Targeted Oxygen Delivery to Wounds: Using a Novel, Tunable, Oxygen Delivery Tech

描述(由申请人提供)： 该项目将开发一种新的氧结合蛋白(H-NOX蛋白)，作为慢性伤口的局部治疗。这些蛋白质旨在深入伤口，输送氧气，促进伤口愈合。慢性伤口(超过8周无法愈合的伤口)是一个重大的医疗问题，也是一个特别影响日益增长的人口的问题，包括肥胖、糖尿病患者和免疫功能受损的患者。氧气在伤口愈合中有许多重要作用，临床研究表明，增加伤口中的氧气可以促进伤口愈合。使用局部蛋白质溶液的临床有益的氧气输送系统可以改善数百万患者的临床结果，提高标准伤口治疗的有效性，并降低与慢性伤口及其后果治疗相关的成本。H-NOX蛋白(用于血红素-一氧化氮结合蛋白)是加州大学伯克利分校发现和开发的一项革命性的氧气输送技术，并由Omniox独家授权。初步数据显示，H-NOX蛋白成功地为缺血组织提供了氧气。在这个项目中，H-NOX蛋白将作为一种局部治疗方法在两个小鼠伤口模型中进行测试，以促进伤口愈合。首先，H-NOX蛋白将被优化，以向低氧环境中的低氧小鼠皮肤伤口输送氧气。然后，H-NOX蛋白将在糖尿病创面的小鼠模型中进行测试，以显示(1)H-NOX蛋白质深入伤口组织，为伤口和伤口周围组织充氧，(2)H-NOX蛋白质改善伤口中的颗粒化和血管形成过程，最重要的是，在缓慢愈合的糖尿病创面的小鼠模型中，H-NOX蛋白质可以加速伤口的整体愈合。H-NOX氧传递蛋白促进小鼠伤口愈合的研究将为人类创伤愈合H-NOX蛋白的早期临床开发奠定基础。一种可以局部应用于人体伤口、输送氧气并改善愈合的H-NOX氧气输送溶液将是患者和护理人员的重要发展，他们管理着治疗缓慢愈合的慢性伤口的重大临床和生活质量负担。 公共卫生相关性： 该项目将使用突破性的氧气输送技术来增加伤口中的氧气，促进伤口愈合。我们将展示新的氧传递蛋白可以将氧气传递到创伤组织，并深入到伤口组织，促进伤口愈合。将蛋白质应用于伤口并促进伤口愈合的能力将对数百万遭受慢性、缓慢愈合伤口的患者产生重大的治疗影响。

DESCRIPTION (provided by applicant): This project will develop a novel class of oxygen binding proteins (H-NOX proteins) as a topical treatment for chronic wounds. These proteins are designed to penetrate deep into wounds, deliver oxygen, and improve wound healing. Chronic wounds (wounds that fail to heal over more than 8 weeks) are a significant medical problem and an issue that specifically affects a growing population including the obese, diabetics, and immune compromised patients. Oxygen has a number of important roles in wound healing and clinical studies have shown that increasing oxygen in wounds can accelerate wound healing. A clinically beneficial oxygen delivery system utilizing a topical protein solution could improve clinical outcomes for millions of patients, improving the effectiveness of standard wound therapy and reducing the costs associated with the treatment of chronic wounds and their consequences. The H-NOX proteins (for heme-nitric oxide binding proteins) are a revolutionary oxygen delivery technology discovered and developed at UC Berkeley and exclusively licensed to Omniox. Preliminary data suggest H-NOX proteins successfully oxygenate ischemic tissue. In this project, the H-NOX proteins will be tested as a topical treatment to improve wound healing in two mouse wound models. First, H-NOX proteins will be optimized to deliver oxygen to the low oxygen environment of a hypoxic mouse skin wound. Then, H-NOX proteins will be tested in a mouse model for diabetic wounds to show (1) that H-NOX proteins penetrate deep into the wound tissue to oxygenate the wound and the tissue surrounding the wound and (2) H-NOX proteins improve the processes of granularization and vascularization in the wounds and, most importantly, accelerate overall wound healing in the mouse model of slow-healing diabetic wounds. Demonstration of improved mouse wound healing due to H-NOX oxygen delivery proteins will be the foundation for early clinical development of H-NOX proteins for human wound healing. An H- NOX oxygen delivery solution that could be applied topically to human wounds, deliver oxygen, and improve healing would be an important development for patients and caregivers who manage the significant clinical and quality-of-life burden of treating slow-healing chronic wounds. PUBLIC HEALTH RELEVANCE: This project will use a breakthrough oxygen delivery technology to increase oxygen in wounds and improve wound healing. We will demonstrate that novel oxygen delivery proteins can deliver oxygen to wounded tissue and also penetrate deep into wound tissue and accelerate wound healing. The ability to apply protein to wounds and enhance wound healing will have a significant therapeutic impact for the millions of patients who suffer chronic, slow healing wounds.