{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:07:08Z","timestamp":1788930428644,"version":"build-2803163510"},"reference-count":162,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Funct. Biomater.","JFB"],"abstract":"<jats:p>Hydrogels are hydrated three-dimensional polymeric networks with biomedical potential because they can encapsulate therapeutic agents and provide localised, sustained, or stimulus-responsive drug delivery. Their performance is determined by interacting variables, including polymer composition, synthesis route, crosslinking chemistry, drug loading, swelling, degradation, and the biological microenvironment. This multidimensional design space often makes hydrogel development slow and dependent on trial-and-error experimentation. This review examines the data-driven development of biomedical hydrogels for controlled drug delivery, focusing on clinical applications and emerging machine-learning approaches that support material selection, formulation design, synthesis optimisation, and release prediction. The review first discusses natural and synthetic hydrogels, including alginate, chitosan, gelatin-based systems, hyaluronic acid, and polyethylene glycol, with emphasis on how their physicochemical properties influence biocompatibility, synthesis flexibility, and drug-release behaviour. Key applications are then considered, including wound healing, cancer therapy, glucose-responsive insulin delivery, and inflammatory disease management. Particular attention is given to injectable and stimuli-responsive hydrogels, where formulation conditions and synthesis parameters can be tuned to improve localisation, therapeutic exposure, and release control. The review evaluates machine-learning methods, including random forest, gradient boosting, artificial neural networks, Gaussian process regression, and active learning, for predicting hydrogel properties, modelling release profiles, optimizing synthesis and formulation variables, and prioritizing experimental candidates. Finally, translational challenges are addressed, including small non-standardised datasets, limited external validation, weak in vitro-clinical correlations, material safety, explainability, reproducibility, scalability, and regulatory requirements. By integrating clinical, materials, synthesis, and machine-learning perspectives, this review highlights opportunities for developing safer and clinically relevant hydrogel-based drug-delivery systems.<\/jats:p>","DOI":"10.3390\/jfb17090444","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:35:29Z","timestamp":1788359729000},"page":"444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Data-Driven Development of Biomedical Hydrogels for Controlled Drug Delivery: Clinical Applications and Emerging Machine-Learning Approaches"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-2101","authenticated-orcid":false,"given":"Elham","family":"Eskandarnia","sequence":"first","affiliation":[{"name":"Faculty of Computer Studies, Arab Open University, Building 890, Street 3220, A\u2019ali 732, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4896-4210","authenticated-orcid":false,"given":"Ayah","family":"Binrajab","sequence":"additional","affiliation":[{"name":"Materials for Medicine Research Group, School of Medicine, Royal College of Surgeons in Ireland (RCSI), Medical University of Bahrain, Busaiteen 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3698-2421","authenticated-orcid":false,"given":"Adnan","family":"Alsaei","sequence":"additional","affiliation":[{"name":"Materials for Medicine Research Group, School of Medicine, Royal College of Surgeons in Ireland (RCSI), Medical University of Bahrain, Busaiteen 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0201-7791","authenticated-orcid":false,"given":"Fatema","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Materials for Medicine Research Group, School of Medicine, Royal College of Surgeons in Ireland (RCSI), Medical University of Bahrain, Busaiteen 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7648-9138","authenticated-orcid":false,"given":"Nasser","family":"Alahmed","sequence":"additional","affiliation":[{"name":"Materials for Medicine Research Group, School of Medicine, Royal College of Surgeons in Ireland (RCSI), Medical University of Bahrain, Busaiteen 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0175-0425","authenticated-orcid":false,"given":"Ahmad","family":"Zarwi","sequence":"additional","affiliation":[{"name":"Materials for Medicine Research Group, School of Medicine, Royal College of Surgeons in Ireland (RCSI), Medical University of Bahrain, Busaiteen 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Roshan","family":"Deen","sequence":"additional","affiliation":[{"name":"Materials for Medicine Research Group, School of Medicine, Royal College of Surgeons in Ireland (RCSI), Medical University of Bahrain, Busaiteen 228, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16071","DOI":"10.1038\/natrevmats.2016.71","article-title":"Designing hydrogels for controlled drug delivery","volume":"1","author":"Li","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vigata, M., Meinert, C., Hutmacher, D.W., and Bock, N. (2020). Hydrogels as drug delivery systems: A review of current characterization and evaluation techniques. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121188"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Raina, N., Pahwa, R., Bhattacharya, J., Paul, A.K., Nissapatorn, V., Pereira, M.L., Oliveira, S.M.R., Dolma, K.G., Rahmatullah, M., and Wilairatana, P. (2022). Drug delivery strategies and biomedical significance of hydrogels: Translational considerations. