综述

骨关节炎治疗用水凝胶研究进展

  • 焦涵 ,
  • 吴承伟 ,
  • 迟海涛 ,
  • 张伟
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  • 1. 大连理工大学工程力学系生物与纳米力学实验室,工业装备结构分析国家重点实验室,大连 116024
    2. 大连大学附属新华医院神经内科,大连 116021
焦涵,硕士研究生,研究方向为生物医用水凝胶,电子信箱:13105449230@163.com

收稿日期: 2022-07-16

  修回日期: 2022-11-16

  网络出版日期: 2023-09-28

基金资助

国家重点研发计划项目(2022YFE0115400,2018YFA0704103,2018YFA0704104);教育部“春晖计划”合作科研项目(HZKY20220413);中央高校基本科研业务费项目(DUT21TD105, DUT22YG123)

Recent advances in hydrogel for osteoarthritis treatment

  • JIAO Han ,
  • WU Chengwei ,
  • CHI Haitao ,
  • ZHANG Wei
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  • 1. State Key Laboratory of Structure Analysis for Industrial Equipment, Biomechanics and Nanomechanics Laboratory in Department of Engineering Mechanics, Dalian University of Technology, Dalian 116024, China
    2. Department of Neurology, Xinhua Hospital Affiliated to Dalian University, Dalian 116021, China

Received date: 2022-07-16

  Revised date: 2022-11-16

  Online published: 2023-09-28

摘要

骨关节炎(OA)是易发于中老年群体的一种退行性病变,侵蚀关节软骨及其附属组织,严重影响患者的生活。水凝胶生物相容性好、力学性能优良,由其制成的功能性水凝胶可以弥补目前OA常用疗法中药物作用时间短、难以实现软骨组织再生等缺点,受到广泛的关注。总结了水凝胶在OA药物治疗、软骨缺损修复、关节滑液修复等方面的研究进展,探讨了药物释放水凝胶消炎止疼原理和药物缓释机理、软骨缺损修复水凝胶的修复机理以及关节润滑水凝胶的润滑机制。探讨了水凝胶治疗OA中存在的问题及其发展方向。

本文引用格式

焦涵 , 吴承伟 , 迟海涛 , 张伟 . 骨关节炎治疗用水凝胶研究进展[J]. 科技导报, 2023 , 41(18) : 72 -83 . DOI: 10.3981/j.issn.1000-7857.2023.18.010

Abstract

Osteoarthritis (OA) is a degenerative disease that is prone to occur in the middle-aged and elderly groups. It can erode articular cartilage and its affiliated organization, and seriously affect the life of patients. Hydrogels have good biocompatibility and excellent mechanical properties. Functional hydrogels can make up for the shortcomings of short drug action time and the difficulties to cure OA in common therapy approaches. In this article, we review the recent advances of hydrogel as a carrier to treat osteoarthritis from the aspects of drug treatment of osteoarthritis, cartilage defect repair, and synovial fluid repair. The anti-inflammatory and analgesic mechanism of drug release hydrogel, the mechanism of cartilage repair of cartilage defect repair hydrogel and the joint lubrication mechanism of joint lubrication hydrogel were discussed. On these bases, we also summarize the existing problems and propose further development direction of hydrogel in the treatment of OA.

