for primaquine, Biomacromolecules 8(1) (2007) 84-90. ## [125] M. Butler, Y.F. Ng, P. Pudney, Mechanism and kinetics of crosslinking reac-tion between biopolymers containing primary amine groups and genipin, Journal of Polymer Science Part A: Polymer Chemistry 41 (2003) 3941-3953. ## [126] R. Parhi, Cross-Linked Hydrogel for Pharmaceutical Applications: A Re-view, Adv Pharm Bull 7(4) (2017) 515-530. ## [127] K. Ono, Y. Saito, H. Yura, K. Ishikawa, A. Kurita, T. Akaike, M. Ishihara, Photocrosslinkable chitosan as a biological adhesive, Journal of biomedical mate-rials research 49(2) (2000) 289-95. ## [128] E.B. Denkbaş, M. Seyyal, E. Pişkin, Implantable 5-fluorouracil loaded chi-tosan scaffolds prepared by wet spinning, Journal of Membrane Science 172(1) (2000) 33-38. ## [129] J. Li, X. Li, X. Ni, X. Wang, H. Li, K.W. Leong, Self-assembled supramo-lecular hydrogels formed by biodegradable PEO–PHB–PEO triblock copolymers and α-cyclodextrin for controlled drug delivery, Biomaterials 27(22) (2006) 4132-4140. ## [130] G.W. Bos, J.J. Jacobs, J.W. Koten, S. Van Tomme, T. Veldhuis, C.F. van Nostrum, W. Den Otter, W.E. Hennink, In situ crosslinked biodegradable hydro-gels loaded with IL-2 are effective tools for local IL-2 therapy, European journal of pharmaceutical sciences : official journal of the European Federation for Pharma-ceutical Sciences 21(4) (2004) 561-7. ## [131] V. Pazos, R. Mongrain, J.C. Tardif, Polyvinyl alcohol cryogel: optimizing the parameters of cryogenic treatment using hyperelastic models, Journal of the mechanical behavior of biomedical materials 2(5) (2009) 542-9. ## [132] Meenakshi, M. Ahuja, Metronidazole loaded carboxymethyl tamarind kernel polysaccharide-polyvinyl alcohol cryogels: preparation and characterization, Int J Biol Macromol 72 (2015) 931-8. ## [133] J.H. Sung, M.R. Hwang, J.O. Kim, J.H. Lee, Y.I. Kim, J.H. Kim, S.W. Chang, S.G. Jin, J.A. Kim, W.S. Lyoo, S.S. Han, S.K. Ku, C.S. Yong, H.G. Choi, Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan, Int J Pharm 392(1-2) (2010) 232-40. ## [134] O.M. Păduraru, D. Ciolacu, R.N. Darie, C. Vasile, Synthesis and characteri-zation of polyvinyl alcohol/cellulose cryogels and their testing as carriers for a bio-active component, Materials Science and Engineering: C 32(8) (2012) 2508-2515. ## [135] J. You, S. Xie, J. Cao, H. Ge, M. Xu, L. Zhang, J. Zhou, Quaternized Chi-tosan/Poly(acrylic acid) Polyelectrolyte Complex Hydrogels with Tough, Self-Re-covery, and Tunable Mechanical Properties, Macromolecules 49(3) (2016) 1049-1059. ## [136] P.C. Chen, Y.J. Park, L.C. Chang, D.S. Kohane, R.H. Bartlett, R. Langer, V.C. Yang, Injectable microparticle-gel system for prolonged and localized lido-caine release. I. In vitro characterization, Journal of biomedical materials research. Part A 70(3) (2004) 412-9. ## [137] Q.L. Li, Z.Q. Chen, B.W. Darvell, L.K. Liu, H.B. Jiang, Q. Zen, Q. Peng, G.M. Ou, Chitosan-phosphorylated chitosan polyelectrolyte complex hydrogel as an osteoblast carrier, Journal of biomedical materials research. Part B, Applied biomaterials 82(2) (2007) 481-6. ## [138] D. Kulig, A. Zimoch-Korzycka, A. Jarmoluk, K. Marycz, Study on Alginate⁻Chitosan Complex Formed with Different Polymers Ratio, Polymers 8(5) (2016) 167. ## [139] J. Antunes, R. Gonçalves, B. Ma, Chitosan/Poly(γ-glutamic acid) Polyelec-trolyte Complexes: From Self- Assembly to Application in Biomolecules Delivery and Regenerative Medicine, Research & Reviews: Journal of Material Sciences 04 (2016) . ## [140] S.R. Derkach, N.G. Voron’ko, N.I. Sokolan, The