Research progress of in situ crosslinked hydrogels as vitreous substitutes_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Wei , He Zhen , Zhang Limin , Liu Jingyao , Liu Boshi ,  Li Xiaorong

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China;

Corresponding?author：

Li Xiaorong, Email: iiitc1989@163.com

Keywords：

Vitreous; Vitreous substitutes; Hydrogels; In situ crosslinked; Review

DOI：

10.3760/cma.j.cn511434-20251029-00475

Video：

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Abstract Full text Figures/Tables Video References Cited by

The vitreous body is a gel-like ocular tissue essential for maintaining intraocular structure and visual function. Degeneration of the vitreous, including age-related liquefaction and structural collapse, can result in vitreoretinal disorders that require vitrectomy with substitute materials. Conventional vitreous substitutes, such as gases and silicone oils, are limited by single-functionality, suboptimal biocompatibility, and complications including cataract formation and elevated intraocular pressure. In contrast, hydrogels, owing to their high water content, favorable biocompatibility, tunable physicochemical properties, and potential for sustained and controlled drug delivery, have emerged as highly promising vitreous substitutes. This review summarizes recent advances in in situ crosslinked hydrogels for vitreous replacement, focusing on chemically crosslinked and physically crosslinked systems. Chemically crosslinked hydrogels offer good stability and biodegradability through covalent network formation, although precise control of degradation behavior and byproduct safety remains challenging. Physically crosslinked hydrogels, formed via physical or supramolecular interactions, exhibit low toxicity and self-healing capability but often suffer from rapid degradation, necessitating combined crosslinking strategies to prolong intraocular residence. Furthermore, drug-loaded in situ hydrogels incorporating anti-inflammatory, antioxidant, or anti-proliferative vitreoretinopathy agents represent a shift from passive fillers toward active therapeutic platforms. Future studies should further optimize hydrogel performance and systematically evaluate their long-term biological effects within the intraocular microenvironment to facilitate clinical translation.

