Application and progress of intelligent responsive hydrogels in articular cartilage injury repair_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XU Qingyu , ZHANG Baojian , LI Hongri , LIU Chengri , BI Shuhao , YANG Zhixiang ,  LIU Yanqun

Orthopedic Diagnosis and Treatment Center, Yanbian University Hospital (Yanbian Hospital), Yanji Jilin, 133000, P. R. China;

Corresponding author：

LIU Yanqun, Email: 13844312816@163.com

Keywords：

Intelligent responsive hydrogel; response principle; cartilage injury; repair

DOI：

10.7507/1002-1892.202411015

Video：

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Objective To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury. Methods The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad. Results The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries. Conclusion Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.

Citation： XU Qingyu, ZHANG Baojian, LI Hongri, LIU Chengri, BI Shuhao, YANG Zhixiang, LIU Yanqun. Application and progress of intelligent responsive hydrogels in articular cartilage injury repair. Chinese Journal of Reparative and Reconstructive Surgery, 2025, 39(2): 250-256. doi: 10.7507/1002-1892.202411015 Copy

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1. 蒋宁, 徐桂军, 李浩民, 等. 距骨骨软骨损伤的外科治疗进展. 中国修复重建外科杂志, 2024, 38(3): 373-379.
2. Whyte GP, Bizzoco L, Gobbi A. One-step cartilage repair of full-thickness knee chondral lesions using a hyaluronic acid-based scaffold embedded with bone marrow aspirate concentrate: Long-term outcomes after mean follow-up duration of 14 years. Am J Sports Med, 2024, 52(14): 3561-3568.
3. Brittberg M. Treatment of knee cartilage lesions in 2024: From hyaluronic acid to regenerative medicine. J Exp Orthop, 2024, 11(2): e12016. doi: 10.1002/jeo2.12016.
4. Sharma V, Sakhalkar U, Nadkarni P, et al. Cytoprotective effect of growth factors derived from platelets on corticosteroid-treated primary anterior cruciate ligament-derived stromal cells and chondrocytes. Cureus, 2024, 16(7): e65566. doi: 10.7759/cureus.65566.
5. 杨星, 周明旺, 王晓萍, 等. 干细胞修复软骨损伤治疗膝骨关节炎的机制与临床研究进展. 中国骨质疏松杂志, 2024, 30(10): 1466-1471.
6. Rahvar TP, Abdekhodaie JM, Jooybar E, et al. An enzymatically crosslinked collagen type Ⅱ/hyaluronic acid hybrid hydrogel: A biomimetic cell delivery system for cartilage tissue engineering. Int J Biol Macromol, 2024, 279(P1): 134614. doi: 10.1016/j.ijbiomac.2024.134614.
7. Yuan X, Wan J, Yang Y, et al. Thermosensitive hydrogel for cartilage regeneration via synergistic delivery of SDF-1α like polypeptides and kartogenin. Carbohydr Polym, 2023, 304: 120492. doi: 10.1016/j.carbpol.2022.120492.
8. Ross AK, Ferati RS, Alaia JM, et al. Current and emerging techniques in articular cartilage repair. Bull Hosp Jt Dis (2013), 2024, 82(1): 91-99.
9. Khajouei S, Ravan H, Ebrahimi A. DNA hydrogel-empowered biosensing. Adv Colloid Interface Sci, 2020, 275: 102060. doi: 10.1016/j.cis.2019.102060.
10. Cao H, Duan LX, Zhang Y, et al. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct Target Ther, 2021, 6(1): 426-426.
11. Cheng W, Ding Z, Zheng X, et al. Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration. Biomater Sci, 2020, 8(9): 2537-2548.
12. 陆怡雨, 李昊. 智能水凝胶在口腔医学领域的应用. 南京医科大学学报 (自然科学版), 2022, 42(8): 1192-1196,1200.
13. 杨跃娜, 胡旭芳, 刘玉珊, 等. 智能水凝胶世界. 大学化学, 2024, 39(5): 172-183.
14. Hoang Thi TT, Sinh LH, Huynh DP, et al. Self-assemblable polymer smart-blocks for temperature-induced injectable hydrogel in biomedical applications. Front Chem, 2020, 8: 19. doi: 10.3389/fchem.2020.00019.
15. Mahinroosta M, Farsangi JZ, Allahverdi A, et al. Hydrogels as intelligent materials: A brief review of synthesis, properties and applications. Materials Today Chemistry, 2018, 8: 42-55.
16. 朱本舜, 郑睿夫, 周亚坤, 等. 医用自剥离水凝胶敷料的研究进展. 现代化工, 2024, 44(4): 34-39, 44.
17. Tang Y, Wang J, Qiu H, et al. The chondrogenic differentiation of BMSCs in collagen hydrogels and the effect of MMPs among cell-material interactions. Collagen and Leather, 2024, 6(1): 31-46.
18. 王勇, 姚子昂, 吴海歌. 壳聚糖温敏水凝胶在骨组织工程中的研究进展. 化工新型材料, 2022, 50(S1): 13-19.
19. 郭伟成, 廖元太, 张洪玉. 润滑水凝胶涂层研究进展. 清华大学学报(自然科学版), 2024, 64(3): 381-392.
20. Jiang Z, Qin S, Wang W, et al. Investigating the anti-inflammatory and bone repair-promoting effects of an injectable porous hydrogel containing magnesium ions in a rat periodontitis mode. Smart Materials in Medicine, 2024, 5(2): 207-220.
