水凝胶在生物医学领域的研究进展

doi:10.13591/j.cnki.kqyx.2022.09.012

摘要/Abstract

摘要： 水凝胶是在水溶液中通过化学和/或物理交联而形成的三维网络聚合物。水凝胶常具有高吸水性和保水性,它高度水合的性质与细胞外基质类似,这赋予了水凝胶极好的生物相容性;除此之外,许多水凝胶还具有抗炎、抗氧化、抗癌等生物功能,因此水凝胶具有应用于生物医学领域的巨大潜力。目前,水凝胶在组织工程支架、药物载体以及生物医学装置中都发挥着重要作用。该文介绍了水凝胶的基本性质及在生物医学领域中常用的水凝胶,重点综述水凝胶在生物医学领域中的应用,并总结水凝胶应用的现状及在进一步临床转换过程中需要克服的一些问题。

关键词: 水凝胶, 组织工程, 药物载体

Abstract: Hydrogel is a three-dimensional network polymer formed by chemical and/or physical crosslinking in aqueous solution. Hydrogels often have high water absorption and water retention, and their highly hydrated properties are similar to those of extracellular matrix, which endows hydrogels with excellent biocompatibility. In addition, many hydrogels have biological functions such as anti-inflammatory, anti-oxidation and anti-cancer, so hydrogels have great potential for application in biomedicine. At present, hydrogels play an important role in tissue engineering scaffolds, drug carriers and biomedical devices. In this paper, basic properties of hydrogels and hydrogels commonly used in biomedicine are introduced, and the application of hydrogels in biomedicine is emphasized. Present situation of its application is summarized, and problems to be overcome in further clinical transformation of hydrogels are discussed.

Key words: hydrogels, tissue engineering, drug carriers

中图分类号:

R783.1

吴维, 吴迪, 马珊珊, 汤春波. 水凝胶在生物医学领域的研究进展[J]. 口腔医学, 2022, 42(9): 831-837.

WU Wei, WU Di, MA Shanshan, TANG Chunbo. Research progress of hydrogels in biomedicine[J]. Stomatology, 2022, 42(9): 831-837.