参考文献

[1] Martel-Pelletier J, Barr A, Cicuttini F, et al. Osteoarthritis[J]. Nature Reviews Disease Primers, 2016, 2(1): 16072.
[2] 林琳, 程珂, 沈雪勇. 近5年低强度激光针灸治疗膝骨关节炎的临床研究综述[J]. 中华中医药学刊, 2020, 38(5): 104-108.
[3] 余红秀, 徐建圆, 蒋臻, 等. 中药热敷配合中频脉冲治疗仪治疗膝骨关节炎 41 例[J]. 中国中医药科技, 2022, 29(5): 840-842.
[4] Warren D S, Sutherland S P H, Kao J Y, et al. The preparation and simple analysis of a clay nanoparticle composite hydrogel[J]. Journal of Chemical Education, 2017, 94(11): 1772-1779.
[5] 吴维, 吴迪, 马珊珊, 等. 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.
[6] Bowman S, Awad M E, Hamrick M W, et al. Recent advances in hyaluronic acid based therapy for osteoarthritis[J]. Clinical and Translational Medicine, 2018, 7(1): e6.
[7] 朱益锐, 蔡志祥, 郭亚龙, 等. 基于透明质酸构建的功能材料及其在生物医药领域中的应用[J]. 功能高分子学报, 2021, 34(1): 26-48.
[8] Lindqvist U, Tolmachev V, Kairemo K, et al. Elimination of stabilised hyaluronan from the knee joint in healthy men[J]. Clinical Pharmacokinetics, 2002, 41(8): 603-613.
[9] 李辉, 谢兴文, 李建国, 等. NF-κB信号通路在骨关节炎中的作用[J]. 生命的化学, 2021, 41(9): 1915-1919.
[10] Parameswaran V, Hild C, Eichner G, et al. Interleukin-1 induces the release of lubricating phospholipids from human osteoarthritic fibroblast-like synoviocytes[J]. International Journal of Molecular Sciences, 2022, 23(5): 2409.
[11] 陈德胜, 张晨, 宋国瑞, 等 . TNF-α、MMP-9在 OA 滑膜组织中表达及其意义[J]. 宁夏医学杂志, 2020, 42(11): 965-968+960.
[12] Cheng X F, Zhang L, Zhang K, et al. Circular RNA VMA21 protects against intervertebral disc degeneration through targeting MiR-200c and X linked inhibitor-of-apoptosis protein[J]. Annals of the Rheumatic Diseases, 2018, 77(5): 770-779.
[13] 林洁, 叶锦霞, 陈俊, 等 . lncRNA在骨关节炎发病及病变机制中的可能作用[J]. 风湿病与关节炎, 2017, 6(8): 53-55+63.
[14] Alcaraz M J, Megías J, García-Arnandis I, et al. New molecular targets for the treatment of osteoarthritis[J]. Biochemical Pharmacology, 2010, 80(1): 13-21.
[15] 王培, 楚天舒, 阎磊, 等 . COX-2 mRNA 在膝骨关节炎病变过程中的作用研究[J]. 临床医学工程, 2019, 26(4): 477-478.
[16] Westin C B, Nagahara M H T, Decarli M C, et al. Development and characterization of carbohydrate-based thermosensitive hydrogels for cartilage tissue engineering[J]. European Polymer Journal, 2020, 129: 109637.
[17] Cai Y P, López-Ruiz E, Wengel J, et al. A hyaluronic acid-based hydrogel enabling CD44-mediated chondrocyte binding and gapmer oligonucleotide release for modulation of gene expression in osteoarthritis[J]. Journal of Controlled Release, 2017, 253: 153-159.
[18] Kulsirirat T, Sathirakul K, Kamei N, et al. The in vitro and in vivo study of novel formulation of androgra‐pholide PLGA nanoparticle embedded into gelatin-based hydrogel to prolong delivery and extend residence time in joint[J]. International Journal of Pharmaceutics, 2021, 602: 120618.
[19] Chen S J, Luo Z H, Chen X G. Andrographolide miti‐gates cartilage damage via miR‐27‐3p‐modulated matrix metalloproteinase13 Repression[J]. The Journal of Gene Medicine, 2020, 22(8): e3187.
[20] Wang R L, Li J W, Xu X Q, et al. Andrographolide attenuates synovial inflammation of osteoarthritis by interacting with tumor necrosis factor receptor 2 trafficking in a rat model[J]. Journal of Orthopaedic Translation, 2021, 29: 89-99.
[21] Li B, Jiang T M, Liu H, et al. Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1-Nrf2-Are signaling pathway[J]. Journal of Cellular Physiology, 2018, 234(1): 561-571.
[22] Tsubosaka M, Kihara S, Hayashi S, et al. Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model[J]. Journal of Orthopaedic Research, 2020, 38(10): 2157-2169.
[23] Hanafy A S, El-Ganainy S O. Thermoresponsive hyalomer intra-articular hydrogels improve monoiodoacetate-induced osteoarthritis in rats[J]. International Journal of Pharmaceutics, 2020, 573: 118859.
[24] Diaz-Rodriguez P, Cibrán M, Vázquez J, et al. Targeting joint inflammation for osteoarthritis management through stimulus-sensitive hyaluronic acid based intra-articular hydrogels[J]. Materials Science & Engineering C, 2021, 128: 112254.
[25] Xia C, Chen P F, Mei S, et al. Photo-crosslinked HAMA hydrogel with cordycepin encapsulated chitosan microspheres for osteoarthritis treatment[J]. Oncotarget, 2016, 8(2): 2835-2849.
