SBIR Phase II: Design and Optimization of a Biocompatible Protein-Based Retinal Implant for the Treatment of End-Stage Retinal Degeneration

这项小型企业创新研究（SBIR）第二阶段项目的更广泛影响/商业潜力是开发和商业化一种高分辨率、基于蛋白质的视网膜植入物，旨在恢复数百万因视网膜退行性疾病（特别是视网膜色素变性和年龄相关性黄斑变性）而失明的患者的视力。这些目前无法治愈的致盲性疾病影响着全世界3000万至5000万人，并导致个人失去独立性，并增加了其护理人员的负担。虽然改善生活质量是这项技术最重要的成果，但降低治疗慢性视网膜变性的医疗成本和限制与医生的时间也将有利于广泛的医疗保健领域。 SBIR提案中概述的工作也有可能显著影响我们对视网膜退行性疾病的理解，这将有助于为许多眼科适应症开发更好，更有效的治疗方法。正在开发的视网膜下植入物为下一代高分辨率视网膜修复提供了框架，同时为视力恢复提供了具有成本效益的解决方案，并将帮助这些患者重新获得独立，从而提高他们的生活质量。拟议的项目将扩大从体内手术开发和离体疗效研究中收集的数据，这些研究由我们的I/IB期奖项支持。 首先，将进行一项40只动物的大鼠研究，以进一步研究视网膜植入物的生物相容性。 其次，先前开发的手术程序将在猪身上进行改进，以确保可重复和安全的视网膜下植入。第三，将设计高通量体外测定以研究许多植入物参数，以及使用视网膜色素上皮细胞的视网膜植入物的完整性和生物稳定性。 此外，将在本体外研究中研究医疗器械密封剂，并将使用时间分辨吸收光谱和离子敏感检测器测量植入物的功能完整性，该检测器专门为此应用开发。 最后，这种离子敏感检测器将提供进一步以高分辨率测量视网膜植入物的空间灵敏度的机会。 这些体内和体外研究对于持续评价植入物的生物相容性、手术可行性和有效性至关重要。 这些研究的结果将进一步证明正在开发的技术的商业可行性。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop and commercialize a high resolution, protein-based retinal implant intended to restore vision to the millions of patients blinded by retinal degenerative diseases, particularly retinitis pigmentosa and age-related macular degeneration. These currently incurable and blinding diseases affect between 30-50 million people worldwide, and lead to a loss of independence for the individual, as well as an increased burden on their caregivers. While improved quality of life is the most vital outcome of this technology, reduction of medical costs of treating chronic retinal degeneration and limiting time with doctors will also be of benefit to the broad healthcare field. The work outlined in this SBIR proposal also has the potential to significantly impact our understanding of retinal degenerative diseases, which will help in developing better and more effective treatments for a number of ophthalmic indications. The subretinal implant under development provides the framework for the next generation of high-resolution retinal prosthetics, while offering a cost-effective solution to vision restoration, and will help these patients regain independence and thus improve their quality of life. The proposed project will expand on the data collected from the in vivo surgical development and ex vivo efficacy studies supported by our Phase I/IB awards. First, a 40-animal rat study will be undertaken to further investigate the biocompatibility of the retinal implant. Second, previously developed surgical procedures will be refined in pigs to ensure reproducible and safe subretinal implantation. Third, a high-throughput in vitro assay will be designed to investigate a number of implant parameters, as well as the integrity and biostability of the retinal implant using retinal pigment epithelial cells. Additionally, medical device sealants will be investigated in this in vitro study, and the functional integrity of the implant will be measured using time-resolved absorption spectroscopy and an ion-sensitive detector, which is being developed specifically for this application. Lastly, this ion-sensitive detector will provide an opportunity to further measure the spatial sensitivity of the retinal implant with high resolution. These in vivo and in vitro studies are vital for the continued evaluation of biocompatibility, surgical feasibility, and efficacy of the implant. The results from these studies will further demonstrate the commercial viability of the technology under development.