{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:55:37Z","timestamp":1791327337824,"version":"4.3.1"},"reference-count":54,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2023YFC2812004"],"award-info":[{"award-number":["2023YFC2812004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Brucellosis is a zoonotic infectious disease that has long endangered the development of animal husbandry and human health. Currently, vaccination stands as the most efficacious method for preventing and managing brucellosis. Alum, as the most commonly used adjuvant for the brucellosis vaccine, has obvious disadvantages, such as the formation of granulomas and its non-degradability. Therefore, the aims of this study were to prepare an absorbable, injectable, and biocompatible hydroxypropyl chitin (HPCT) thermosensitive hydrogel and to evaluate its immunization efficacy as an adjuvant for Brucella antigens. Specifically, etherification modification of marine natural polysaccharide chitin was carried out to obtain a hydroxypropyl chitin. Rheological studies demonstrated the reversible temperature sensitivity of HPCT hydrogel. Notably, 5 mg\/mL of bovine serum albumin can be loaded in HPCT hydrogels and released continuously for more than one week. Furthermore, the L929 cytotoxicity test and in vivo degradation test in rats proved that an HPCT hydrogel had good cytocompatibility and histocompatibility and can be degraded and absorbed in vivo. In mouse functional experiments, as adjuvants for Brucella antigens, an HPCT hydrogel showed better specific antibody expression levels and cytokine (Interleukin-4, Interferon-\u03b3) expression levels than alum. Thus, we believe that HPCT hydrogels hold much promise in the development of adjuvants.<\/jats:p>","DOI":"10.3390\/polym16192815","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T12:02:20Z","timestamp":1728043340000},"page":"2815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Thermosensitive and Degradable Chitin-Based Hydrogel as a Brucellosis Vaccine Adjuvant"],"prefix":"10.3390","volume":"16","author":[{"given":"Ruibao","family":"Ju","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Chi","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanshun","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoqin","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"ref_1","first-page":"21","article-title":"Brucellosis: Past, present and future","volume":"31","author":"Nicoletti","year":"2010","journal-title":"Prilozi"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117280","DOI":"10.1016\/j.jns.2020.117280","article-title":"Brucellosis","volume":"420","author":"Shakir","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2174\/1574891X11308010007","article-title":"Clinical presentations and diagnosis of brucellosis","volume":"8","author":"Metan","year":"2013","journal-title":"Recent. Pat. Antiinfect. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/j.ajpath.2015.03.003","article-title":"Pathogenesis and immunobiology of brucellosis: Review of Brucella-host interactions","volume":"185","author":"Ficht","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1136\/bmj.39497.500903.25","article-title":"Treatment of human brucellosis: Systematic review and meta-analysis of randomised controlled trials","volume":"336","author":"Skalsky","year":"2008","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1574-6976.2010.00211.x","article-title":"Towards a Brucella vaccine for humans","volume":"34","author":"Perkins","year":"2010","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Avila-Calder\u00f3n, E.D., Lopez-Merino, A., Sriranganathan, N., Boyle, S.M., and Contreras-Rodr\u00edguez, A. (2013). A History of the Development of Brucella Vaccines. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/743509"},{"key":"ref_8","unstructured":"(2005). Guideline on Adjuvants in Vaccines for Human Use, The European Medicines Agency."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","article-title":"Vaccine adjuvants: Putting innate immunity to work","volume":"33","author":"Coffman","year":"2010","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Thomas, S. (2022). Developments in Vaccine Adjuvants. Vaccine Design: Methods and Protocols, Volume 3. Resources for Vaccine Development, Springer.","DOI":"10.1007\/978-1-0716-1892-9"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2013.12.007","article-title":"Immunomodulatory properties of the vaccine adjuvant alum","volume":"28","author":"Oleszycka","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1099\/jmm.0.038943-0","article-title":"Alum adjuvant: Some of the tricks of the oldest adjuvant","volume":"61","author":"Kool","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/S0264-410X(02)00168-8","article-title":"The global impact of vaccines containing aluminium adjuvants","volume":"20","author":"Clements","year":"2002","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.actbio.2016.02.028","article-title":"Thermosensitive injectable in-situ forming carboxymethyl chitin hydrogel for three-dimensional cell culture","volume":"35","author":"Liu","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119879","DOI":"10.1016\/j.carbpol.2022.119879","article-title":"Chitosan