rheology of hydrogels based on chitosan–gelatin (bio)polyelectrolyte complexes, Journal of Dispersion Science and Technology 38(10) (2017) 1427-1434. ## [141] Saleem, R.V. Kulkarni, N.G. Patil, Formulation and Evaluation of Chitosan Based Polyelectrolyte Complex Hydrogels for Extended Release of Metoprolol Tartrate, 2011. ## [142] H.F. Liang, M.H. Hong, R.M. Ho, C.K. Chung, Y.H. Lin, C.H. Chen, H.W. Sung, Novel method using a temperature-sensitive polymer (methylcellulose) to thermally gel aqueous alginate as a pH-sensitive hydrogel, Biomacromolecules 5(5) (2004) 1917-25. ## [143] N. Bhattarai, H.R. Ramay, J. Gunn, F.A. Matsen, M. Zhang, PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release, Journal of controlled release : official journal of the Controlled Release Society 103(3) (2005) 609-24. ## [144] J.W. Bae, D.H. Go, K.D. Park, S.J. Lee, Thermosensitive chitosan as an injectable carrier for local drug delivery, Macromolecular Research 14(4) (2006) 461-465. ## [145] M. El-Badry, G. Fetih, D. Fathalla, F. Shakeel, Transdermal delivery of meloxicam using niosomal hydrogels: in vitro and pharmacodynamic evaluation, Pharmaceutical development and technology 20(7) (2015) 820-826. ## [146] S.J. Buwalda, K.W.M. Boere, P.J. Dijkstra, J. Feijen, T. Vermonden, W.E. Hennink, Hydrogels in a historical perspective: From simple networks to smart materials, Journal of Controlled Release 190 (2014) 254-273. ## [147] S. Khan, N.M. Ranjha, Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly (vinyl alcohol) hydrogels, Polymer bulletin 71(8) (2014) 2133-2158 ## [148] V.H. Pérez-Luna, O. González-Reynoso, Encapsulation of biological agents in hydrogels for therapeutic applications, Gels 4(3) (2018) 61. ## [149] A. Onaciu, R.A. Munteanu, A.I. Moldovan, C.S. Moldovan, I. Berin-dan-Neagoe, Hydrogels based drug delivery synthesis, characterization and ad-ministration, Pharmaceutics 11(9) (2019) 432. ## [150] B. Mishra, M. Upadhyay, S. Reddy Adena, B. Vasant, M. Muthu, Hydrogels: an introduction to a controlled drug delivery device, synthesis and application in drug delivery and tissue engineering, Austin J Biomed Eng 4(1) (2017) 1037-1049. ## [151] J. Blöhbaum, I. Paulus, A.-C. Pöppler, J. Tessmar, J. Groll, Influence of charged groups on the cross-linking efficiency and release of guest molecules from thiol–ene cross-linked poly (2-oxazoline) hydrogels, Journal of materials chemis-try B 7(10) (2019) 1782-1794. ## [152] M. Mahinroosta, Z. Jomeh Farsangi, A. Allahverdi, Z. Shakoori, Hydrogels as intelligent materials: A brief review of synthesis, properties and applications, Materials Today Chemistry 8 (2018) 42-55. ## [153] M. Rizwan, R. Yahya, A. Hassan, M. Yar, A.D. Azzahari, V. Selvanathan, F. Sonsudin, C.N. Abouloula, pH Sensitive Hydrogels in Drug Delivery: Brief Histo-ry, Properties, Swelling, and Release Mechanism, Material Selection and Applica-tions, Polymers 9(4) (2017) 137. ## [154] Y. Huang, Z. Lin, M. Zheng, T. Wang, J. Yang, F. Yuan, X. Lu, L. Liu, D.J.J.o.P.S. Sun, Amorphous Fe2O3 nanoshells coated on carbonized bacterial cel-lulose nanofibers as a flexible anode for high-performance lithium ion batteries, 307 (2016) 649-656. ## [155] M.B. Rahmany, M. Van Dyke, Biomimetic approaches to modulate cellular adhesion in biomaterials: A review, Acta biomaterialia 9(3) (2013) 5431-5437. ## [156] M.M. Talukdar, I. Vinckier, P. Moldenaers, R. Kinget, Rheological char-acterization of xanthan gum and hydroxypropylmethyl cellulose with respect to controlled‐release drug delivery, Journal of pharmaceutical sciences 85(5) (1996) 537-540. ## [157] S. Khan, A. Ullah, K. Ullah, N.