1.	Monteiro JP, Santos FM, Rocha AS, et al. Vitreous humor in the pathologic scope: insights from proteomic approaches[J]. Proteomics Clin Appl, 2015, 9(1-2): 187-202. DOI: 10.1002/prca.201400133.
2.	Scott JE. The chemical morphology of the vitreous[J]. Eye (Lond), 1992, 6(Pt 6): 553-555. DOI: 10.1038/eye.1992.120.
3.	Singh A, Boulton M, Lane C, et al. Inhibition of microvascular endothelial cell proliferation by vitreous following retinal scatter photocoagulation[J]. Br J Ophthalmol, 1990, 74(6): 328-332. DOI: 10.1136/bjo.74.6.328.
4.	Purtskhvanidze K, Hillenkamp J, Tode J, et al. Thinning of inner retinal layers after vitrectomy with silicone oil versus gas endotamponade in eyes with macula-off retinal detachment[J]. Ophthalmologica, 2017, 238(3): 124-132. DOI: 10.1159/000477743.
5.	Feng X, Li C, Zheng Q, et al. Risk of silicone oil as vitreous tamponade in pars plana vitrectomy: a systematic review and meta-analysis[J]. Retina, 2017, 37(11): 1989-2000. DOI: 10.1097/iae.0000000000001553.
6.	Haave H, Petrovski B, Zaj?c M, et al. Outcomes from the retrospective multicenter cross-sectional study on lamellar macular hole surgery[J]. Clin Ophthalmol, 2022, 16: 1847-1860. DOI: 10.2147/opth.S351932.
7.	Liu Z, Liow SS, Lai SL, et al. Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade[J]. Nat Biomed Eng, 2019, 3(8): 598-610. DOI: 10.1038/s41551-019-0382-7.
8.	Singh SR, Dhurandhar D, Chhablani J. Sandwich technique using a combination of perfluoropropane and silicone oil for inferior retinal detachment[J]. Indian J Ophthalmol, 2018, 66(7): 988-990. DOI: 10.4103/ijo.IJO_1294_17.
9.	Gao QY, Fu Y, Hui YN. Vitreous substitutes: challenges and directions[J]. Int J Ophthalmol, 2015, 8(3): 437-440. DOI: 10.3980/j.issn.2222-3959.2015.03.01.
10.	Gozawa M, Kanamoto M, Ishida S, et al. Evaluation of intraocular gas using magnetic resonance imaging after pars plana vitrectomy with gas tamponade for rhegmatogenous retinal detachment[J/OL]. Sci Rep, 2020, 10(1): 1521[2020-01-30]. https://pubmed.ncbi.nlm.nih.gov/32001793/. DOI: 10.1038/s41598-020-58508-3.
11.	Kim SS, Smiddy WE, Feuer WJ, et al. Outcomes of sulfur hexafluoride (SF6) versus perfluoropropane (C3F8) gas tamponade for macular hole surgery[J]. Retina, 2008, 28(10): 1408-1415. DOI: 10.1097/IAE.0b013e3181885009.
12.	Giansanti F, Tartaro R, Caporossi T, et al. An internal limiting membrane plug and gas endotamponade for recurrent or persistent macular holeJ/OL]. J Ophthalmol, 2019, 2019: 6051724[2019-04-07]. https://pubmed.ncbi.nlm.nih.gov/30956814/. DOI: 10.1155/2019/6051724.
13.	Su X, Tan MJ, Li Z, et al. Recent progress in using biomaterials as vitreous substitutes[J]. Biomacromolecules, 2015, 16(10): 3093-3102. DOI: 10.1021/acs.biomac.5b01091.
14.	Yadav I, Purohit SD, Singh H, et al. Vitreous substitutes: an overview of the properties, importance, and development[J]. J Biomed Mater Res B Appl Biomater, 2021, 109(8): 1156-1176. DOI: 10.1002/jbm.b.34778.
15.	Marti M, Walton R, B?ni C, et al. Increased intraocular pressure is a risk factor for unexplained visual loss during silicone oil endotamponade[J]. Retina, 2017, 37(12): 2334-2340. DOI: 10.1097/iae.0000000000001492.
16.	Davo-Cabrera JM, Lanzagorta-Aresti A, Alcocer Yuste P. A novel surgical technique for ahmed valves in refractory glaucoma with silicone oil endotamponade[J/OL]. J Glaucoma, 2017, 26(10): e232-e235[2017-10-01]. https://pubmed.ncbi.nlm.nih.gov/28816817/. DOI: 10.1097/ijg.0000000000000737.