hydrochloride salt stabilized emulsion as vaccine adjuvant","volume":"296","author":"Wang","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1002\/jbm.a.37240","article-title":"Chitosan and alginate salt as biomaterials are potential natural adjuvants for killed cholera vaccine","volume":"109","author":"AbdelAllah","year":"2021","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.ijbiomac.2021.05.155","article-title":"Chitosan, alginate, hyaluronic acid, gums, and \u03b2-glucan as potent adjuvants and vaccine delivery systems for viral threats including SARS-CoV-2: A review","volume":"182","author":"Mallakpour","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pellis, A., Guebitz, G.M., and Nyanhongo, G.S. (2022). Chitosan: Sources, Processing and Modification Techniques. Gels, 8.","DOI":"10.3390\/gels8070393"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/j.1348-0421.1984.tb00746.x","article-title":"Protecting effect of chitin and chitosan on experimentally induced murine candidiasis","volume":"28","author":"Suzuki","year":"1984","journal-title":"Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nishimura, K., Nishimura, S., Nishi, N., Tokura, S., Azuma, I., Nishimura, K., Nishimura, S., Nishi, N., Tokura, S., and Azuma, I. (1986). Immunological Activity of Chitin Derivatives. Chitin in Nature and Technology, Plenum Press.","DOI":"10.1007\/978-1-4613-2167-5_56"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.ijbiomac.2020.07.098","article-title":"Chitin and its derivatives: Structural properties and biomedical applications","volume":"164","author":"Ahmad","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"387023","DOI":"10.1155\/2013\/387023","article-title":"Chitin, chitosan, and glycated chitosan regulate immune responses: The novel adjuvants for cancer vaccine","volume":"2013","author":"Li","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_23","first-page":"1126","article-title":"Intranasal administration of immunogenic poly-epitope from influenza H1N1 and H3N2 viruses adjuvanted with chitin and chitosan microparticles in BALB\/c mice","volume":"24","author":"Sadeghi","year":"2021","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.2147\/IJN.S317113","article-title":"Chitosan Nanovaccines as Efficient Carrier Adjuvant System for IL-12 with Enhanced Protection Against HBV","volume":"16","author":"Zhao","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.2174\/0929867326666190227192527","article-title":"Quaternized Chitosan Nanoparticles in Vaccine Applications","volume":"27","author":"Yu","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.actbio.2020.03.039","article-title":"A moldable thermosensitive hydroxypropyl chitin hydrogel for 3D cartilage regeneration in vitro and in vivo","volume":"108","author":"Xu","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_27","first-page":"978","article-title":"Simultaneous determination of the degree of substitution and moisture content of hydroxypropyl chitosan by elemental analysis","volume":"33","author":"Zhang","year":"2014","journal-title":"Chin. J. Anal. Lab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"S\u00e6b\u00f8, I., Bj\u00f8r\u00e5s, M., Franzyk, H., Helgesen, E., and Booth, J. (2023). Optimization of the Hemolysis Assay for the Assessment of Cytotoxicity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032914"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.1128\/IAI.67.9.4960-4962.1999","article-title":"Outer Membrane Proteins Omp10, Omp16, and Omp19 of Brucella spp. Are Lipoproteins","volume":"67","author":"Tibor","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s12275-020-0144-y","article-title":"Omp16, a conserved peptidoglycan-associated lipoprotein, is involved in Brucella virulence in vitro","volume":"58","author":"Zhi","year":"2020","journal-title":"J. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pasquevich, K.A., Carabajal, M.V., Guaimas, F.F., Bruno, L., Roset, M.S., Coria, L.M., Rey Serrantes, D.A., Comerci, D.J., and Cassataro, J. (2019). Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host\u2019s Proteolytic Defense System. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01436"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s10875-021-01068-6","article-title":"Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-\u03b2","volume":"41","author":"Vinh","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.cyto.2015.01.038","article-title":"History of interleukin-4","volume":"75","author":"Paul","year":"2015","journal-title":"Cytokine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1016\/j.carres.2004.06.017","article-title":"Influence of alkali-freezing treatment on the solid state structure of chitin","volume":"339","author":"Feng","year":"2004","journal-title":"Carbohydr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1021\/bm0492172","article-title":"Characterization of Uniaxially Aligned Chitin Film by 2D FT-IR Spectroscopy","volume":"6","author":"Yamaguchi","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.carbpol.2018.03.031","article-title":"Thermosensitive and photocrosslinkable hydroxypropyl chitin-based hydrogels for biomedical applications","volume":"192","author":"Yuan","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"117950","DOI":"10.1016\/j.carbpol.2021.117950","article-title":"Simultaneous determination of molar degree of substitution and its distribution fraction, degree of acetylation in hydroxypropyl chitosan by 1H NMR spectroscopy","volume":"263","author":"Wang","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.carres.2005.05.009","article-title":"Preparation and antimicrobial activity of hydroxypropyl chitosan","volume":"340","author":"Peng","year":"2005","journal-title":"Carbohydr. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1021\/ma021079q","article-title":"Shell-Restricted Swelling and Core Compression in Poly(N-isopropylacrylamide) CoreShell Microgels","volume":"36","author":"Jones","year":"2003","journal-title":"Macromolecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1039\/C9TB02052G","article-title":"Thermoresponsive polymers and their biomedical application in tissue engineering\u2014A review","volume":"8","author":"Doberenz","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wu, Y., Wenger, A., Golzar, H., and Tang, X. (2020). 3D bioprinting of bicellular liver lobule-mimetic structures via microextrusion of cellulose nanocrystal-incorporated shear-thinning bioink. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-77146-3"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0300-483X(80)90110-9","article-title":"Cytotoxicity of drugs and diverse chemical agents to cell cultures","volume":"16","year":"1980","journal-title":"Toxicology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0142-9612(84)90061-9","article-title":"Systemic effects of biomaterials","volume":"5","author":"Blac","year":"1984","journal-title":"Biomaterials"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chun, H.J., Reis, R.L., Motta, A., and Khang, G. (2020). Biocompatibility of Materials for Biomedical Engineering. Biomimicked Biomaterials: Advances in Tissue Engineering and Regenerative Medicine, Springer.","DOI":"10.1007\/978-981-15-3262-7"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.actbio.2019.06.021","article-title":"The blood compatibility challenge. Part 1: Blood-contacting medical devices: The scope of the problem","volume":"94","author":"Jaffer","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.actbio.2019.06.019","article-title":"The blood compatibility challenge. Part 4: Surface modification for hemocompatible materials: Passive and active approaches to guide blood-material interactions","volume":"94","author":"Maitz","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_47","unstructured":"Hou, L., and Sun, X. (2024, October 02). Biological Evaluation of Medical Devices\u2014Part 5:Tests for In Vitro Cytotoxicity. Inspection and Quarantine of the People\u2019s Republic of China. Available online: https:\/\/kns.cnki.net\/kcms2\/article\/abstract?v=cF0fONyw0YJxIX1tlEtAQZwQyyc2s6iiKFwYtGtplV7GG0x7j_fN-cWHDu2wcdKTFvb9-NJ2bLG-Q9sYDkJtzEIwIxP3GqgOX5Qd5sAfFxDoxbCDU0LZbcuamssUuKvL5hk24dlbI5BbPFp9usA1JIOHrAyUi_OnPsBaN6AECIkU12xG4ExB1V72ojGAbAmn&uniplatform=NZKPT&language=CHS."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Raut, H.K., Das, R., Liu, Z., Liu, X., and Ramakrishna, S. (2020). Biocompatibility of Biomaterials for Tissue Regeneration or Replacement. Biotechnol. J., 15.","DOI":"10.1002\/biot.202000160"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mukhametova, L.I., Zherdev, D.O., Kuznetsov, A.N., Yudina, O.N., Tsvetkov, Y.E., Eremin, S.A., Krylov, V.B., and Nifantiev, N.E. (2024). Fluorescence-Polarization-Based Assaying of Lysozyme with Chitooligosaccharide Tracers. Biomolecules, 14.","DOI":"10.3390\/biom14020170"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0008-6215(96)00332-1","article-title":"In Vitro degradation rates of partially n-acetylated chitosans in human serum","volume":"299","author":"Myhr","year":"1997","journal-title":"Carbohydr. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0378-5173(00)00428-2","article-title":"Characterization of thermosensitive chitosan gels for the sustained delivery of drugs","volume":"203","author":"Chenite","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13704","DOI":"10.3390\/molecules171213704","article-title":"An electrostatically crosslinked chitosan hydrogel as a drug carrier","volume":"17","author":"Kim","year":"2012","journal-title":"Molecules"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/15583724.2010.537798","article-title":"Responsive Polymers in Biology and Technology","volume":"51","author":"Bajpai","year":"2011","journal-title":"Polym. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hnasko, R. (2015). Indirect ELISA. ELISA: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-2742-5"}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/19\/2815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:48Z","timestamp":1760112648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/19\/2815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":54,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["polym16192815"],"URL":"https:\/\/doi.org\/10.3390\/polym16192815","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]}}}