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030574"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Negut, I., and Bita, B. (2023). Exploring the potential of artificial intelligence for hydrogel development\u2014A short review. Gels, 9.","DOI":"10.3390\/gels9110845"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.tibtech.2022.09.019","article-title":"Towards machine learning for hydrogel drug delivery systems","volume":"41","author":"Owh","year":"2023","journal-title":"Trends Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"rbae109","DOI":"10.1093\/rb\/rbae109","article-title":"Integrating machine learning for the optimization of polyacrylamide\/alginate hydrogel","volume":"11","author":"Xu","year":"2024","journal-title":"Regen. Biomater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1038\/s41467-024-46866-9","article-title":"Developing a machine learning model for accurate nucleoside hydrogels prediction based on descriptors","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liu, B., and Chen, K. (2024). Advances in hydrogel-based drug delivery systems. Gels, 10.","DOI":"10.3390\/gels10040262"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bashir, S., Hina, M., Iqbal, J., Rajpar, A.H., Mujtaba, M.A., Alghamdi, N.A., Wageh, S., Ramesh, K., and Ramesh, S. (2020). Fundamental concepts of hydrogels: Synthesis, properties, and their applications. Polymers, 12.","DOI":"10.3390\/polym12112702"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1021\/acsabm.3c00984","article-title":"Alginate-chitosan biodegradable and biocompatible based hydrogel for breast cancer immunotherapy and diagnosis: A comprehensive review","volume":"7","author":"Patra","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bupphathong, S., Quiroz, C., Huang, W., Chung, P.F., Tao, H.Y., and Lin, C.H. (2022). Gelatin methacrylate hydrogel for tissue engineering applications-a review on material modifications. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020171"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1007\/s00266-025-05435-1","article-title":"Clinical durability of hyaluronic acid-based dermal fillers for facial application: A systematic review","volume":"50","author":"Andrade","year":"2026","journal-title":"Aesthetic Plast. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s44174-025-00303-7","article-title":"Pharmaceutical, biomedical, and biological implications of different grades of poloxamers","volume":"4","author":"Jena","year":"2026","journal-title":"Biomed. Mater. Devices"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2300105","DOI":"10.1002\/adhm.202300105","article-title":"Poly ethylene glycol (PEG)-based hydrogels for drug delivery in cancer therapy: A comprehensive review","volume":"12","author":"Wang","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Branco, A.C., Oliveira, A.S., Monteiro, I., Nolasco, P., Silva, D.C., Figueiredo-Pina, C.G., Cola\u00e7o, R., and Serro, A.P. (2022). PVA-based hydrogels loaded with diclofenac for cartilage replacement. Gels, 8.","DOI":"10.3390\/gels8030143"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1039\/C7CS00638A","article-title":"Hydrogels: Experimental characterization and mathematical modelling of their mechanical and diffusive behaviour","volume":"47","author":"Caccavo","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7090","DOI":"10.1038\/s41467-025-62540-0","article-title":"Peptide-based rigid nanorod-reinforced gelatin methacryloyl hydrogels for osteochondral regeneration and additive manufacturing","volume":"16","author":"Zhu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_18","first-page":"117","article-title":"Drug release from hydrogel matrices","volume":"17","author":"Zarzycki","year":"2010","journal-title":"Ecol. Chem. Eng. S"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40712-025-00283-y","article-title":"Stimuli-responsive hydrogels, their mass transfer, intermolecular interactions, and applications in biomedical devices","volume":"20","author":"Toews","year":"2025","journal-title":"J. Mater. Sci. Mater. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Protsak, I.S., and Morozov, Y.M. (2025). Fundamentals and advances in stimuli-responsive hydrogels and their applications: A review. Gels, 11.","DOI":"10.3390\/gels11010030"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lavrentev, F.V., Shilovskikh, V.V., Alabusheva, V.S., Yurova, V.Y., Nikitina, A.A., Ulasevich, S.A., and Skorb, E.V. (2023). Diffusion-limited processes in hydrogels with chosen applications from drug delivery to electronic components. Molecules, 28.","DOI":"10.3390\/molecules28155931"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1208\/s12249-024-02786-x","article-title":"A comprehensive review of hydrogel-based drug delivery systems: Classification, properties, recent trends, and applications","volume":"25","author":"Hameed","year":"2024","journal-title":"AAPS PharmSciTech"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1039\/D2TB02004A","article-title":"Solute diffusion and partitioning in multi-arm poly(ethylene glycol) hydrogels","volume":"11","author":"Richbourg","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1517\/17425241003602259","article-title":"Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems","volume":"7","author":"Fu","year":"2010","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Narayanaswamy, R., and Torchilin, V.P. (2019). Hydrogels and their applications in targeted drug delivery. Molecules, 24.","DOI":"10.3390\/molecules24030603"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ciolacu, D.E., Nicu, R., and Ciolacu, F. (2020). Cellulose-based hydrogels as sustained drug-delivery systems. Materials, 