17.	Valentín-Bravo FJ, García-Onrubia L, Andrés-Iglesias C, et al. Complications associated with the use of silicone oil in vitreoretinal surgery: a systemic review and meta-analysis[J/OL]. Acta Ophthalmol, 2022, 100(4): e864-e880[2021-11-29]. https://pubmed.ncbi.nlm.nih.gov/34846097/. DOI: 10.1111/aos.15055.
18.	Naik K, Du Toit LC, Ally N, et al. Advances in polysaccharide- and synthetic polymer-based vitreous substitutes[J/OL]. Pharmaceutics, 2023, 15(2): 566[2023-02-08]. https://pubmed.ncbi.nlm.nih.gov/36839888/. DOI: 10.3390/pharmaceutics15020566.
19.	Tobalem SJ, Weinberger A, Kropp M, et al. Chorioretinal toxicity of perfluorooctane (Ala OCTA): results from 48 surgical procedures in geneva[J]. Am J Ophthalmol, 2020, 218: 28-39. DOI: 10.1016/j.ajo.2020.05.014.
20.	Januschowski K, Irigoyen C, Pastor JC, et al. Retinal toxicity of medical devices used during vitreoretinal surgery: a critical overview[J]. Ophthalmologica, 2018, 240(4): 236-243. DOI: 10.1159/000488504.
21.	Qu S, Tang Y, Ning Z, et al. Desired properties of polymeric hydrogel vitreous substitute[J/OL]. Biomed Pharmacother, 2024, 172: 116154[2024-02-01]. https://pubmed.ncbi.nlm.nih.gov/38306844/. DOI: 10.1016/j.biopha.2024.116154.
22.	Kopecek J. Hydrogel biomaterials: a smart future?[J]. Biomaterials, 2007, 28(34): 5185-5192. DOI: 10.1016/j.biomaterials.2007.07.044.
23.	Wang K, Han Z. Injectable hydrogels for ophthalmic applications[J]. J Control Release, 2017, 268: 212-224. DOI: 10.1016/j.jconrel.2017.10.031.
24.	Naik K, du Toit LC, Ally N, et al. In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye[J]. Drug Deliv Transl Res, 2024, 14(10): 2668-2694. DOI: 10.1007/s13346-024-01566-1.
25.	Patel DK, Jung E, Priya S, et al. Recent advances in biopolymer-based hydrogels and their potential biomedical applications[J/OL]. Carbohydr Polym, 2024, 323: 121408[2024-01-01]. https://pubmed.ncbi.nlm.nih.gov/37940291/. DOI: 10.1016/j.carbpol.2023.121408.
26.	Schnichels S, Schneider N, Hohenadl C, et al. Efficacy of two different thiol-modified crosslinked hyaluronate formulations as vitreous replacement compared to silicone oil in a model of retinal detachment[J/OL]. PLoS One, 2017, 12(3): e0172895[2017-03-01]. https://pubmed.ncbi.nlm.nih.gov/28248989/. DOI: 10.1371/journal.pone.0172895.
27.	Baino F. Towards an ideal biomaterial for vitreous replacement: Historical overview and future trends[J]. Acta Biomater, 2011, 7(3): 921-935. DOI: 10.1016/j.actbio.2010.10.030.
28.	Liang C, Peyman GA, Serracarbassa P, et al. An evaluation of methylated collagen as a substitute for vitreous and aqueous humor[J]. Int Ophthalmol, 1998, 22(1): 13-18. DOI: 10.1023/a:1006016809070.
29.	Nakagawa M, Tanaka M, Miyata T. Evaluation of collagen gel and hyaluronic acid as vitreous substitutes[J]. Ophthalmic Res, 1997, 29(6): 409-420. DOI: 10.1159/000268042.
30.	Su WY, Chen KH, Chen YC, et al. An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute[J]. J Biomater Sci Polym Ed, 2011, 22(13): 1777-1797. DOI: 10.1163/092050610x522729.
31.	Lang L, Hao H, Yao J, et al. Purely zwitterionic polymer injectable hydrogels for vitreous substitutes[J]. Science China Materials, 2025, 68(9): 3390-3400. DOI: 10.1007/s40843-025-3620-x.
32.	Hayashi K, Okamoto F, Hoshi S, et al. Fast-forming hydrogel with ultralow polymeric content as an artificial vitreous body[J]. Nat Biomed Eng, 2017, 1(3): 44. DOI: 10.1038/s41551-017-0044.
33.	Hurst J, Rickmann A, Heider N, et al. Long-term biocompatibility of a highly viscously thiol-modified cross-linked hyaluronate as a novel vitreous body substitute[J/OL]. Front Pharmacol, 2022, 13: 817353[2022-03-02]. https://pubmed.ncbi.nlm.nih.gov/35308238/. DOI: 10.3389/fphar.2022.817353.
