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仿生热敏水凝胶作为玻璃体替代物:合成、性质及动物研究进展

Bioinspired Thermosensitive Hydrogel as a Vitreous Substitute: Synthesis, Properties, and Progress of Animal Studies.

作者信息

Laradji Amine, Shui Ying-Bo, Karakocak Bedia Begum, Evans Lynn, Hamilton Paul, Ravi Nathan

机构信息

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

Department of Veterans Affairs, St. Louis Medical Center, St. Louis, MO 63106, USA.

出版信息

Materials (Basel). 2020 Mar 15;13(6):1337. doi: 10.3390/ma13061337.

DOI:10.3390/ma13061337
PMID:32183465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7143394/
Abstract

In many vitreal diseases, the surgeon removes the natural vitreous and replaces it with silicone oils, gases, or balanced salt solutions to fill the eyeball and hold the retina in position. However, these materials are often associated with complications and have properties that differ from natural vitreous. Herein, we report an extension of our previous work on the synthesis of a biomimetic hydrogel that is composed of thiolated gellan as an analogue of type II collagen and poly(methacrylamide-co-methacrylate-co-bis(methacryloyl)cystamine), a polyelectrolyte, as an analogue of hyaluronic acid. This thermosensitive hydrogel can be injected into the eye as a viscous solution at 45 °C. It then forms a physical gel in situ when it reaches body temperature, and later forms disulfide covalent crosslinks. In this article, we evaluated two different formulations of the biomimetic hydrogels for their physical, mechanical, and optical properties, and we determined their biocompatibility with several cell lines. Finally, we report on the progress of the four-month preclinical evaluation of our bio-inspired vitreous substitute in comparison to silicone oil or a balanced salt solution. We assessed the eyes with a slit-lamp examination, intraocular pressure measurements, electroretinography, and optical coherence tomography. Preliminary results are very encouraging for the continuing evaluation of our bio-inspired hydrogel in clinical trials.

摘要

在许多玻璃体疾病中,外科医生会去除天然玻璃体,并用硅油、气体或平衡盐溶液替代,以填充眼球并使视网膜保持在原位。然而,这些材料常常伴有并发症,且其特性与天然玻璃体不同。在此,我们报告了之前关于合成一种仿生水凝胶工作的拓展,该水凝胶由作为II型胶原蛋白类似物的硫醇化结冷胶和作为透明质酸类似物的聚(甲基丙烯酰胺 - 甲基丙烯酸酯 - 双(甲基丙烯酰)胱胺)(一种聚电解质)组成。这种热敏性水凝胶在45℃时可作为粘性溶液注入眼内。当它达到体温时,会原位形成物理凝胶,随后形成二硫键共价交联。在本文中,我们评估了两种不同配方的仿生水凝胶的物理、机械和光学性质,并确定了它们与几种细胞系的生物相容性。最后,我们报告了与硅油或平衡盐溶液相比,我们的仿生玻璃体替代物进行的为期四个月的临床前评估进展情况。我们通过裂隙灯检查、眼压测量、视网膜电图和光学相干断层扫描对眼睛进行了评估。初步结果对于在临床试验中继续评估我们的仿生水凝胶非常令人鼓舞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/03faad89ea3c/materials-13-01337-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/0c67841ab719/materials-13-01337-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/d4e893a504bd/materials-13-01337-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/a2609fc06a94/materials-13-01337-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/a9cb4aa689c7/materials-13-01337-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/03faad89ea3c/materials-13-01337-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/0c67841ab719/materials-13-01337-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/d36b6dcd3a21/materials-13-01337-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/6d38e2a51211/materials-13-01337-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/78ac77bf77d6/materials-13-01337-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/d4e893a504bd/materials-13-01337-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/a2609fc06a94/materials-13-01337-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/a9cb4aa689c7/materials-13-01337-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d8/7143394/03faad89ea3c/materials-13-01337-g008.jpg

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