13.","DOI":"10.3390\/ma13225270"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1021\/acs.chemrev.5b00346","article-title":"Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release","volume":"116","author":"Kamaly","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ding, X., Yang, B., Ni, L., Niu, G., Si, X., Lu, N., and Hou, Z. (2025). Dual-crosslinked gelatin\/dextran medical hydrogels based on aldimine condensation and photopolymerization. Gels, 11.","DOI":"10.3390\/gels11110871"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1073\/pnas.1215498110","article-title":"Hydrogel drug delivery system with predictable and tunable drug release and degradation rates","volume":"110","author":"Ashley","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11385","DOI":"10.1021\/acs.chemrev.0c01177","article-title":"Translational applications of hydrogels","volume":"121","author":"Correa","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.addr.2018.03.007","article-title":"In situ forming injectable hydrogels for drug delivery and wound repair","volume":"127","author":"Dimatteo","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Parvin, N., Joo, S.W., and Mandal, T.K. (2025). Injectable biopolymer-based hydrogels: A next-generation platform for minimally invasive therapeutics. Gels, 11.","DOI":"10.3390\/gels11060383"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Alonso, J.M., Andrade Del Olmo, J., Perez Gonzalez, R., and Saez-Martinez, V. (2021). Injectable hydrogels: From laboratory to industrialization. Polymers, 13.","DOI":"10.3390\/polym13040650"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115973","DOI":"10.1016\/j.matdes.2026.115973","article-title":"Responsive to revolutionary: Thermoresponsive hydrogels pioneering drug delivery and tissue engineering","volume":"266","author":"Suvarna","year":"2026","journal-title":"Mater. Des."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lv, T., Chen, Y., Li, N., Liao, X., Heng, Y., Guo, Y., and Hu, K. (2025). A comprehensive review of thermosensitive hydrogels: Mechanism, optimization strategies, and applications. Gels, 11.","DOI":"10.3390\/gels11070544"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40824-018-0138-6","article-title":"Injectable hydrogels delivering therapeutic agents for disease treatment and tissue engineering","volume":"22","author":"Lee","year":"2018","journal-title":"Biomater. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lee, Y., Kim, M., Kim, N., Byun, S., Seo, S., and Han, J.Y. (2025). Injectable hydrogel systems for targeted drug delivery: From site-specific application to design strategy. Appl. Sci., 15.","DOI":"10.3390\/app152111599"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Almawash, S., Osman, S.K., Mustafa, G., and El Hamd, M.A. (2022). Current and future prospective of injectable hydrogels-design challenges and limitations. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030371"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Patroklou, G., Triantafyllopoulou, E., Goula, P.-E., Karali, V., Chountoulesi, M., Valsami, G., Pispas, S., and Pippa, N. (2025). PH-responsive hydrogels: Recent advances in pharmaceutical applications. Polymers, 17.","DOI":"10.3390\/polym17111451"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.2147\/IJN.S245743","article-title":"Healthcare applications of pH-sensitive hydrogel-based devices: A review","volume":"15","author":"Hendi","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, J., Yang, W., Li, Y., Ma, X., Xie, Y., Zhou, G., and Liu, S. (2024). Dual-temperature\/pH-sensitive hydrogels with excellent strength and toughness crosslinked using three crosslinking methods. Gels, 10.","DOI":"10.3390\/gels10070480"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xin, H. (2022). Double-network tough hydrogels: A brief review on achievements and challenges. Gels, 8.","DOI":"10.3390\/gels8040247"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1038\/nprot.2017.053","article-title":"Shear-thinning and self-healing hydrogels as injectable therapeutics and for 3D-printing","volume":"12","author":"Loebel","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.1021\/la2041746","article-title":"Injectable solid peptide hydrogel as a cell carrier: Effects of shear flow on hydrogels and cell payload","volume":"28","author":"Yan","year":"2012","journal-title":"Langmuir"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cirillo, G., Spizzirri, U.G., Curcio, M., Nicoletta, F.P., and Iemma, F. (2019). Injectable hydrogels for cancer therapy over the last decade. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11090486"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"122671","DOI":"10.1016\/j.ijpharm.2023.122671","article-title":"A review of conventional and emerging technologies for hydrogels sterilization","volume":"634","author":"Bento","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, Y., and Wu, B.M. (2023). Current advances in stimuli-responsive hydrogels as smart drug delivery carriers. Gels, 9.","DOI":"10.3390\/gels9100838"},{"key":"ref_48","first-page":"100186","article-title":"Smart\/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications","volume":"13","author":"Mady","year":"2021","journal-title":"Mater. Today Bio"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rizwan, M., Yahya, R., Hassan, A., Yar, M., Azzahari, A.D., Selvanathan, V., Sonsudin, F., and Abouloula, C.N. (2017). PH sensitive hydrogels in drug delivery: Brief history, properties, swelling, and release mechanism, material selection and applications. Polymers, 9.","DOI":"10.3390\/polym9040137"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mser.2015.04.001","article-title":"Stimulus-responsive hydrogels: Theory, modern advances, and applications","volume":"93","author":"Koetting","year":"2015","journal-title":"Mater. Sci. Eng. R Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Morariu, S. (2023). Advances in the design of phenylboronic acid-based glucose-sensitive hydrogels. Polymers, 15.","DOI":"10.3390\/polym15030582"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/acs.bioconjchem.2c00094","article-title":"Redox-responsive hydrogels for tunable and \u201con-demand\u201d release of biomacromolecules","volume":"33","author":"Aydin","year":"2022","journal-title":"Bioconjugate Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2105408","DOI":"10.1002\/advs.202105408","article-title":"An injectable dual-function hydrogel protects against myocardial ischemia\/reperfusion injury by modulating ROS\/NO disequilibrium","volume":"9","author":"Hao","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Jiang, M., and Wang, T. (2024). Reactive oxygen species (ROS)-responsive biomaterials for treating myocardial ischemia-reperfusion injury. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1469393"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ansari, M.J., Rajendran, R.R., Mohanto, S., Agarwal, U., Panda, K., Dhotre, K., Manne, R., Deepak, A., Zafar, A., and Yasir, M. (2022). Poly(N-isopropylacrylamide)-based hydrogels for biomedical applications: A review of the state-of-the-art. Gels, 8.","DOI":"10.3390\/gels8070454"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Xing, Y., Zeng, B., and Yang, W. (2022). Light responsive hydrogels for controlled drug delivery. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1075670"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cis.2015.10.003","article-title":"Near-infrared light activated delivery platform for cancer therapy","volume":"226","author":"Lin","year":"2015","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e1902004","DOI":"10.1002\/adma.201902004","article-title":"Glucose-responsive insulin and delivery systems: Innovation and translation","volume":"32","author":"Wang","year":"2020","journal-title":"Adv. Mater."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jconrel.2015.09.011","article-title":"On-demand drug delivery from local depots","volume":"219","author":"Brudno","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1080\/17425247.2022.2110582","article-title":"Localized, on-demand, sustained drug delivery from biopolymer-based materials","volume":"19","author":"Wu","year":"2022","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e2306152","DOI":"10.1002\/advs.202306152","article-title":"Stimulus-responsive hydrogels as drug delivery systems for inflammation targeted therapy","volume":"11","author":"Yu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.polymer.2008.01.027","article-title":"Hydrogels in drug delivery: Progress and challenges","volume":"49","author":"Hoare","year":"2008","journal-title":"Polymer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic foot ulcers: A review","volume":"330","author":"Armstrong","year":"2023","journal-title":"JAMA"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Burgess, J.L., Wyant, W.A., Abdo Abujamra, B., Kirsner, R.S., and Jozic, I. (2021). Diabetic wound-healing science. Medicina, 57.","DOI":"10.3390\/medicina57101072"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e3687","DOI":"10.1002\/dmrr.3687","article-title":"IWGDF\/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF\/IDSA 2023)","volume":"40","author":"Senneville","year":"2024","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1039\/D4BM00349G","article-title":"A novel chitosan-PEG hydrogel embedded with in situ silver nanoparticles of Clerodendrum glandulosum Lindl. extract: Evaluation of its in vivo diabetic wound healing properties using an image-guided machine learning model","volume":"12","author":"Majie","year":"2024","journal-title":"Biomater. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e2414989","DOI":"10.1002\/adma.202414989","article-title":"Skin-inspired and self-regulated hydrophobic hydrogel for diabetic wound therapy","volume":"37","author":"Liu","year":"2025","journal-title":"Adv. Mater."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"129725","DOI":"10.1016\/j.ijbiomac.2024.129725","article-title":"Engineered keratin\/bFGF hydrogel to promote diabetic wound healing in rats","volume":"261","author":"Sun","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"0066","DOI":"10.34133\/bmr.0066","article-title":"Diphasic CeO2 nanocrystal\/bioactive glass nanosphere-based composite hydrogel for diabetic wound healing by reactive oxygen species scavenging and inflammation regulation","volume":"28","author":"Qin","year":"2024","journal-title":"Biomater. Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Alsaei, A., Zarwi, A., Binrajab, A., Rahimi, F., AlAnsari, R., Kumar, M.P., Butler, A.E., Atkin, S.L., and Deen, G.R. (2026). Alginate-based biomaterials: From fundamental \u201cegg-box\u201d chemistry to diverse biomedical and metabolic management of obesity and diabetes. Gels, 12.","DOI":"10.3390\/gels12030250"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4103\/2321-3868.143616","article-title":"Polymeric hydrogels for burn wound care: Advanced skin wound dressings and regenerative templates","volume":"2","author":"Madaghiele","year":"2014","journal-title":"Burn. Trauma."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e2404255","DOI":"10.1002\/adhm.202404255","article-title":"Hyaluronic acid-based self-healing hydrogels for diabetic wound healing","volume":"14","author":"Chhillar","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1464-5491.2007.02079.x","article-title":"Silver Dressing Study Group. Prospective randomized controlled study of Hydrofiber\u00ae dressing containing ionic silver or calcium alginate dressings in non-ischaemic diabetic foot ulcers","volume":"24","author":"Jude","year":"2007","journal-title":"Diabet. Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"He, X., Wei, Y., and Xu, K. (2025). Hydrogel-based treatment of diabetic wounds: From smart responsive to smart monitoring. Gels, 11.","DOI":"10.3390\/gels11080647"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00262-021-03013-3","article-title":"Chemotherapy: A double-edged sword in cancer treatment","volume":"71","author":"Behranvand","year":"2022","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jconrel.2024.01.072","article-title":"Locoregional drug delivery for cancer therapy: Preclinical progress and clinical translation","volume":"367","author":"Shaha","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"119182","DOI":"10.1016\/j.biomaterials.2019.04.027","article-title":"Advances in drug delivery for post-surgical cancer treatment","volume":"219","author":"Bu","year":"2019","journal-title":"Biomaterials"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101308","DOI":"10.1016\/j.mtbio.2024.101308","article-title":"Hydrogel local drug delivery systems for postsurgical management of tumors: Status quo and perspectives","volume":"29","author":"Zhong","year":"2024","journal-title":"Mater. Today Bio"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"139137","DOI":"10.1016\/j.ijbiomac.2024.139137","article-title":"Natural polysaccharide hydrogel delivery system remodeling tumor microenvironment to promote postoperative tumor therapy","volume":"291","author":"Liu","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2400476","DOI":"10.1080\/10717544.2024.2400476","article-title":"Recent advances of injectable in situ-forming hydrogels for preventing postoperative tumor recurrence","volume":"31","author":"Wang","year":"2024","journal-title":"Drug Deliv."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pbiomolbio.2025.12.002","article-title":"Injectable hydrogel: A promising frontier in cancer therapy","volume":"199","author":"Farajollahi","year":"2026","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Fan, D.Y., Tian, Y., and Liu, Z.J. (2019). Injectable hydrogels for localized cancer therapy. Front. Chem., 7.","DOI":"10.3389\/fchem.2019.00675"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1007\/s13346-025-01967-w","article-title":"Application and development prospects of bio-based smart responsive hydrogels in insulin delivery","volume":"15","author":"Su","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/acsmaterialsau.4c00138","article-title":"Glucose-responsive materials for smart insulin delivery: From protein-based to protein-free design","volume":"5","author":"Pal","year":"2025","journal-title":"ACS Mater. Au"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Li, L., and Wang, Y. (2025). Advancements in injectable hydrogels for controlled insulin delivery: A comprehensive review of the design, properties and therapeutic applications for diabetes and its complications. Polymers, 17.","DOI":"10.3390\/polym17060780"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"eaaq0723","DOI":"10.1126\/sciadv.aaq0723","article-title":"Synthetic \u201csmart gel\u201d provides glucose-responsive insulin delivery in diabetic mice","volume":"3","author":"Matsumoto","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6758","DOI":"10.1021\/nn401617u","article-title":"Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery","volume":"7","author":"Gu","year":"2013","journal-title":"ACS Nano"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/cpt.1215","article-title":"Clinical evaluation of MK-2640: An insulin analog with glucose-responsive properties","volume":"105","author":"Krug","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e508","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: A systematic analysis for the Global Burden of Disease Study 2021","volume":"5","author":"Steinmetz","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1016\/S2665-9913(23)00211-4","article-title":"Global, regional, and national burden of rheumatoid arthritis, 1990\u20132020, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021","volume":"5","author":"Black","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e2303794","DOI":"10.1002\/adhm.202303794","article-title":"Intra-articular injectable biomaterials for cartilage repair and regeneration","volume":"13","author":"Kalairaj","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e12060","DOI":"10.1002\/jeo2.12060","article-title":"Intra-articular corticosteroids for the treatment of osteoarthritis: A systematic review and meta-analysis on the comparison of different molecules and doses","volume":"11","author":"Bensa","year":"2024","journal-title":"J. Exp. Orthop."},{"key":"ref_93","first-page":"1","article-title":"Application of injectable hydrogels as delivery systems in osteoarthritis and rheumatoid arthritis","volume":"85","author":"Zhu","year":"2024","journal-title":"Br. J. Hosp. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.21037\/atm-21-684","article-title":"Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief","volume":"9","author":"Wang","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sarsenova, M., Raimagambetov, Y., Issabekova, A., Karzhauov, M., Kudaibergen, G., Akhmetkarimova, Z., Batpen, A., Ramankulov, Y., and Ogay, V. (2022). Regeneration of osteochondral defects by combined delivery of synovium-derived mesenchymal stem cells, TGF-\u03b21 and BMP-4 in heparin-conjugated fibrin hydrogel. Polymers, 14.","DOI":"10.3390\/polym14245343"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e069722","DOI":"10.1136\/bmj-2022-069722","article-title":"Viscosupplementation for knee osteoarthritis: Systematic review and meta-analysis","volume":"378","author":"Pereira","year":"2022","journal-title":"BMJ"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Park, J.G., Sim, J., and Han, S.B. (2024). Association between intra-articular hyaluronic acid injections in delaying total knee arthroplasty and safety evaluation in primary knee osteoarthritis: Analysis based on Health Insurance Review and Assessment Service (HIRA) claim database in Republic of Korea. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-07698-2"},{"key":"ref_98","first-page":"14","article-title":"Injectable polymeric nanoparticle hydrogel system for long-term anti-inflammatory effect to treat osteoarthritis","volume":"7","author":"Seo","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Browne, D., Briggs, F., and Asuri, P. (2023). Role of polymer concentration on the release rates of proteins from single- and double-network hydrogels. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316970"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"101014","DOI":"10.1016\/j.mtbio.2024.101014","article-title":"AI energized hydrogel design, optimization and application in biomedicine","volume":"25","author":"Li","year":"2024","journal-title":"Mater. Today Bio"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Fareed, M.M., and Shityakov, S. (2025). Next-generation hydrogel design: Computational advances in synthesis, characterization, and biomedical applications. Polymers, 17.","DOI":"10.3390\/polym17101373"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.apm.2022.08.008","article-title":"Optimal loading of hydrogel-based drug-delivery systems","volume":"112","author":"Penn","year":"2022","journal-title":"Appl. Math. Model."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Zhao, L., Zhou, Y., Zhang, J., Liang, H., Chen, X., and Tan, H. (2023). Natural Polymer-based hydrogels: From polymer to biomedical applications. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102514"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s43586-022-00179-7","article-title":"Engineered hydrogels for mechanobiology","volume":"2","author":"Blache","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Nguyen, H.T., Truong, B.C., and Dang, X.C. (2023). Polymer-based hydrogels applied in drug delivery: An overview. Gels, 9.","DOI":"10.3390\/gels9070523"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Hanykova, L., Stastna, J., and Krakovsky, I. (2024). Responsive acrylamide-based hydrogels: Advances in interpenetrating polymer structures. Gels, 10.","DOI":"10.3390\/gels10070414"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Ho, T.C., Chang, C.C., Chan, H.P., Chung, T.W., Shu, C.W., Chuang, K.P., Duh, T.H., Yang, M.H., and Tyan, Y.C. (2022). Hydrogels: Properties and applications in biomedicine. Molecules, 27.","DOI":"10.3390\/molecules27092902"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Harmsen, R.A.G., Tuveng, T.R., Antonsen, S.G., Eijsink, V.G.H., and S\u00f8rlie, M. (2019). Can we make chitosan by enzymatic deacetylation of chitin?. Molecules, 24.","DOI":"10.3390\/molecules24213862"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"39844","DOI":"10.1039\/C5RA05734E","article-title":"Recent advances in crosslinking chemistry of biomimetic poly(ethylene glycol) hydrogels","volume":"5","author":"Lin","year":"2015","journal-title":"RSC Adv."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.actbio.2013.08.029","article-title":"Effects of crosslinking on the mechanical properties, drug release, and cytocompatibility of protein polymers","volume":"10","author":"Martinez","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1049\/bsb2.12050","article-title":"Recent developments in stimuli-responsive hydrogels for biomedical applications","volume":"8","author":"Liu","year":"2022","journal-title":"Biosurface Biotribol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Duceac, I.A., and Coseri, S. (2022). Chitosan Schiff-base hydrogels-a critical perspective review. Gels, 8.","DOI":"10.3390\/gels8120779"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Kim, M.K., Lee, J., and Kang, A.R. (2026). Stimuli-responsive hydrogels: From swelling\u2013deswelling mechanisms to biomedical applications. Nanomaterials, 16.","DOI":"10.3390\/nano16050329"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Itkor, P., and Lee, Y.S. (2023). State-of-the-art insights and potential applications of cellulose-based hydrogels in food packaging: Advances towards sustainable trends. Gels, 9.","DOI":"10.3390\/gels9060433"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7335","DOI":"10.1039\/C3CS60040H","article-title":"Designing degradable hydrogels for orthogonal control of cell microenvironments","volume":"42","author":"Kharkar","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Naomi, R., Bahari, H., Ridzuan, P.M., and Othman, F. (2021). Natural-based biomaterial for skin wound healing (gelatin vs. collagen): Expert review. Polymers, 13.","DOI":"10.3390\/polym13142319"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"13781","DOI":"10.1039\/D5TB01524C","article-title":"Hydrolytic degradation of PEG-based thiol-norbornene hydrogels enables multi-modal controlled release","volume":"13","author":"Dimmitt","year":"2025","journal-title":"J. Mater. Chem. B"},{"key":"ref_118","first-page":"467","article-title":"Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema","volume":"8","author":"Fong","year":"2013","journal-title":"Clin. Interv. Aging"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1002\/pol.20220154","article-title":"Progress in the mechanical enhancement of hydrogels: Fabrication strategies and underlying mechanisms","volume":"60","author":"Lin","year":"2022","journal-title":"J. Polym. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Roca-Arroyo, A.F., Gutierrez-Rivera, J.A., Morton, L.D., and Castilla-Casadiego, D.A. (2025). Hydrogel network architecture design space: Impact on mechanical and viscoelastic properties. Gels, 11.","DOI":"10.3390\/gels11080588"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1021\/acsmacrolett.9b00276","article-title":"Modern strategies to achieve tissue-mimetic, mechanically robust hydrogels","volume":"8","author":"Means","year":"2019","journal-title":"ACS Macro Lett."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.1016\/j.biomaterials.2010.03.064","article-title":"Cell-laden microengineered gelatin methacrylate hydrogels","volume":"31","author":"Nichol","year":"2010","journal-title":"Biomaterials"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Sun, M., Sun, X., Wang, Z., Guo, S., Yu, G., and Yang, H. (2018). Synthesis and properties of gelatin methacryloyl (gelma) hydrogels and their recent applications in load-bearing tissue. Polymers, 10.","DOI":"10.3390\/polym10111290"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Mohseni-Motlagh, S.F., Dolatabadi, R., Baniassadi, M., and Baghani, M. (2023). Application of the quality by design concept (qbd) in the development of hydrogel-based drug delivery systems. Polymers, 15.","DOI":"10.3390\/polym15224407"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.biomaterials.2015.08.045","article-title":"Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels","volume":"73","author":"Yue","year":"2015","journal-title":"Biomaterials"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"115171","DOI":"10.1016\/j.jconrel.2026.115171","article-title":"Fast-tracking complex formulation development with multi-objective Bayesian optimisation","volume":"397","author":"Liu","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101335","DOI":"10.1016\/j.nexres.2026.101335","article-title":"Artificial intelligence & machine learning in hydrogel: Revolutionizing design and optimization\u2014Detailed review","volume":"5","author":"Aboti","year":"2026","journal-title":"Next Res."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Briggs, F., Browne, D., and Asuri, P. (2022). Role of polymer concentration and crosslinking density on release rates of small molecule drugs. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084118"},{"key":"ref_129","first-page":"100083","article-title":"From fabrication to function: Mechanical insights into GelMA microneedle arrays","volume":"3","author":"Zargar","year":"2025","journal-title":"Smart Mater. Manuf."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"116088","DOI":"10.1016\/j.matdes.2026.116088","article-title":"Machine learning\u2013enabled intelligent hydrogels: Applications and future perspectives","volume":"266","author":"Zhang","year":"2026","journal-title":"Mater. Des."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"14967","DOI":"10.1039\/D5TB01944C","article-title":"Artificial intelligence-enabled hydrogels: Innovations and applications","volume":"13","author":"Zhang","year":"2025","journal-title":"J. Mater. Chem. B"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s42979-022-01161-6","article-title":"Deep learning techniques for smart meter data analytics: A review","volume":"3","author":"Eskandarnia","year":"2022","journal-title":"SN Comput Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"103618","DOI":"10.1016\/j.scs.2021.103618","article-title":"An embedded deep-clustering-based load profiling framework","volume":"78","author":"Eskandarnia","year":"2021","journal-title":"Sustain. Cities Soc."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"851","DOI":"10.12785\/ijcds\/110170","article-title":"A taxonomy of smart meter analytics: Forecasting, knowledge discovery, and power management","volume":"11","author":"Eskandarnia","year":"2022","journal-title":"Int. J. Comput Digit Syst."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41586-025-09269-4","article-title":"Data-driven de novo design of super-adhesive hydrogels","volume":"644","author":"Liao","year":"2025","journal-title":"Nature"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"214323","DOI":"10.1016\/j.bioadv.2025.214323","article-title":"Artificial intelligence tool for prediction of ECM mimics hydrogel formulations via click chemistry","volume":"175","author":"Cadamuro","year":"2025","journal-title":"Biomater. Adv."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2300553","DOI":"10.1002\/smtd.202300553","article-title":"High-throughput synthesis and machine learning assisted design of photodegradable hydrogels","volume":"7","author":"Seifermann","year":"2023","journal-title":"Small Methods"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"44796","DOI":"10.1021\/acsami.3c12207","article-title":"Optimization of gelatin methacryloyl hydrogel properties through an artificial neural network model","volume":"15","author":"Karaoglu","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"102559","DOI":"10.1016\/j.nantod.2024.102559","article-title":"Smart hydrogel dressing for machine learning-enabled visual monitoring and promote diabetic wound healing","volume":"60","author":"Deng","year":"2025","journal-title":"Nano Today"},{"key":"ref_140","first-page":"121","article-title":"Interpretable machine learning-driven optimization of physicochemical properties in hydrogel scaffolds to promote macrophage polarization","volume":"7","author":"Han","year":"2026","journal-title":"Biomater. Transl."