34.	Baker AEG, Cui H, Ballios BG, et al. Stable oxime-crosslinked hyaluronan-based hydrogel as a biomimetic vitreous substitute[J/OL]. Biomaterials, 2021, 271: 120750[2021-04-04]. https://pubmed.ncbi.nlm.nih.gov/33725584/. DOI: 10.1016/j.biomaterials.2021.120750.
35.	Yu S, Wang S, Xia L, et al. Injectable self-crosslinking hydrogels based on hyaluronic acid as vitreous substitutes[J]. Int J Biol Macromol, 2022, 208: 159-171. DOI: 10.1016/j.ijbiomac.2022.03.046.
36.	Ran R, Shi W, Gao Y, et al. Super-fast in situ formation of hydrogels based on multi-arm functional polyethylene glycols as endotamponade substitutes[J]. J Mater Chem B, 2021, 9(44): 9162-9173. DOI: 10.1039/d1tb01825f.
37.	He B, Yang J, Liu Y, et al. An in situ-forming polyzwitterion hydrogel: towards vitreous substitute application[J]. Bioact Mater, 2021, 6(10): 3085-3096. DOI: 10.1016/j.bioactmat.2021.02.029.
38.	Cai Y, Tan Y, Cao J, et al. Dual-crosslinked betaine-based amphiphilic hydrogel as a promising vitreous substitute: anti-adhesion, anti-fouling, and anti-cell proliferation[J/OL]. Adv Sci (Weinh), 2025: e13455[2025-06-30]. https://pubmed.ncbi.nlm.nih.gov/40586226/. DOI: 10.1002/advs.202413455.
39.	Wang S, Ong P J, Liu S, et al. Recent advances in host-guest supramolecular hydrogels for biomedical applications[J/OL]. Chem Asian J, 2022, 17(18): e202200608[2022-09-14]. https://pubmed.ncbi.nlm.nih.gov/35866560/. DOI: 10.1002/asia.202200608.
40.	Xue K, Liu Z, Jiang L, et al. A new highly transparent injectable PHA-based thermogelling vitreous substitute[J]. Biomater Sci, 2020, 8(3): 926-936. DOI: 10.1039/c9bm01603a.
41.	Schulz A, Keskar M, Swindle-Reilly KE, et al. Replacing the vitreous body with hydrogels: rationale and strategies[J/OL]. Prog Retin Eye Res, 2025, 108: 101389[2025-07-09]. https://pubmed.ncbi.nlm.nih.gov/40645475/. DOI: 10.1016/j.preteyeres.2025.101389.
42.	Jin Y, Li Y, Song S, et al. DNA supramolecular hydrogel as a biocompatible artificial vitreous substitute[J]. Adv Mater Interfaces, 2021, 9(5): .1-9. DOI: 10.1002/admi.202101321.
43.	Cai Y, Xiang Y, Dong H, et al. Injectable self-assembling peptide hydrogel as a promising vitreous substitute[J]. J Control Release, 2024, 376: 402-412. DOI: 10.1016/j.jconrel.2024.10.016.
44.	Choi G, An SH, Choi J W, et al. Injectable alginate-based in situ self-healable transparent hydrogel as a vitreous substitute with a tamponading function[J/OL]. Biomaterials, 2024, 305: 122459[2024-01-01]. https://pubmed.ncbi.nlm.nih.gov/38199216/. DOI: 10.1016/j.biomaterials.2023.122459.
45.	Schulz A, Boneva SK, Lange C, et al. Tissue engineering of the vitreous body: recent progress and future trends[J]. Curr Opin Ophthalmol, 2025, 36(3): 262-269. DOI: 10.1097/icu.0000000000001125.
46.	Yadav I, Purohit SD, Singh H, et al. Meropenem loaded 4-arm-polyethylene-succinimidyl-carboxymethyl ester and hyaluronic acid based bacterial resistant hydrogel[J/OL]. Int J Biol Macromol, 2023, 235: 123842[2023-04-30]. https://pubmed.ncbi.nlm.nih.gov/36854369/. DOI: 10.1016/j.ijbiomac.2023.123842.
47.	Chen HA, Tai YN, Hsieh EH, et al. Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes[J/OL]. Int J Biol Macromol, 2024, 275(Pt1): 133467[2024-06-28]. https://pubmed.ncbi.nlm.nih.gov/38945319/. DOI: 10.1016/j.ijbiomac.2024.133467.
48.	Naik K, du Toit LC, Ally N, et al. In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye[J]. Drug Deliv Transl Res, 2024, 14(10): 2668-2694. DOI: 10.1007/s13346-024-01566-1.