-u. Rehman, Insight into hydrogels, Designed monomers and polymers 19(5) (2016) 456-478. ## [158] K.V.H. Prashanth, R.N. Tharanathan, Crosslinked chitosan—preparation and characterization, Carbohydrate research 341(1) (2006) 169-173. ## [159] Y.P. Singh, N. Bhardwaj, B.B. Mandal, Potential of agarose/silk fibroin blended hydrogel for in vitro cartilage tissue engineering, ACS Applied Materials & Interfaces 8(33) (2016) 21236-21249. ## [160] Z. Mohamadnia, M. Zohuriaan-Mehr, K. Kabiri, A. Jamshidi, H. Mobedi, pH-sensitive IPN hydrogel beads of carrageenan-alginate for controlled drug de-livery, Journal of Bioactive and Compatible Polymers 22(3) (2007) 342-356. ## [161] L. Yin, L. Fei, F. Cui, C. Tang, C. Yin, Superporous hydrogels containing poly (acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks, Biomaterials 28(6) (2007) 1258-1266. ## [162] S. Li, Y. Yang, X. Yang, H. Xu, In vitro degradation and protein release of semi‐IPN hydrogels consisted of poly (acrylic acid‐acrylamide‐methacrylate) and amylose, Journal of applied polymer science 105(6) (2007) 3432-3438. ## [163] P. Chivukula, K. Dušek, D. Wang, M. Dušková-Smrčková, P. Kopečková, J. Kopeček, Synthesis and characterization of novel aromatic azo bond-contain-ing pH-sensitive and hydrolytically cleavable IPN hydrogels, Biomaterials 27(7) (2006) 1140-1151. ## [164] C. Alvarez-Lorenzo, A. Concheiro, A.S. Dubovik, N.V. Grinberg, T.V. Buro-va, V.Y. Grinberg, Temperature-sensitive chitosan-poly (N-isopropylacrylamide) interpenetrated networks with enhanced loading capacity and controlled release properties, Journal of Controlled Release 102(3) (2005) 629-641. ## [165] Y. Zhang, F. Wu, M. Li, E. Wang, pH switching on-off semi-IPN hydrogel based on cross-linked poly (acrylamide-co-acrylic acid) and linear polyallyamine, Polymer 46(18) (2005) 7695-7700. ## [166] E. Ruel-Gariepy, J.-C. Leroux, In situ-forming hydrogels—review of tem-perature-sensitive systems, European Journal of Pharmaceutics and Biopharma-ceutics 58(2) (2004) 409-426. ## [167] S.R. Van Tomme, G. Storm, W.E. Hennink, In situ gelling hydrogels for pharmaceutical and biomedical applications, International journal of pharmaceu-tics 355(1-2) (2008) 1-18. ## [168] N.E. Fedorovich, M.H. Oudshoorn, D. van Geemen, W.E. Hennink, J. Al-blas, W.J. Dhert, The effect of photopolymerization on stem cells embedded in hydrogels, Biomaterials 30(3) (2009) 344-353. ## [169] S.J. Bryant, C.R. Nuttelman, K.S. Anseth, Cytocompatibility of UV and vis-ible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro, Journal of Biomaterials Science, Polymer Edition 11(5) (2000) 439-457. ## [170] Y. Murakami, M. Yokoyama, T. Okano, H. Nishida, Y. Tomizawa, M. Endo, H. Kurosawa, A novel synthetic tissue‐adhesive hydrogel using a crosslinkable polymeric micelle, Journal of Biomedical Materials Research Part A 80(2) (2007) 421-427. ## [171] V.S. Ghorpade, Preparation of hydrogels based on natural polymers via chemical reaction and cross-linking, Hydrogels Based on Natural Polymers, El-sevier2020, pp. 91-118. ## [172] H. Kolb, M. G. Finn, KB Sharpless, Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew. Chem. Int. Ed 40 (2001) 2004-2021. ## [173] D.A. Ossipov, J. Hilborn, Poly (vinyl alcohol)-based hydrogels formed by “click chemistry”, Macromolecules 39(5) (2006) 1709-1718. ## [174] X.D. Xu, C.S. Chen, B. Lu, Z.C. Wang, S.X. Cheng, X.Z. Zhang, R.X. Zhuo, Modular synthesis of