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Mohammad, S., Akand, R., Cook, K.M., Nilufar, S., and Chowdhury, F. (2024). Leveraging deep learning and generative AI for predicting rheological properties and material compositions of 3D printed polyacrylamide hydrogels. Gels, 10.","DOI":"10.3390\/gels10100660"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Xu, L., Liu, S., Lin, A., Su, Z., and Liang, D. (2025). Interpretable prediction and analysis of PVA hydrogel mechanical behavior using machine learning. Gels, 11.","DOI":"10.3390\/gels11070550"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e2409835","DOI":"10.1002\/advs.202409835","article-title":"Improved efficacy of triple-negative breast cancer immunotherapy via hydrogel-based co-delivery of CAR-T cells and mitophagy agonist","volume":"12","author":"Li","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"114602","DOI":"10.1016\/j.jconrel.2026.114602","article-title":"Automated active learning to optimize hydrogel drug release profiles","volume":"391","author":"Cheong","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41368-026-00438-3","article-title":"Machine learning-driven discovery of therapeutic nucleoside hydrogels for periodontitis","volume":"18","author":"Li","year":"2026","journal-title":"Int. J. Oral Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e2413695","DOI":"10.1002\/adma.202413695","article-title":"Machine Learning in Polymer Research","volume":"37","author":"Ge","year":"2025","journal-title":"Adv. Mater."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Song, Y., Bashyal, S., Cho, H.J., Woo, M.R., Kim, J.O., and Hwang, D. (2026). Interpretable two-stage machine learning for early and full drug release prediction in PLGA microspheres. Pharmaceuticals, 19.","DOI":"10.3390\/ph19050767"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"160018","DOI":"10.1038\/sdata.2016.18","article-title":"The FAIR guiding principles for scientific data management and stewardship","volume":"3","author":"Wilkinson","year":"2016","journal-title":"Sci. Data"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41587-019-0080-8","article-title":"FAIRsharing as a community approach to standards, repositories and policies","volume":"37","author":"Sansone","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/s41592-021-01205-4","article-title":"DOME: Recommendations for supervised machine learning validation in biology","volume":"18","author":"Walsh","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Vabalas, A., Gowen, E., Poliakoff, E., and Casson, A.J. (2019). Machine learning algorithm validation with a limited sample size. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224365"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"100804","DOI":"10.1016\/j.patter.2023.100804","article-title":"Leakage and the reproducibility crisis in machine-learning-based science","volume":"4","author":"Kapoor","year":"2023","journal-title":"Patterns"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Tao, Z.Z., Du, R., Huo, R., and Zheng, X. (2025). Artificial intelligence informed hydrogel biomaterials in additive manufacturing. Gels, 11.","DOI":"10.3390\/gels11120981"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1007\/s13346-025-02033-1","article-title":"Clinical translation of injectable hydrogels: From bioactive polymers to long-acting drug delivery systems","volume":"16","author":"Alonso","year":"2026","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41392-021-00830-x","article-title":"Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity","volume":"6","author":"Cao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"e10158","DOI":"10.1002\/btm2.10158","article-title":"Hydrogels in the clinic","volume":"5","author":"Mandal","year":"2020","journal-title":"Bioeng. Transl. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e10680","DOI":"10.1002\/btm2.10680","article-title":"Hydrogels in the clinic: An update","volume":"9","author":"Clegg","year":"2024","journal-title":"Bioeng. Transl. Med."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Varma, S., and Simon, R. (2006). Bias in error estimation when using cross-validation for model selection. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-91"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Kelly, C.J., Karthikesalingam, A., Suleyman, M., Corrado, G., and King, D. (2019). Key challenges for delivering clinical impact with artificial intelligence. BMC Med., 17.","DOI":"10.1186\/s12916-019-1426-2"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1039\/D5TB02265G","article-title":"Hydrogels for in vivo biomedical applications: Recent advances and future perspectives","volume":"14","author":"Shen","year":"2026","journal-title":"J. Mater. Chem. B"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1208\/s12249-024-02731-y","article-title":"Insights into translational and biomedical applications of hydrogels as versatile drug delivery systems","volume":"25","author":"Kohar","year":"2024","journal-title":"AAPS PharmSciTech"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41392-024-01852-x","article-title":"Harnessing the potential of hydrogels for advanced therapeutic applications: Current achievements and future directions","volume":"9","author":"Lu","year":"2024","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/17\/9\/444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:14:59Z","timestamp":1788927299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/17\/9\/444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":162,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jfb17090444"],"URL":"https:\/\/doi.org\/10.3390\/jfb17090444","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}