参考文献

[1] Buwalda SJ, Boere KW, Dijkstra PJ, et al. Hydrogels in a historical perspective: From simple networks to smart materials[J]. J Control Release, 2014, 190: 254-273.
[2] Kopeček J. Hydrogels from soft contact lenses and implants to self-assembled nanomaterials[J]. J Polym Sci A Polym Chem, 2009, 47(22):5929-5946.
[3] Shim WS, Yoo JS, Bae, et al. Novel injectable pH and temperature sensitive block copolymer hydrogel[J]. Biomacromolecules, 2005, 6(6):2930-2934.
[4] Kasiński A, Zielińska-Pisklak M, Kowalczyk S, et al. Synthesis and characterization of new biodegradable injectable thermosensitive smart hydrogels for 5-fluorouracil delivery[J]. Int J Mol Sci, 2021, 22(15):8330.
[5] Hennessy BT, Smith DL, Ram PT, et al. Exploiting the PI3K/AKT pathway for cancer drug discovery[J]. Nat Rev Drug Discov, 2005, 4(12):988-1004.
[6] Shi JB, Wang GB, Chen HL, et al. Schiff based injectable hydrogel for in situ pH-triggered delivery of doxorubicin for breast tumor treatment[J]. Polym Chem, 2014, 5(21):6180-6189.
[7] Qi XL, Wei W, Li JJ, et al. Salecan-based pH-sensitive hydrogels for insulin delivery[J]. Mol Pharm, 2017, 14(2):431-440.
[8] Fourniols T, Randolph LD, Staub A, et al. Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma[J]. J Control Release, 2015, 210: 95-104.
[9] Mandal A, Clegg JR, Anselmo AC, et al. Hydrogels in the clinic[J]. Bioeng Transl Med, 2020, 5(2):e10158.
[10] Liu XJ, Chen Y, Huang QL, et al. A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate[J]. Carbohydr Polym, 2014, 110: 62-69.
[11] Younes I, Rinaudo M. Chitin and chitosan preparation from marine sources. Structure, properties and applications[J]. Mar Drugs, 2015, 13(3):1133-1174.
[12] 孔杰, 李国强, 叶菁芸, 等. 纳米银/壳聚糖复合水凝胶的原位制备、表征及抗菌性能研究[J]. 功能材料, 2012, 43(12):1662-1664.
[13] Anitha A, Sowmya S, Kumar PTS, et al. Chitin and chitosan in selected biomedical applications[J]. Prog Polym Sci, 2014, 39(9):1644-1667.
[14] Chenite A, Buschmann M, Wang D, et al. Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions[J]. Carbohydr Polym, 2001, 46(1):39-47.
[15] Saravanan S, Vimalraj S, Thanikaivelan P, et al. A review on injectable chitosan/beta glycerophosphate hydrogels for bone tissue regeneration[J]. Int J Biol Macromol, 2019, 121: 38-54.
[16] Motamedian SR, Hosseinpour S, Ahsaie MG, et al. Smart scaffolds in bone tissue engineering: A systematic review of literature[J]. World J Stem Cells, 2015, 7(3):657-668.
[17] Xu JK, Strandman S, Zhu JX, et al. Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery[J]. Biomaterials, 2015, 37: 395-404.
[18] Kołodziejska M, Jankowska K, Klak M, et al. Chitosan as an underrated polymer in modern tissue engineering[J]. Nanomaterials (Basel), 2021, 11(11):3019.
[19] Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications[J]. Adv Mater, 2011, 23(12):H41-H56.
[20] Mayol L, De Stefano D, De Falco F, et al. Effect of hyaluronic acid on the thermogelation and biocompatibility of its blends with methyl cellulose[J]. Carbohydr Polym, 2014, 112: 480-485.
[21] Collins MN, Birkinshaw C. Morphology of crosslinked hyaluronic acid porous hydrogels[J]. J Appl Polym Sci, 2011, 120(2):1040-1049.
[22] Illgen RL Ⅱ, Forsythe TM Ⅱ, Pike JW Ⅱ, et al. Highly crosslinked vs conventional polyethylene particles—an in vitro comparison of biologic activities[J]. J Arthroplast, 2008, 23(5):721-731.
[23] Chircov C, Grumezescu AM, Bejenaru LE. Hyaluronic acid-based scaffolds for tissue engineering[J].Revue Roumaine De Morphol et Embryol, 2018, 59(1):71-76.
[24] He Y, Zhao WW, Dong ZX, et al. A biodegradable antibacterial alginate/carboxymethyl chitosan/Kangfuxin sponges for promoting blood coagulation and full-thickness wound healing[J]. Int J Biol Macromol, 2021, 167: 182-192.
[25] Hao YP, Zheng WP, Sun ZY, et al. Marine polysaccharide-based composite hydrogels containing fucoidan: Preparation, physicochemical characterization, and biocompatible evaluation[J]. Int J Biol Macromol, 2021, 183: 1978-1986.