1. Monteiro JP, Santos FM, Rocha AS, et al. Vitreous humor in the pathologic scope: insights from proteomic approaches[J]. Proteomics Clin Appl, 2015, 9(1-2): 187-202. DOI: 10.1002/prca.201400133.
2. Scott JE. The chemical morphology of the vitreous[J]. Eye (Lond), 1992, 6(Pt 6): 553-555. DOI: 10.1038/eye.1992.120.
3. Singh A, Boulton M, Lane C, et al. Inhibition of microvascular endothelial cell proliferation by vitreous following retinal scatter photocoagulation[J]. Br J Ophthalmol, 1990, 74(6): 328-332. DOI: 10.1136/bjo.74.6.328.
4. Purtskhvanidze K, Hillenkamp J, Tode J, et al. Thinning of inner retinal layers after vitrectomy with silicone oil versus gas endotamponade in eyes with macula-off retinal detachment[J]. Ophthalmologica, 2017, 238(3): 124-132. DOI: 10.1159/000477743.
5. Feng X, Li C, Zheng Q, et al. Risk of silicone oil as vitreous tamponade in pars plana vitrectomy: a systematic review and meta-analysis[J]. Retina, 2017, 37(11): 1989-2000. DOI: 10.1097/iae.0000000000001553.
6. Haave H, Petrovski B, Zaj?c M, et al. Outcomes from the retrospective multicenter cross-sectional study on lamellar macular hole surgery[J]. Clin Ophthalmol, 2022, 16: 1847-1860. DOI: 10.2147/opth.S351932.
7. Liu Z, Liow SS, Lai SL, et al. Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade[J]. Nat Biomed Eng, 2019, 3(8): 598-610. DOI: 10.1038/s41551-019-0382-7.
8. Singh SR, Dhurandhar D, Chhablani J. Sandwich technique using a combination of perfluoropropane and silicone oil for inferior retinal detachment[J]. Indian J Ophthalmol, 2018, 66(7): 988-990. DOI: 10.4103/ijo.IJO_1294_17.
9. Gao QY, Fu Y, Hui YN. Vitreous substitutes: challenges and directions[J]. Int J Ophthalmol, 2015, 8(3): 437-440. DOI: 10.3980/j.issn.2222-3959.2015.03.01.
10. Gozawa M, Kanamoto M, Ishida S, et al. Evaluation of intraocular gas using magnetic resonance imaging after pars plana vitrectomy with gas tamponade for rhegmatogenous retinal detachment[J/OL]. Sci Rep, 2020, 10(1): 1521[2020-01-30]. https://pubmed.ncbi.nlm.nih.gov/32001793/. DOI: 10.1038/s41598-020-58508-3.
11. Kim SS, Smiddy WE, Feuer WJ, et al. Outcomes of sulfur hexafluoride (SF6) versus perfluoropropane (C3F8) gas tamponade for macular hole surgery[J]. Retina, 2008, 28(10): 1408-1415. DOI: 10.1097/IAE.0b013e3181885009.
12. Giansanti F, Tartaro R, Caporossi T, et al. An internal limiting membrane plug and gas endotamponade for recurrent or persistent macular holeJ/OL]. J Ophthalmol, 2019, 2019: 6051724[2019-04-07]. https://pubmed.ncbi.nlm.nih.gov/30956814/. DOI: 10.1155/2019/6051724.
13. Su X, Tan MJ, Li Z, et al. Recent progress in using biomaterials as vitreous substitutes[J]. Biomacromolecules, 2015, 16(10): 3093-3102. DOI: 10.1021/acs.biomac.5b01091.
14. Yadav I, Purohit SD, Singh H, et al. Vitreous substitutes: an overview of the properties, importance, and development[J]. J Biomed Mater Res B Appl Biomater, 2021, 109(8): 1156-1176. DOI: 10.1002/jbm.b.34778.
15. Marti M, Walton R, B?ni C, et al. Increased intraocular pressure is a risk factor for unexplained visual loss during silicone oil endotamponade[J]. Retina, 2017, 37(12): 2334-2340. DOI: 10.1097/iae.0000000000001492.
16. Davo-Cabrera JM, Lanzagorta-Aresti A, Alcocer Yuste P. A novel surgical technique for ahmed valves in refractory glaucoma with silicone oil endotamponade[J/OL]. J Glaucoma, 2017, 26(10): e232-e235[2017-10-01]. https://pubmed.ncbi.nlm.nih.gov/28816817/. DOI: 10.1097/ijg.0000000000000737.