[26] Chen P F, Mei S, Xia C, et al. The amelioration of cartilage degeneration by photo-crosslinked GelHA hydrogel and crizotinib encapsulated chitosan microspheres[J]. Oncotarget, 2017, 8(18): 30235-30251.
[27] Jain E, Chinzei N, Blanco A, et al. Platelet‐rich plasma released from polyethylene glycol hydrogels exerts beneficial effects on human chondrocytes[J]. Journal of Orthopaedic Research, 2019, 37(11): 2401-2410.
[28] Agas D, Laus F, Lacava G, et al. Thermosensitive hybrid hyaluronan/p(HPMAm‐lac)‐PEG hydrogels enhance cartilage regeneration in a mouse model of osteoarthritis[J]. Journal of Cellular Physiology, 2019, 234(11): 20013-20027.
[29] Mok S W, Fu S C, Cheuk Y C, et al. Intra-articular delivery of quercetin using thermosensitive hydrogel attenuate cartilage degradation in an osteoarthritis rat model[J]. Cartilage, 2018, 11(4): 490-499.
[30] Holyoak D T, Wheeler T A, Van der Meulen M C H, et al. Injectable mechanical pillows for attenuation of load-induced post-traumatic osteoarthritis[J]. Regenerative Biomaterials, 2019, 6(4): 211-219.
[31] Zhang T T, Chen S Q, Dou H B, et al. Novel glucosamine-loaded thermosensitive hydrogels based on poloxamers for osteoarthritis therapy by intra-articular injection[J]. Materials Science and Engineering: C, 2021, 118: 111352.
[32] Zhang Z Q, Wang X G, Li P S, et al. Transdermal delivery of buprenorphine from reduced graphene oxide laden hydrogel to treat osteoarthritis[J]. Journal of Biomaterials Science, Polymer Edition, 2021, 32(7): 874-885.
[33] 林涛, 陈竹, 袁德超, 等 . 关节软骨缺损修复治疗的研究进展[J]. 西部医学, 2015, 27(4): 631-634.
[34] 李海鹏, 刘玉杰 . 关节软骨损伤治疗的最新进展[J].中国矫形外科杂志, 2006(14): 1076-1078.
[35] Pascual-Garrido C, Rodriguez-Fontan F, Aisenbrey E A, et al. Current and novel injectable hydrogels to treat focal chondral lesions: Properties and applicability[J]. Journal of Orthopaedic Research, 2018, 36(1): 64-75.
[36] 黄玉文, 秦煜, 李书振. 间充质干细胞治疗骨性关节炎的研究进展[J]. 广西医学, 2022, 44(3): 338-342.
[37] Makris E A, Gomoll A H, Malizos K N, et al. Repair and tissue engineering techniques for articular cartilage[J]. Nature Reviews. Rheumatology, 2015, 11(1): 21-34.
[38] Pittenger M F, Mackay A M, Beck S C, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science, 1999, 284(5411): 143-147.
[39] 李春霖, 邓国英, 王秋根, 等 . 改善成骨微环境促进间充质干细胞成骨分化研究进展[J]. 国际骨科学杂志, 2018, 39(5): 282-286.
[40] 刘秀华, 唐朝枢 . 干细胞的旁分泌和自分泌功能——基础与临床研究的新视角[J]. 生理科学进展, 2008(3): 196-202.
[41] Jeong S Y, Kim D H, Ha J, et al. Thrombospondin-2 secreted by human umbilical cord blood-derived mesenchymal stem cells promotes chondrogenic differentiation.[J]. Stem Cells, 2013, 31(10): 2136-2148.
[42] Zhang S, Chu W C, Lai R C, et al. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration[J]. Osteoarthritis and Cartilage, 2016, 24(12): 2135-2140.
[43] 周绪昌, 李慧, 邹军, 等 . 外泌体对骨关节炎的影响[J]. 中国细胞生物学学报, 2018, 40(8): 1402-1407.
[44] Wang Y F, Yu D S, Liu Z M, et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix[J]. Stem Cell Research & Therapy, 2017, 8(1): 189.
[45] Yang Y L, Zhu Z C, Gao R Z, et al. Controlled release of MSC-derived small extracellular vesicles by an injectable diels-alder crosslinked hyaluronic Acid/PEG hydrogel for osteoarthritis improvement[J]. Acta Biomaterialia, 2021, 128: 163-174.
[46] Zhang S, Chuah S J, Lai R C, et al. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity[J]. Biomaterials, 2018, 156: 16-27.
[47] Park Y B, Ha C W, Lee C H, et al. Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended fol‐
low-up[J]. Stem Cells Translational Medicine, 2016, 6(2): 613-621.
[48] Wang A T, Zhao M, Feng Y, et al. Multifaceted optimization of MSC-based formulation upon sodium iodoacetate-induced osteoarthritis models by combining advantageous HA/PG hydrogel and fluorescent tracer[J]. Stem Cells International, 2021, 2021: 1-13.
[49] Kilmer C E, Battistoni C M, Cox A, et al. Collagen type I and II blend hydrogel with autologous mesenchymal stem cells as a scaffold for articular cartilage defect repair[J]. ACS Biomaterials Science & Engineering, 2020, 6(6): 3464-3476.