21. Shi F, Xiao D, Zhang C, et al. The effect of macropore size of hydroxyapatite scaffold on the osteogenic differentiation of bone mesenchymal stem cells under perfusion culture. Regen Biomater, 2021, 8(6): rbab050. doi: 10.1093/rb/rbab050.
22. Elsheikh M, Kishida R, Hayashi K, et al. Effects of pore interconnectivity on bone regeneration in carbonate apatite blocks. Regen Biomater, 2022, 9(1): rbac010. doi: 10.1093/rb/rbac010.
23. Huang Z, Liu C, Zheng G, et al. Articular cartilage regeneration via induced chondrocyte autophagy by sustained release of leptin inhibitor from thermo-sensitive hydrogel through STAT3/REDD1/mTORC1 cascade. Adv Healthc Mater, 2023, 12(30): e2302181. doi: 10.1002/adhm.202302181.
24. Hasani-Sadrabadi MM, Sarrion P, Pouraghaei S, et al. An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats. Sci Transl Med, 2020, 12(534): eaay6853. doi: 10.1126/scitranslmed.aay6853.
25. Ao Y, Tang W, Tan H, et al. Hydrogel composed of type Ⅱ collagen, chondroitin sulfate and hyaluronic acid for cartilage tissue engineering. Biomed Mater Eng, 2022, 33(6): 515-523.
26. 张新威. 3D打印rGO复合水凝胶支架用于多细胞递送和骨修复的研究. 长春: 吉林大学, 2023.
27. Tian Y, Cui Y, Ren G, et al. Dual-functional thermosensitive hydrogel for reducing infection and enhancing bone regeneration in infected bone defects. Mater Today Bio, 2024, 25: 100972. doi: 10.1016/j.mtbio.2024.100972.
28. Hafezi M, Nouri Khorasani S, Zare M, et al. Advanced hydrogels for cartilage tissue engineering: Recent progress and future directions. Polymers (Basel), 2021, 13(23): 4199. doi: 10.3390/polym13234199.
29. Chen Z, Yang X, Liu X, et al. A thermodynamic theory coupling photo-chemo-mechano interactions for light-responsive hydrogel. Journal of the Mechanics and Physics of Solids, 2024, 188: 105677-105693.
30. Liu XY, Yang QS, Rao W. A photo-mechanical coupling theory for photoisomerization hydrogel considering the distribution state of molecular chains. International Journal of Solids and Structures, 2023, 283: 112474-112489.
31. 张恒杰, 柳坤锐, 陈显春, 等. 光响应智能生物粘附材料的设计与应用. 化学学报, 2023, 81(12): 1739-1753.
32. Tsegay F, Elsherif M, Butt H. Smart 3D printed hydrogel skin wound bandages: A review. Polymers (Basel), 2022, 14(5): 1012. doi: 10.3390/polym14051012.
33. Zhang W, Xue W, Jia Z, et al. Photo-driven dynamic hydrogel modulates bone marrow mesenchymal stem cells behavior for enhanced cartilage regeneration. Chemical Engineering Journal, 2024, 484: 149689-149699.
34. 刘晓雨, 张辛芮, 张烨华, 等. 自黏附、近红外光响应水凝胶的制备及药物释放性能研究. 化学通报, 2024, 87(7): 850-856.
35. Diego T, Lorenzo V, Elena G, et al. Visible light-mediated cross-linking of injectable gellan gum hydrogels embedding human chondrocytes. Carbohydrate Polymer Technologies and Applications, 2023, 6: 100382-100396.
36. 薛春宇, 陈国強, 袁俊虎, 等. 应用天然水凝胶修复关节软骨损伤的研究进展. 生物骨科材料与临床研究, 2024, 21(1): 56-60, 70.
37. Zhao X, Javed B, Tian F, et al. Hydrogel on a smart nanomaterial interface to carry therapeutics for digitalized glioma treatment. Gels, 2022, 8(10): 664. doi: 10.3390/gels8100664.
38. Gao L, Beninatto R, Oláh T, et al. A photopolymerizable biocompatible hyaluronic acid hydrogel promotes early articular cartilage repair in a minipig model in vivo. Adv Healthc Mater, 2023, 12(26): e2300931. doi: 10.1002/adhm.202300931.
39. 王泽文, 李陈致, 刘家河, 等. 软骨支架材料的制备方法及优缺点. 中国组织工程研究, 2024, 28(15): 2404-2409.
40. Khanmohammadi M, Jalessi M, Asghari A. Biomimetic hydrogel scaffolds via enzymatic reaction for cartilage tissue engineering. BMC Res Notes, 2022, 15(1): 174. doi: 10.1186/s13104-022-06060-w.
41. Kim J, Park S, Park YJ, et al. Dual-phase blocks for regeneration of critical-sized bone defects. Nano Today, 2024, 54: 102120-102133.
42. Naghizadeh Z, Karkhaneh A, Nokhbatolfoghahaei H, et al. Cartilage regeneration with dual-drug-releasing injectable hydrogel/microparticle system: In vitro and in vivo study. J Cell Physiol, 2021, 236(3): 2194-2204.
43. Alqurashi Y, Elsherif M, Hendi A, et al. Optical hydrogel detector for pH measurements. Biosensors (Basel), 2022, 12(1): 40. doi: 10.3390/bios12010040.
44. 郑月丹, 王晓玲, 冯俊峰, 等. 刺激响应型可注射水凝胶在药物控释领域的研究进展. 高分子材料科学与工程, 2024, 40(9): 164-172.
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Chinese Journal of Reparative and Reconstructive Surgery

Application and progress of intelligent responsive hydrogels in articular cartilage injury repair

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