Artificial Cornea Using New Biomaterials

描述(申请人提供)：使用新型生物材料PD/PI Maxwell Maginness博士项目摘要/摘要。我们建议通过一种新的生物材料技术来推进一种新的人工角膜设计的发展，该技术允许方便的整合和巩膜组织重建。该设计提供了良好的视觉效果，与宿主组织稳定和牢固的整合；预计将克服以前人工角膜设计的局限性，并且不需要人类供体组织。早期的动物研究也表明，这种设计允许一种简单的外科植入技术。该提案是针对国家眼科研究所角膜疾病计划下的《开发新型生物材料用于角膜假体》列出的。医学问题：角膜失明覆盖眼前部的透明组织混浊是导致可治疗失明的两个最常见的原因之一。它影响着全球约1200万人。[1]具有人类供体组织的角膜移植为一小部分病情较轻的患者提供了解决方案，全球每年约有10万例这样的手术。这些手术需要眼库的支持，这在世界上许多失明发生率较高的地区是没有的。在发达国家，越来越多的LASIK手术使许多潜在的捐赠者的眼睛无法使用。[2]另一种选择是人工角膜(角膜假体“K-PRO”)。目前有两种FDA批准的设备--波士顿K-Pro[3]和AlphaCor设备[4]。这些与宿主组织的结合不佳，需要复杂的手术植入和漫长的随访。目前，它们只在全国少数几个中心作为最后手段提供(华盛顿大学是其中之一)，留下了许多未得到治疗的病例。建议的解决方案：我们建议的人工角膜设计旨在通过结合以下各项来克服这些限制：清晰、半刚性的光学中心，经证明可提供出色而快速的视觉恢复；基于球形模板血管生成再生(STAR)生物材料结构的多孔性外围设备，以快速实现坚固、稳定、整合良好的宿主组织界面。在整个人工角膜装置结构中使用经过充分验证的具有适当光学和机械性能的生物兼容材料(有机硅)。不需要供体组织。简单的一步外科手术。STAR[5]最初由Buddy Ratner博士领导下的华盛顿大学生物材料工程实验室开发，是一种多孔3D生物材料，具有独特的、严格控制的几何形状，可增强组织附着、生长和血运重建。该结构可以由各种衬底材料制成，包括已经广泛用于其他眼科设备(例如青光眼分流术、人工晶状体)的生物兼容硅橡胶。Healionics公司拥有独家许可证，并正在将各种形式的明星材料商业化，用于各种医疗应用。对兔巩膜中的星形生物材料结构的初步研究表明，成功的人工角膜需要快速的组织整合和理想的重建、血管化、无纤维化愈合模式。这项建议的主要目的是将Healionics Corporation的生物材料能力与威斯康星大学眼科的Ratner博士和沈博士所做的体外和体内可行性研究相结合，以指导下一步开发人造角膜的工作。更好的构建方法、外周组织粘附性研究、耐久性测试和体内研究的扩展就是为了这个目标而提出的发展。较长远的目标是根据这项建议所取得的结果，改善设计，进行更广泛的研究，并最终供人类使用。关键词：人工角膜，多孔生物材料，可治疗的失明，角膜移植手术。公共卫生相关性：角膜混浊是导致失明的主要原因。使用供体角膜在许多情况下并不适用，到目前为止发展起来的人工角膜已经显示出严重的局限性。一种新的生物材料结构的开发极大地改善了巩膜组织的整合和良好的光学性能，显示了克服其中许多问题的潜力，并使改进的假体的建造和应用成为可能。在这里提出的步骤的成功可能最终导致视力恢复覆盖比目前方法可能覆盖的更广泛的人群。

DESCRIPTION (provided by applicant): Artificial Cornea Using New Biomaterials PD/PI Maxwell Maginness PhD Project Summary/Abstract. We propose to advance the development of a novel artificial cornea design enabled by a new biomaterial technology permitting facile integration and sclera tissue reconstruction. The design offers potential for an excellent visual outcome, stable and robust integration with the host tissue; is anticipated to overcome limitations of previous artificial cornea designs and does not require human donor tissue. Early animal studies also suggest that the design allows for a simple surgical implantation technique. The proposal is directed at the National Eye Institute Corneal Diseases Program under the "development of new biomaterials for corneal prostheses" listing. The Medical Problem: Corneal blindness opacification of the transparent tissue covering the front of the eye is one of the two most prevalent causes of treatable blindness. It affects some 12 million people worldwide. [1] Corneal transplants with human donor tissue offer solutions for a fraction of patients with less severe disease, with approximately 100,000 such procedures worldwide every year. These procedures require the support of eye banks, not available in many world regions with a high incidence of blindness. In developed countries increasing numbers of LASIK procedures are rendering many potential donor eyes unusable. [2] The alternative is an artificial cornea (Keratoprothesis "K-pro"). There are two currently available FDA- approved devices - the Boston K-Pro [3] and the AlphaCor device [4]. These show poor integration with host tissue and require complex surgical implantation with lengthy follow-up. Presently they are offered only as a last resort in a few centers nationwide (University of Washington is one of them), leaving many untreated cases. Proposed Solution: Our proposed artificial cornea design aims to overcome these limitations a by combining: A clear, semi rigid optical center, proven to provide excellent and rapid visual recovery A porous periphery based on Spherically Templated Angiogenic Regenerative (STAR) biomaterial structure to rapidly achieve a robust, stable, well-integrated host tissue interface. Use of well proven biocompatible materials (silicones) with appropriate optical and mechanical properties for the entire artificial cornea device structure. No donor tissue required. Simple, one step surgical procedure. Originally developed at the University of Washington Engineered Biomaterials Laboratory under Dr Buddy Ratner, (mentoring this project) STAR [5] is a porous 3D biomaterial with a unique, tightly controlled geometry enhancing tissue attachment, in-growth and revascularization. The structure may be made from a variety of substrate materials, including biocompatible silicone rubbers as already widely used in other ophthalmic devices (e.g. glaucoma shunts, IOL's). Healionics Corporation holds exclusive license and is commercializing forms of the STAR material for a variety of medical applications. Preliminary studies with STAR biomaterial structures in the rabbit sclera have shown the rapid tissue integration and desirable reconstructive, vascularized, afibrotic healing patterns needed for a successful prosthetic cornea. The primary aim of this proposal is to extend and combine the biomaterials capability of Healionics Corporation with the in vitro and in vivo feasibility studies done by Dr. Ratner and Dr. Shen of UW Ophthalmology towards the next steps in developing an artificial cornea. The proposed developments of better construction methods, periphery tissue adhesion studies, durability testing and an extension of in vivo studies, are directed to this goal. The longer term aim is to refine the designs in the light of results obtained under this proposal, proceed to a more extensive study and eventually to human use. Keywords: Artificial cornea, porous biomaterials, treatable blindness, corneal transplant surgery. PUBLIC HEALTH RELEVANCE: Corneal opacity is a major cause of blindness. Use of donor corneas is not applicable for many cases and artificial corneas developed to date have shown serious limitations. The development of a new biomaterial structure with greatly improved sclera tissue integration and excellent optics shows potential to overcome many of these issues and allow construction and application of an improved prosthesis. Success with the steps proposed here may lead eventually to sight restoration covering a much wider population than is possible with present methods.