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Reduction of Intracochlear Trauma and Fibrosis Using Dual Network, Zwitterionic Hydrogel Thin Films on Cochlear Implant Surfaces

使用人工耳蜗表面上的双网络两性离子水凝胶薄膜减少耳蜗内创伤和纤维化

基本信息

批准号：
10659699
负责人：
Allan Guymon
金额：
$ 56.01万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-04 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659699
关键词：
3-Dimensional Acoustic Nerve Acoustics Adhesions Auditory Bacteria Bacterial Adhesion Biocompatible Materials Biological Cadaver Cell Adhesion Cells Chemicals Cicatrix Clinical Cochlea Cochlear Implants Complex Data Development Devices Dexamethasone Drug Delivery Systems Effectiveness Electric Stimulation Electrophysiology (science)Engineering Equilibrium Fibrosis Film Foreign Bodies Fracture Friction Funding Glucocorticoids Glycolates Health Hearing Histologic Housing Human Hydrogels Implant Implanted Electrodes Inflammation Inflammatory Kinetics Legal patent Masks Measures Mechanics Medical Device Membrane Proteins Methods Microspheres Modeling Modulus Mus Music Patients Performance Platinum Polymers Process Property Proteins Reaction Reporter Residual state Resistance Resolution Safety Signal Transduction Silastic Staphylococcus aureus Structure Surface Surface Properties System Technology Testing Thick Thinness Tissues Transducers Translations Trauma Water Work X ray microscopy capsule combat crosslink deaf density electric impedance flexibility functional improvement hearing impairment hearing restoration implant coating implant material implantation improved learning materials mechanical properties medical implant mouse model neuroprosthesis new technology novel novel therapeutics polycaprolactone polymerization pre-clinical preservation prevent radiological imaging response sheep model speech in noise surface coating

项目摘要

Project Summary Cochlear implant (CI) electrode arrays are made of platinum wires and contacts encased in a silastic housing. These materials provide mechanical stability and flexibility critical to the long-term function of the CI. However, they also induce local tissue reactions that can have detrimental effects. For example, trauma from insertion of the CI can damage cochlear health and any residual acoustic hearing. Further, the fibrotic capsule that encases CI electrode arrays leads to increased impedances and decreased signal resolution which reduce CI effectiveness. Intracochlear fibrosis is also implicated in the loss of acoustic hearing that can occur months to years after implantation. Thus, developing materials that mitigate insertion trauma and the inflammatory, fibrous response to CI materials could significantly improve device function and safety. Ultra-low fouling zwitterionic polymers are a new class of materials that show significant promise to eliminate fibrosis. However as bulk materials they lack mechanical properties and long term durability suitable for use in CIs. To leverage the ultra-low fouling surface properties of zwitterionic polymers while maintaining the proven mechanical properties of current CI materials, we recently established a novel, patented photochemical process for simultaneous polymerization, grafting and cross-linking of zwitterionic thin films on relevant CI materials. We now leverage the mechanical advantages of recently developed dual network polymer technology to enhance the strength of the thin films. We also use the thin films as novel drug delivery platforms with controlled and sustained kinetics. We hypothesize that robust dual network, zwitterionic thin film coatings will maintain long- term anti-fouling properties; reduce friction, insertion trauma, and intracochlear fibrosis; and provide controlled sustained release of glucocorticoids. Accordingly, in Aim 1 we engineer robust, dual network zwitterionic thin films for ultra-low fouling CI biomaterial coatings. Aim 2 investigates the effect of dual network, zwitterionic thin film hydrogel CI coatings on tissue friction, insertion forces, cochlear trauma, and fibrosis using human cadaver and sheep models. Finally, Aim 3 develops zwitterionic thin film hydrogel coatings with controllable, sustained glucocorticoid delivery systems to reduce intracochlear inflammation and fibrosis in reporter mouse CI models. Development of robust zwitterionic thin film coatings on implanted biomaterials that are lubricious, ultra-low fouling, and capable of controlled and sustained drug delivery represents a transformative advance to prevent trauma, reduce fibrosis, and improve the functional outcomes associated with placement of medical devices, such as CIs, in the body.

