Biocompatible retinal prosthesis based on a conjugated polymer photoactive layer

 描述（由申请人提供）：本提案是为了响应NEI在附录A中定义的特定批准主题领域：美国国立卫生研究院SBA批准的SBIR/STTR主题，用于从PHS 2014-2 SBIR/STTR拨款申请的综合征集中获得超过法定预算限制的奖项。该I期可行性研究是一项先进的技术项目，具有明确识别的产品，将导致视网膜疾病的临床相关治疗。授标期和申请的金额以项目需求为指导，并符合已发布的准则。视网膜变性和视网膜色素变性是导致数百万人失明的原因。治疗选择，如移植，维生素补充剂或药物是可用的，但它们可能只用于减缓疾病或疗效有限。新的治疗选择，如基因或干细胞治疗，由于技术困难或安全性可疑，价值有限。假体选择是有希望的，正在进行临床评价。目前的假体模型有几个缺点，包括有限的分辨率，过多的外部硬件，以及生物相容性问题，部分原因是过热或电流产生。然而，共轭聚合物已被证明仅使用照明作为电源就能从视网膜中产生空间定位响应。与以前建立的视网膜假体相比，其优点包括很少或没有热量产生，生物相容性改善，并且不需要外部硬件或多电极阵列。为了更好的生物相容性和整体功能，我们建议开发更适合眼睛自身生物学的替代光敏材料。我们建议开发由涂覆有共轭聚合物嵌段共聚物的活性层的水凝胶基底组成的假体。这些材料是对目前用于视网膜激活的共轭聚合物研究的改进，因为它们是全软材料，能够使营养物质通过凝胶扩散。我们的具体目标是证明可行性，在体外生物相容性，稳定性和能力，激活视网膜神经元在视网膜变性大鼠视网膜。这些目标包括：1）共轭聚合物/水凝胶假体的配制，2）测定体外生物相容性和光化学稳定性，和3）用脱钙的光感受器退化大鼠视网膜离体证明假体操作。这些目标的成功完成将产生用于视网膜假体的合适候选物。我们将表征聚合物的光电化学活性和扩散营养物质的能力。我们还将通过评价在我们的材料上培养的细胞在光照下的活力和组织学来评估体外生物相容性和稳定性，因为它们将在操作中。我们将通过评估活动阈值、范围、频率和空间定位来评估它们刺激视网膜受损动物视网膜的能力。像这样的形状因素的修改可能会促使开发假肢技术的方法发生范式转变，并推动光激活神经接口的界限。

 DESCRIPTION (provided by applicant): This proposal is in response to a specific, approved topic area as defined by the NEI in Appendix A: National Institutes of Health SBA-Approved SBIR/STTR Topics for Awards over Statutory Budget Limitations from the PHS 2014-2 Omnibus Solicitation for SBIR/STTR Grant Applications. This Phase I feasibility study is an advanced technology project with a clearly identified product that will result in a clinically relevant treatment for retinal disease. The award period and amount requested are guided by project needs and are in compliance with issued guidelines. Age-related macular degeneration and retinitis pigmentosa are cause millions of cases of blindness due to retinal degradation. Treatment options such as transplants, vitamin supplements, or pharmaceuticals are available, but they may only serve to slow the disease or be of limited efficacy. New treatment options such as gene or stem cell therapy are of only limited value due to technical difficulties or questionable safety. Prosthetic options are promising and are undergoing clinical evaluation. There are several drawbacks with current prosthetic models including limited resolution, excessive external hardware, and biocompatibility problems in part due to excessive heat or current generation. Conjugated polymers, however, have been shown to produce a spatially localized response from explanted retinas using only illumination as a power source. The advantages over previously established retinal prosthetics include little to no heat generation, improved biocompatibility, and no need for external hardware or a multi-electrode array. For better biocompatibility and overall functionality, we propose the development of alternative photoactive materials that are better suited to the eye's own biology. We propose to develop prosthetics consisting of a hydrogel substrate coated with an active layer of conjugated polymer block copolymer. These materials are improvements upon the current research in conjugated polymers for retinal activation in that they are all-soft materials that enable the diffusion of nutrients through a gel. Our specific aims are designed to demonstrate feasibility, in vitro biocompatibility, stability, and ability to activate retinal neurons in explanted rat retinas. Thes aims include: 1) the formulation of conjugated polymer/hydrogel prostheses, 2) determine in vitro biocompatibility and photochemical stability, and 3) demonstrate prosthesis operation ex vivo with explanted photoreceptor degenerate rat retinas. Successful completion of these aims will yield suitable candidates to be used in a retinal prosthesis. We will characterize polymers fo their photoelectrochemical activity and ability to diffuse nutrients. We will also assess in vitro biocompatibility and stability by evaluating the viability and histology of cells cultured on our materials under illumination as they would be in operation. We will assess their ability to stimulate explanted animal retinas by evaluating activity threshold, range, frequency, and spatial localization. A revision of form factor such as this could precipitate a paradigm shift in the approach taken to develop prosthetic technologies as well as push boundaries in light-activated neural interfaces.