[50] Luo C H, Guo A, Zhao Y F, et al. A high strength, low friction, and biocompatible hydrogel from PVA, chitosan
and sodium alginate for articular cartilage[J]. Carbohydrate Polymers, 2022, 286: 119268.
[51] Beck E C, Barragan M, Tadros M H, et al. Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel[J]. Acta Biomaterialia, 2016, 38: 94-105.
[52] Li H, Li J M, Li T, et al. Macroporous polyvinyl alcohol-tannic acid hydrogel with high strength and toughness for cartilage replacement[J]. Journal of Materials Science, 2022, 57(17): 8262-8275.
[53] Li H, Wu C W, Wang S, et al. Mechanically strong poly(vinyl alcohol) hydrogel with macropores and high porosity[J]. Materials Letters, 2020, 266(C): 127504.
[54] Thangprasert A, Tansakul C, Thuaksubun N, et al. Mimicked hybrid hydrogel based on gelatin/PVA for tissue engineering in subchondral bone interface for osteoarthritis Surgery[J]. Materials &Amp; Design, 2019, 183: 108-113.
[55] Li J M, Li H, Wu C W, et al. PVA-AAm-AG multi-network hydrogel with high mechanical strength and cell adhesion[J]. Polymer, 2022, 247: 124786.
[56] Kim B J, Arai Y, Choi B, et al. Restoration of articular osteochondral defects in rat by a Bi-layered hyaluronic acid hydrogel plug with TUDCA-PLGA microsphere[J]. Journal of Industrial and Engineering Chemistry, 2018, 61: 295-303.
[57] Hua Y J, Xia H T, Jia L T, et al. Ultrafast, tough, and adhesive hydrogel based on hybrid photocrosslinking for articular cartilage repair in water-filled arthroscopy[J]. Science Advances, 2021, 7(35): eabg0628.
[58] Bose S, Roy M, Bandyopadhyay A. Recent advances in bone tissue engineering scaffolds[J]. Trends in Biotechnology, 2012, 30(10): 546-554.
[59] 潘建锋, 郭常安, 阎作勤. 关节软骨原位再生研究进展[J]. 国际骨科学杂志, 2012, 33(1): 4.
[60] 汤凯, 招文华, 尚奇, 等 . 浓缩生长因子干预大鼠骨髓间充质干细胞的增殖、成骨分化及迁移[J]. 中国组织工程研究, 2022, 26(31): 4935-4939.
[61] Li H, Li J M, Yu S B, et al. The mechanical properties of tibiofemoral and patellofemoral articular cartilage in compression depend on anatomical regions[J]. Scientific Reports, 2021, 11(1): 6128.
[62] Henrotin Y, Rocasalbas G, Chausson M, et al. An innovative non-animal chitosan hydrogel is able to restore the rheology of osteoarthritis synovial fluid ex vivo[J]. Osteoarthritis and Cartilage, 2017, 25: 405.
[63] 李月, 郭俊德, 王伟, 等 . PCEC 水凝胶缓释 BSA/CS 的润滑性能[J]. 中国表面工程, 2017, 30(5): 74-80.
[64] Yang F C, Zhao J C, Koshut W J, et al. A synthetic hydrogel composite with the mechanical behavior and durability of cartilage[J]. Advanced Functional Materials, 2020, 30(36): 2003451.
[65] Cai Z X, Zhang H, Wei Y, et al. Shear-thinning hyaluronan-based fluid hydrogels to modulate viscoelastic properties of osteoarthritis synovial fluids[J]. Biomaterials Sci‐ence, 2019, 7(8): 3143-3157.
[66] Han Y, Yang J L, Zhao W W, et al. Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis[J]. Bioactive Materials, 2021, 6(10): 3596-3607.
[67] Lei Y T, Wang Y P, Shen J L, et al. Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis[J]. Science Advances, 2022, 8(5): eabl6449.
[68] Yang J L, Han Y, Lin J W, et al. Ball-bearing-inspired polyampholyte-modified microspheres as bio-lubricants attenuate osteoarthritis[J]. Small, 2020, 16(44): e2004519.
[69] Ji X L, Yan Y F, Sun T, et al. Glucosamine sulphate-loaded distearoyl phosphocholine liposomes for osteoarthritis treatment: combination of sustained drug release and improved lubrication[J]. Biomaterials Science, 2019, 7(7): 2716-2728.
[70] Brody L T, Knee osteoarthritis: Clinical connections to articular cartilage structure and function[J]. Physical Therapy in Sport, 2015, 16(4): 301-316.
[71] Zhang Q, Lu H X, Kawazoe N, et al. Pore size effect of collagen scaffolds on cartilage regeneration[J]. Acta Biomaterialia, 2014, 10(5): 2005-2013.
[72] 张姝江, 王瑛, 陈艺, 等 . 生物力学在关节软骨修复中的作用[J]. 中华关节外科杂志(电子版), 2018, 12(6): 842-848.
[73] 阮春标, 胡经纬, 袁恒迪, 等 . 可用于人工关节润滑的水凝胶蠕变缓释性能及理论模型[J]. 西安交通大学学报, 2022, 56(6): 97-103.
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