[26] Dhingra K, Dinda AK, Kottarath SK, et al. Mucoadhesive silver nanoparticle-based local drug delivery system for peri-implantitis management in COVID-19 era. Part 1: Antimicrobial and safety in-vitro analysis[J]. J Oral Biol Craniofac Res, 2022, 12(1):177-181.
[27] Fu YP, Ding Y, Zhang LT, et al. Poly ethylene glycol (PEG)-Related controllable and sustainable antidiabetic drug delivery systems[J]. Eur J Med Chem, 2021, 217: 113372.
[28] Chow A, Stuckey DJ, Kidher E, et al. Human induced pluripotent stem cell-derived cardiomyocyte encapsulating bioactive hydrogels improve rat heart function post myocardial infarction[J]. Stem Cell Reports, 2017, 9(5):1415-1422.
[29] Rana MM, De la Hoz Siegler H. Tuning the properties of PNIPAm-based hydrogel scaffolds for cartilage tissue engineering[J]. Polymers (Basel), 2021, 13(18):3154.
[30] Xia Y, Zhu K, Lai H, et al. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation[J]. Exp Biol Med (Maywood), 2015, 240(5):593-600.
[31] Xu XM, Liu Y, Fu WB, et al. Poly(N-isopropylacrylamide)-based thermoresponsive composite hydrogels for biomedical applications[J]. Polymers (Basel), 2020, 12(3):E580.
[32] Langer R. Tissue engineering: A new field and its challenges[J]. Pharm Res, 1997, 14(7):840-841.
[33] Caballero Aguilar LM, Silva SM, Moulton SE. Growth factor delivery: Defining the next generation platforms for tissue engineering[J]. J Control Release, 2019, 306: 40-58.
[34] 陈有荣, 颜昕, 叶景, 等. 不同水凝胶支架材料用于软骨损伤修复研究进展[J]. 中国运动医学杂志, 2021, 40(5):385-392.
[35] Markstedt K, Mantas A, Tournier I, et al. 3D bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications[J]. Biomacromolecules, 2015, 16(5):1489-1496.
[36] Pan YS, Zhao Y, Kuang R, et al. Injectable hydrogel-loaded nano-hydroxyapatite that improves bone regeneration and alveolar ridge promotion[J]. Mater Sci Eng C Mater Biol Appl, 2020, 116: 111158.
[37] Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC)[J]. Adv Drug Deliv Rev, 2001, 48(2/3):139-157.
[38] Lin CC, Metters AT. Hydrogels in controlled release formulations: Network design and mathematical modeling[J].Adv Drug Deliv Rev, 2006, 58(12/13):1379-1408.
[39] 何丽华, 闵洁, 郑荣, 等. 基于pH敏感型葡聚糖水凝胶微球的药物载体[J]. 精细化工, 2020, 37(3):494-499.
[40] 姚鹏磊, 陈鑫, 颜涛, 等. 透明质酸在常见恶性肿瘤中的研究进展[J]. 现代肿瘤医学, 2021, 29(12):2170-2173.
[41] Yu JC, Zhang YQ, Sun WJ, et al. Endosome-mimicking nanogels for targeted drug delivery[J]. Front Bioeng Biotechnol, 2016, 4: 1196.
[42] Pagano C, Giovagnoli S, Perioli L, et al. Development and characterization of mucoadhesive-thermoresponsive gels for the treatment of oral mucosa diseases[J]. Eur J Pharm Sci, 2020, 142: 105125.
[43] Missirlis D, Tirelli N, Hubbell JA. Amphiphilic hydrogel nanoparticles.preparation, characterization, and preliminary assessment as new colloidal drug carriers[J]. Langmuir, 2005, 21(6):2605-2613.
[44] Jin X, Fu Q, Gu ZH, et al. Chitosan/PDLLA-PEG-PDLLA solution preparation by simple stirring and formation into a hydrogel at body temperature for whole wound healing[J]. Int J Biol Macromol, 2021, 184: 787-796.
[45] Chen H, Cheng RY, Zhao X, et al. An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair[J]. NPG Asia Mater, 2019, 11(1):1-12.
[46] Arafa AA, Nada AA, Ibrahim AY, et al. Preparation and characterization of smart therapeutic pH-sensitive wound dressing from red cabbage extract and chitosan hydrogel[J]. Int J Biol Macromol, 2021, 182: 1820-1831.
[47] Dou XQ, Feng CL. Amino acids and peptide-based supramolecular hydrogels for three-dimensional cell culture[J/OL]. Adv Mater, 2017, 29(16).(2017-01-23)[2017-04-16]. DOI:10.1002/adma.201604062.
[48] Alshehri S, Susapto HH, Hauser CAE. Scaffolds from self-assembling tetrapeptides support 3D spreading, osteogenic differentiation, and angiogenesis of mesenchymal stem cells[J]. Biomacromolecules, 2021, 22(5):2094-2106.