项目摘要人工耳蜗(CI)电极阵列由包裹在硅橡胶外壳中的铂丝和触点制成。这些材料提供了机械稳定性和灵活性，对CI的长期功能至关重要。然而，它们还会引发局部组织反应，从而产生有害影响。例如，置入的创伤 CI会损害耳蜗健康和任何残留的声学听力。此外，纤维性胶囊封闭CI电极阵列会导致阻抗增加和信号分辨率降低，从而降低CI 有效性。脉络膜内纤维化也与听力丧失有关，这种听力损失可以发生在几个月到植入数年后。因此，开发能够减轻插入创伤和炎症的材料，对CI材料的纤维性反应可显著改善装置的功能和安全性。超低污垢两性离子聚合物是一种新型材料，显示出消除纤维化的重大前景。然而，作为块状材料，它们缺乏适用于独联体的力学性能和长期耐久性。以杠杆作用两性离子聚合物的超低污垢表面性能，同时保持已证实的机械性能为了研究现有CI材料的性能，我们最近建立了一种新的、获得专利的光化学工艺，用于两性离子薄膜在相关CI材料上的同时聚合、接枝和交联。我们现在利用最近开发的双网络聚合物技术的机械优势来增强薄膜的强度。我们还将薄膜用作新型药物输送平台，具有受控和持续的动力学。我们假设，坚固的双网络、两性离子薄膜涂层将长期保持在术语防污染性能；减少摩擦、插入创伤和脉络膜内纤维化；并提供受控糖皮质激素的持续释放。因此，在目标1中，我们设计了健壮的双网络两性离子薄膜用于超低污垢CI生物材料涂料的薄膜。目的2研究双网络两性离子薄膜的作用膜水凝胶CI涂层对人体身体组织摩擦、插入力、耳蜗伤和纤维化的影响还有绵羊模特。最后，目标3开发了可控、可持续的两性离子薄膜水凝胶涂层。糖皮质激素给药系统减少报告小鼠脑梗塞模型中的脑白质炎症和纤维化。植入型超低润滑生物材料上强韧两性离子薄膜涂层的研制污染，并能够控制和持续的药物输送是一项变革性的进步，以防止创伤，减少纤维化，并改善与医疗器械放置相关的功能结果，例如顺式，在身体里。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intracellular calcium and cyclic nucleotide levels modulate neurite guidance by microtopographical substrate features.

细胞内钙和环状核苷酸水平通过微观形态底物特征调节神经突引导。

DOI：
10.1002/jbm.a.35738
发表时间：
2016-08
期刊：
Journal of biomedical materials research. Part A
影响因子：
0
作者：
Li S;Tuft B;Xu L;Polacco M;Clarke JC;Guymon CA;Hansen MR
通讯作者：
Hansen MR

Zwitterionic Photografted Coatings of Cochlear Implant Biomaterials Reduce Friction and Insertion Forces.

DOI：
10.1097/mao.0000000000003288
发表时间：
2021-12-01
期刊：
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
影响因子：
0
作者：
Bennion DM;Horne R;Peel A;Reineke P;Henslee A;Kaufmann C;Guymon CA;Hansen MR
通讯作者：
Hansen MR

Photopolymerized micropatterns with high feature frequencies overcome chemorepulsive borders to direct neurite growth.

具有高特征频率的光聚合微图案克服了化学脉冲边界以引导神经突生长。

DOI：
10.1002/term.2527
发表时间：
2018
期刊：
Journal of tissue engineering and regenerative medicine
影响因子：
3.3
作者：
Tuft,BradleyW;Xu,Linjing;Leigh,Braden;Lee,Daniel;Guymon,CAllan;Hansen,MarlanR
通讯作者：
Hansen,MarlanR

Material stiffness effects on neurite alignment to photopolymerized micropatterns.

DOI：
10.1021/bm501019s
发表时间：
2014-10-13
期刊：
BIOMACROMOLECULES
影响因子：
6.2
作者：
Tuft, Bradley W.;Zhang, Lichun;Xu, Linjing;Hangartner, Austin;Leigh, Braden;Hansen, Marlan R.;Guymon, C. Allan
通讯作者：
Guymon, C. Allan

Neural pathfinding on uni- and multidirectional photopolymerized micropatterns.

DOI：
10.1021/am501622a
发表时间：
2014-07-23
期刊：
ACS APPLIED MATERIALS & INTERFACES
影响因子：
9.5
作者：
Tuft, Bradley W.;Xu, Linjing;White, Scott P.;Seline, Alison E.;Erwood, Andrew M.;Hansen, Marian R.;Guymon, C. Allan
通讯作者：
Guymon, C. Allan