Preparation, characterization and application research of a sustained dexamethasone releasing electrode coating for cochlear implantation
Preparation, characterization and application research of a sustained dexamethasone releasing electrode coating for cochlear implantation
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人工耳蜗植入用地塞米松缓释电极涂层的制备、表征及应用研究
DOI：
10.1016/j.msec.2018.04.033
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发表时间：
2018-09-01
影响因子：
7.9
通讯作者：
Zhang, Hongzheng
中科院分区：
文献类型：
--
作者：
Xu, Muqing;Ma, Dong;Zhang, Hongzheng
人工耳蜗植入术后耳蜗炎性反应是导致植入损伤和听力损失的重要机制。听力损失也是由听觉毛细胞（HC）的损伤引起的，而耳蜗内的离子稳态可以确保HC的存活。本文以透明质酸（HA）为原料，采用1，4-丁二醇二缩水甘油醚（BDDE）交联HA，通过流变学和红外光谱分析证实了交联HA的成功制备。制备人工外淋巴液（APL）模拟人耳蜗鼓阶内离子稳态微环境，并作为人工外淋巴液浸泡CHA（APL-CHA）的主要成分。电导率实验表明，APL-CHA更符合鼓阶电导率的要求。通过对电极涂敷工艺的研究发现，与普通涂敷方法相比，挤压涂敷法具有APL-CHA粘附能力可控、涂层厚度均匀、表面光滑等优点。由于CI手术应用要求，涂层工艺的优化选择如下：挤出涂层方法，度为3.6体积%，针孔直径为32 G（110 gm），压力为200 +/- 15.81 Psi。通过经验证的HPLC方法，使用水凝胶填充的储药器可以证明地塞米松21-磷酸钠盐（DSP）的受控释放为20天。CHA的形态结构显示APL-CHA之间存在大小不一的多孔结构，为药物释放提供了结构基础。L929成纤维细胞培养和螺旋神经节神经元培养结果表明，APL-CHA具有良好的生物相容性。APL-CHA在CI手术中显示出有希望的应用，并且在预防听力损失方面具有很大的潜力，其具有良好的耳蜗内离子稳态模拟、用于靶向抗炎的局部DSP递送、鼓阶内的近似导电性以及电极涂覆工艺的优化。
Cochlear inflammatory response after cochlear implantation (CI) is an important mechanism for implantation trauma and hearing loss. The hearing loss was also caused by damage to auditory hair cells (HCs), whereas ion homeostasis within the cochlea can ensure survival of HCs. In our study, pure hyaluronic acid (HA) was crosslinked with 1, 4-butanediol diglycidyl ether (BDDE) and the successful preparation of the cross-linked hydrogel (CHA) was confirmed by rheological characteristics and FTIR spectra. Artificial perilymph (APL) was prepared to simulate the ion homeostasis microenvironment within scala tympani of human cochlear, and served as the major component of artificial perilymph soaked CHA (APL-CHA). The conductivity experiment indicated that APL-CHA is more suitable to the requirements of the electrical conductivity in scala tympani. The electrode coating process found that the extrusion coating method have advantages of controllable adhesive capacity of APL-CHA, uniform coating thickness and smooth surface as compared to common method. Due to CI surgery application requirement, optimization of coating process was selected as follows: extrusion coating method, degree of 3.6 vol%, pinhole diameter of 32G (110 gm), pressure of 200 +/- 15.81 Psi. Controlled dexamethasone 21-phosphate sodium salt (DSP) release of 20 days could be demonstrated using the hydrogel filled reservoir via a validated HPLC method. The morphological structure of CHA showed different sizes of porous structure among APL-CHA provided structural basis for drug delivery. L929 fibroblasts culture and Spiral Ganglion Neuron Explants culture results revealed that APL-CHA possesses fine biological compatibility. APL-CHA shows a promising application in CI surgery and has great potential in preventing hearing loss with well simulation of ion homeostasis within the cochlear, local DSP delivery for target anti-inflammatory, approximate conductivity within the scala tympani and optimization of electrode coating process.