thermosensitive P (NIPAAm‐co‐HEMA)/β‐CD based hy-drogels via click chemistry, Macromolecular rapid communications 30(3) (2009) 157-164. ## [175] W. Sheng, T. Liu, S. Liu, Q. Wang, X. Li, N. Guang, Temperature and pH responsive hydrogels based on polyethylene glycol analogues and poly (methac-rylic acid) via click chemistry, Polymer International 64(10) (2015) 1415-1424. ## [176] B.G. De Geest, W. Van Camp, F.E. Du Prez, S.C. De Smedt, J. Demeester, W.E. Hennink, Biodegradable microcapsules designed via ‘click’chemistry, Chemical Communications (2) (2008) 190-192. ## [177] C.D. Hermann, D.S. Wilson, K.A. Lawrence, X. Ning, R. Olivares-Navar-rete, J.K. Williams, R.E. Guldberg, N. Murthy, Z. Schwartz, B.D. Boyan, Rapidly polymerizing injectable click hydrogel therapy to delay bone growth in a murine re-synostosis model, Biomaterials 35(36) (2014) 9698-9708. ## [178] M.N. Ganivada, P. Kumar, R. Shunmugam, A unique polymeric gel by thiol–alkyne click chemistry, RSC Advances 5(62) (2015) 50001-50004. ## [179] K.W. Boere, B.G. Soliman, D.T. Rijkers, W.E. Hennink, T. Vermonden, Thermoresponsive injectable hydrogels cross-linked by native chemical ligation, Macromolecules 47(7) (2014) 2430-2438. ## [180] S. Mukherjee, M.R. Hill, B.S. Sumerlin, Self-healing hydrogels containing reversible oxime crosslinks, Soft matter 11(30) (2015) 6152-6161. ## [181] M. Fan, Y. Ma, Z. Zhang, J. Mao, H. Tan, X. Hu, Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering, Materials Science and Engineering: C 56 (2015) 311-317. ## [182] D.E. Ciolacu, R. Nicu, F. Ciolacu, Cellulose-based hydrogels as sustained drug-delivery systems, Materials 13(22) (2020) 5270. ## [183] M.C. Koetting, J.T. Peters, S.D. Steichen, N.A. Peppas, Stimulus-responsive hydrogels: Theory, modern advances, and applications, Materials Science and En-gineering: R: Reports 93 (2015) 1-49. ## [184] Q. Chai, Y. Jiao, X. Yu, Hydrogels for biomedical applications: their charac-teristics and the mechanisms behind them, Gels 3(1) (2017) 6. ## [185] S. Choudhary, J.M. Reck, A.J. Carr, S.R. Bhatia, Hydrophobically modified alginate for extended release of pharmaceuticals, Polymers for Advanced Technol-ogies 29(1) (2018) 198-204. ## [186] M.P. Di Cagno, F. Clarelli, J. Våbenø, C. Lesley, S.D. Rahman, J. Cauz-zo, E. Franceschinis, N. Realdon, P.C. Stein, Experimental determination of drug diffusion coefficients in unstirred aqueous environments by temporally resolved concentration measurements, Molecular pharmaceutics 15(4) (2018) 1488-1494. ## [187] S. Kirchhof, M. Abrami, V. Messmann, N. Hammer, A.M. Goepferich, M. Grassi, F.P. Brandl, Diels–Alder hydrogels for controlled antibody release: correla-tion between mesh size and release rate, Molecular Pharmaceutics 12(9) (2015) 3358-3368. ## ## [188] Y. Wu, S. Joseph, N. Aluru, Effect of cross-linking on the diffusion of wa-ter, ions, and small molecules in hydrogels, The Journal of Physical Chemistry B 113(11) (2009) 3512-3520. ## [189] M. Bansal, A. Dravid, Z. Aqrawe, J. Montgomery, Z. Wu, D. Svirskis, Con-ducting polymer hydrogels for electrically responsive drug delivery, Journal of Controlled Release 328 (2020) 192-209. ## [190] M. Young, P. Carroad, R. Bell, Estimation of diffusion coefficients of pro-teins, Biotechnology and bioengineering 22(5) (1980) 947-955. ## [191] B.E. Jensen, K. Edlund, A.N. Zelikin, Micro-structured, spontaneously erod-ing hydrogels accelerate endothelialization through presentation of conjugated growth factors, Biomaterials 49 (2015) 113-124. ## [192] R. Chandrawati, Enzyme-responsive