17. Valentín-Bravo FJ, García-Onrubia L, Andrés-Iglesias C, et al. Complications associated with the use of silicone oil in vitreoretinal surgery: a systemic review and meta-analysis[J/OL]. Acta Ophthalmol, 2022, 100(4): e864-e880[2021-11-29]. https://pubmed.ncbi.nlm.nih.gov/34846097/. DOI: 10.1111/aos.15055.
18. Naik K, Du Toit LC, Ally N, et al. Advances in polysaccharide- and synthetic polymer-based vitreous substitutes[J/OL]. Pharmaceutics, 2023, 15(2): 566[2023-02-08]. https://pubmed.ncbi.nlm.nih.gov/36839888/. DOI: 10.3390/pharmaceutics15020566.
19. Tobalem SJ, Weinberger A, Kropp M, et al. Chorioretinal toxicity of perfluorooctane (Ala OCTA): results from 48 surgical procedures in geneva[J]. Am J Ophthalmol, 2020, 218: 28-39. DOI: 10.1016/j.ajo.2020.05.014.
20. Januschowski K, Irigoyen C, Pastor JC, et al. Retinal toxicity of medical devices used during vitreoretinal surgery: a critical overview[J]. Ophthalmologica, 2018, 240(4): 236-243. DOI: 10.1159/000488504.
21. Qu S, Tang Y, Ning Z, et al. Desired properties of polymeric hydrogel vitreous substitute[J/OL]. Biomed Pharmacother, 2024, 172: 116154[2024-02-01]. https://pubmed.ncbi.nlm.nih.gov/38306844/. DOI: 10.1016/j.biopha.2024.116154.
22. Kopecek J. Hydrogel biomaterials: a smart future?[J]. Biomaterials, 2007, 28(34): 5185-5192. DOI: 10.1016/j.biomaterials.2007.07.044.
23. Wang K, Han Z. Injectable hydrogels for ophthalmic applications[J]. J Control Release, 2017, 268: 212-224. DOI: 10.1016/j.jconrel.2017.10.031.
24. Naik K, du Toit LC, Ally N, et al. In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye[J]. Drug Deliv Transl Res, 2024, 14(10): 2668-2694. DOI: 10.1007/s13346-024-01566-1.
25. Patel DK, Jung E, Priya S, et al. Recent advances in biopolymer-based hydrogels and their potential biomedical applications[J/OL]. Carbohydr Polym, 2024, 323: 121408[2024-01-01]. https://pubmed.ncbi.nlm.nih.gov/37940291/. DOI: 10.1016/j.carbpol.2023.121408.
26. Schnichels S, Schneider N, Hohenadl C, et al. Efficacy of two different thiol-modified crosslinked hyaluronate formulations as vitreous replacement compared to silicone oil in a model of retinal detachment[J/OL]. PLoS One, 2017, 12(3): e0172895[2017-03-01]. https://pubmed.ncbi.nlm.nih.gov/28248989/. DOI: 10.1371/journal.pone.0172895.
27. Baino F. Towards an ideal biomaterial for vitreous replacement: Historical overview and future trends[J]. Acta Biomater, 2011, 7(3): 921-935. DOI: 10.1016/j.actbio.2010.10.030.
28. Liang C, Peyman GA, Serracarbassa P, et al. An evaluation of methylated collagen as a substitute for vitreous and aqueous humor[J]. Int Ophthalmol, 1998, 22(1): 13-18. DOI: 10.1023/a:1006016809070.
29. Nakagawa M, Tanaka M, Miyata T. Evaluation of collagen gel and hyaluronic acid as vitreous substitutes[J]. Ophthalmic Res, 1997, 29(6): 409-420. DOI: 10.1159/000268042.
30. Su WY, Chen KH, Chen YC, et al. An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute[J]. J Biomater Sci Polym Ed, 2011, 22(13): 1777-1797. DOI: 10.1163/092050610x522729.
31. Lang L, Hao H, Yao J, et al. Purely zwitterionic polymer injectable hydrogels for vitreous substitutes[J]. Science China Materials, 2025, 68(9): 3390-3400. DOI: 10.1007/s40843-025-3620-x.
