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具有机械响应性释放碱性成纤维细胞生长因子用于鼓膜修复的坚韧且自粘性两性离子水凝胶。

Tough and self-adhesive zwitterionic hydrogels with mechano-responsive release of bFGF for tympanic membrane repair.

作者信息

Chen Shengjia, Guo Xiangshu, Yang Yanyu, Deng Junjie, Xu Ting, Yuan Zhechen, Xue Hao, Niu Longxing, Wang Rong, Shen Yi

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, PR China.

Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, PR China.

出版信息

Mater Today Bio. 2024 Aug 24;28:101212. doi: 10.1016/j.mtbio.2024.101212. eCollection 2024 Oct.

Abstract

The tympanic membrane (TM) is constantly in a state of vibrating. However, there is currently a lack of drug-delivery scaffolds suitable for the dynamic environment of TM perforation. In this study, a mechano-responsive tough hydrogel was developed. It consists of basic fibroblast growth factor (bFGF)-loaded sodium alginate (SA) microspheres, polysulfobetaine methacrylate (polySBMA), and gelatin methacrylate (GelMA). This hydrogel was designed to serve as a TM scaffold to promote perforation healing under dynamic conditions. bFGF was encapsulated in SA microspheres, which were then incorporated into polySBMA-GelMA hydrogels through photo-initiated free radical polymerization. The mechanical properties, tissue adhesiveness, swelling properties, and degradation of the hydrogels were evaluated before and after microsphere incorporation. It was observed that incorporating bFGF-loaded SA microspheres did not significantly impact the adhesion and degradation mechanisms of the hydrogel. The compressive strength and tensile strength of the microsphere-incorporated hydrogel were up to 6.6 MPa and 64.1 kPa, respectively, suitable for a TM scaffold. The release behavior of bFGF from the hydrogel could be controlled by vibration stimulation without significantly affecting the hydrogel's mechanical properties, indicating a mechano-responsive nature of the hydrogel. The cytotoxicity assay demonstrated that the hydrogels showed no cytotoxic effects. Moreover, cell culture assays demonstrated that vibration stimulation could enhance the release of bFGF, significantly promoting cell proliferation and migration. The results demonstrate the significant potential of the mechano-responsive hydrogel as a scaffold for repairing TM perforations.

摘要

鼓膜(TM)始终处于振动状态。然而,目前缺乏适用于鼓膜穿孔动态环境的药物递送支架。在本研究中,开发了一种机械响应性坚韧水凝胶。它由负载碱性成纤维细胞生长因子(bFGF)的海藻酸钠(SA)微球、聚甲基丙烯酸磺酸甜菜碱(polySBMA)和甲基丙烯酸明胶(GelMA)组成。这种水凝胶被设计用作鼓膜支架,以促进动态条件下的穿孔愈合。bFGF被包裹在SA微球中,然后通过光引发自由基聚合将其掺入polySBMA-GelMA水凝胶中。在掺入微球前后评估了水凝胶的机械性能、组织粘附性、溶胀性能和降解情况。观察到掺入负载bFGF的SA微球对水凝胶的粘附和降解机制没有显著影响。掺入微球的水凝胶的抗压强度和抗拉强度分别高达6.6MPa和64.1kPa,适用于鼓膜支架。bFGF从水凝胶中的释放行为可以通过振动刺激来控制,而不会显著影响水凝胶的机械性能,表明水凝胶具有机械响应性。细胞毒性试验表明水凝胶没有细胞毒性作用。此外,细胞培养试验表明振动刺激可以增强bFGF的释放,显著促进细胞增殖和迁移。结果证明了机械响应性水凝胶作为修复鼓膜穿孔支架的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69bc/11647963/21156063cecc/ga1.jpg

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