polymer hydrogels for therapeutic de-livery, Experimental Biology and Medicine 241(9) (2016) 972-979. ## [193] S.P. Zustiak, J.B. Leach, Characterization of protein release from hydrolyt-ically degradable poly (ethylene glycol) hydrogels, Biotechnology and bioengineering 108(1) (2011) 197-206. ## [194] S. Sheth, E. Barnard, B. Hyatt, M. Rathinam, S.P. Zustiak, Predicting Drug Release from Degradable Hydrogels Using Fluorescence Correlation Spectrosco-py and Mathematical Modeling, Frontiers in bioengineering and biotechnology (2019) 410. ## [195] M. Hamidi, A. Azadi, P. Rafiei, Hydrogel nanoparticles in drug delivery, Advanced drug delivery reviews 60(15) (2008) 1638-1649. ## [196] L. Zhang, G. Zhang, J. Lu, H. Liang, Preparation and characterization of car-boxymethyl cellulose/polyvinyl alcohol blend film as a potential coating material, Polymer-Plastics Technology and Engineering 52(2) (2013) 163-167. ## [197] X. Qiu, S. Tao, X. Ren, S. Hu, Modified cellulose films with controlled per-meatability and biodegradability by crosslinking with toluene diisocyanate under homogeneous conditions, Carbohydrate polymers 88(4) (2012) 1272-1280. ## [198] H. Huang, X. Qi, Y. Chen, Z. Wu, Thermo-sensitive hydrogels for delivering biotherapeutic molecules: A review, Saudi Pharmaceutical Journal 27(7) (2019) 990-999. ## [199] N. Kamaly, B. Yameen, J. Wu, O.C. Farokhzad, Degradable controlled-re-lease polymers and polymeric nanoparticles: mechanisms of controlling drug re-lease, Chemical reviews 116(4) (2016) 2602-2663. ## [200] S. Sim, A. Figueiras, F. Veiga, Modular hydrogels for drug delivery, (2012). ## [201] N. Das, Biodegradable hydrogels for controlled drug delivery, Mondal IM, editions. Cellulose-based superabsorbent hydrogels. Springer Nature (2018) 1-41. ## [202] Q. Jiang, N. Reddy, Y. Yang, Cytocompatible cross-linking of electrospun zein fibers for the development of water-stable tissue engineering scaffolds, Acta biomaterialia 6(10) (2010) 4042-4051. ## [203] T.M. O’Shea, A.A. Aimetti, E. Kim, V. Yesilyurt, R. Langer, Synthesis and characterization of a library of in‐situ curing, nonswelling ethoxylated polyol thi-ol‐ene hydrogels for tailorable macromolecule delivery, Advanced Materials 27(1) (2015) 65-72. ## [204] H.K. Lau, A. Paul, I. Sidhu, L. Li, C.R. Sabanayagam, S.H. Parekh, K.L. Kiick, Microstructured Elastomer‐PEG Hydrogels via Kinetic Capture of Aqueous Liquid–Liquid Phase Separation, Advanced Science 5(6) (2018) 1701010. ## [205] M.K. Nguyen, O. Jeon, M.D. Krebs, D. Schapira, E. Alsberg, Sustained lo-calized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation, Biomaterials 35(24) (2014) 6278-6286. ## [206] T. Saito, Y. Tabata, Preparation of gelatin hydrogels incorporating small in-terfering RNA for the controlled release, Journal of drug targeting 20(10) (2012) 864-872. ## [207] F.M. Carbinatto, A.D. de Castro, R.C. Evangelista, B.S. Cury, Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices, Asian Journal of Pharmaceutical Sciences 9(1) (2014) 27-34. ## [208] I. Gibas, H. Janik, Synthetic polymer hydrogels for biomedical applications, (2010). ## [209] S.V. Sawant, S.V. Sankpal, K.R. Jadhav, V.J. Kadam, Hydrogel as drug deliv-ery system, Research Journal of Pharmacy and Technology 5(5) (2012) 561-569. ## [210] H. Hezaveh, I.I. Muhamad, I. Noshadi, L. Shu Fen, N. Ngadi, Swelling behaviour and controlled drug release from cross-linked κ-carrageenan/NaCMC hydrogel by diffusion mechanism, Journal of microencapsulation 29(4) (2012) 368-379.