32. Hayashi K, Okamoto F, Hoshi S, et al. Fast-forming hydrogel with ultralow polymeric content as an artificial vitreous body[J]. Nat Biomed Eng, 2017, 1(3): 44. DOI: 10.1038/s41551-017-0044.
33. Hurst J, Rickmann A, Heider N, et al. Long-term biocompatibility of a highly viscously thiol-modified cross-linked hyaluronate as a novel vitreous body substitute[J/OL]. Front Pharmacol, 2022, 13: 817353[2022-03-02]. https://pubmed.ncbi.nlm.nih.gov/35308238/. DOI: 10.3389/fphar.2022.817353.
34. Baker AEG, Cui H, Ballios BG, et al. Stable oxime-crosslinked hyaluronan-based hydrogel as a biomimetic vitreous substitute[J/OL]. Biomaterials, 2021, 271: 120750[2021-04-04]. https://pubmed.ncbi.nlm.nih.gov/33725584/. DOI: 10.1016/j.biomaterials.2021.120750.
35. Yu S, Wang S, Xia L, et al. Injectable self-crosslinking hydrogels based on hyaluronic acid as vitreous substitutes[J]. Int J Biol Macromol, 2022, 208: 159-171. DOI: 10.1016/j.ijbiomac.2022.03.046.
36. Ran R, Shi W, Gao Y, et al. Super-fast in situ formation of hydrogels based on multi-arm functional polyethylene glycols as endotamponade substitutes[J]. J Mater Chem B, 2021, 9(44): 9162-9173. DOI: 10.1039/d1tb01825f.
37. He B, Yang J, Liu Y, et al. An in situ-forming polyzwitterion hydrogel: towards vitreous substitute application[J]. Bioact Mater, 2021, 6(10): 3085-3096. DOI: 10.1016/j.bioactmat.2021.02.029.
38. Cai Y, Tan Y, Cao J, et al. Dual-crosslinked betaine-based amphiphilic hydrogel as a promising vitreous substitute: anti-adhesion, anti-fouling, and anti-cell proliferation[J/OL]. Adv Sci (Weinh), 2025: e13455[2025-06-30]. https://pubmed.ncbi.nlm.nih.gov/40586226/. DOI: 10.1002/advs.202413455.
39. Wang S, Ong P J, Liu S, et al. Recent advances in host-guest supramolecular hydrogels for biomedical applications[J/OL]. Chem Asian J, 2022, 17(18): e202200608[2022-09-14]. https://pubmed.ncbi.nlm.nih.gov/35866560/. DOI: 10.1002/asia.202200608.
40. Xue K, Liu Z, Jiang L, et al. A new highly transparent injectable PHA-based thermogelling vitreous substitute[J]. Biomater Sci, 2020, 8(3): 926-936. DOI: 10.1039/c9bm01603a.
41. Schulz A, Keskar M, Swindle-Reilly KE, et al. Replacing the vitreous body with hydrogels: rationale and strategies[J/OL]. Prog Retin Eye Res, 2025, 108: 101389[2025-07-09]. https://pubmed.ncbi.nlm.nih.gov/40645475/. DOI: 10.1016/j.preteyeres.2025.101389.
42. Jin Y, Li Y, Song S, et al. DNA supramolecular hydrogel as a biocompatible artificial vitreous substitute[J]. Adv Mater Interfaces, 2021, 9(5): .1-9. DOI: 10.1002/admi.202101321.
43. Cai Y, Xiang Y, Dong H, et al. Injectable self-assembling peptide hydrogel as a promising vitreous substitute[J]. J Control Release, 2024, 376: 402-412. DOI: 10.1016/j.jconrel.2024.10.016.
44. Choi G, An SH, Choi J W, et al. Injectable alginate-based in situ self-healable transparent hydrogel as a vitreous substitute with a tamponading function[J/OL]. Biomaterials, 2024, 305: 122459[2024-01-01]. https://pubmed.ncbi.nlm.nih.gov/38199216/. DOI: 10.1016/j.biomaterials.2023.122459.
45. Schulz A, Boneva SK, Lange C, et al. Tissue engineering of the vitreous body: recent progress and future trends[J]. Curr Opin Ophthalmol, 2025, 36(3): 262-269. DOI: 10.1097/icu.0000000000001125.
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Latest ArticlesResearch progress of in situ crosslinked hydrogels as vitreous substitutes

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