权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

PFI:AIR - TT: DNA-LINKED ECM GELS FOR ENHANCED HEALING IN CHRONIC WOUNDS

PFI:AIR - TT：DNA 连接 ECM 凝胶可增强慢性伤口的愈合能力

基本信息

批准号：
1700980
负责人：
Millicent Sullivan
金额：
$ 20万
依托单位：
University of Delaware
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2019-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1700980&HistoricalAwards=false
关键词：
PFI AIR TT DNA LINKED

项目摘要

This PFI: AIR Technology Translation project focuses on translating new, DNA-modified collagen dressings to fill the need for improved wound products that heal chronic wounds. DNA-modified collagen dressings are an important development because they will address two key shortcomings inhibiting success of existing treatments for chronic wound management - insufficient bioactivity/stability and high growth factor dosing - that lead to incomplete healing and serious side effects. This project will result in a proof-of-concept DNA-modified collagen dressing with the potential to fill a significant market need in advanced wound care, a growing segment in which the global market is projected to approach $15B by the year 2020. Specifically, the project uses a unique approach to create gel-based dressings employing collagen-mimetic "peptide" (CMP) molecules to integrate growth factor-encoding DNA into collagen gel "scaffolds" (CMPGs). This method for incorporating gene constructs into collagen scaffolds allows the gene constructs to remain localized and protected within the wound bed over extended time frames, yet as healing initiates, the gene constructs are released readily to stimulate further healing activity. Competing advanced wound dressings, which are largely based on collagen matrices or topical growth factor (PDGF-BB), have continued to show wound closure rates of ca. 50%, with concerns over growth factor toxicity. In contrast, the CMPG-based technology has shown (i) complete healing of 3D model wounds, requiring only 1/10 the growth factor necessary as compared with commercial approaches and (ii) sustained activity in a mouse wound model over periods of multiple weeks. These features indicating its definitive potential to offer patients improved wound healing with significantly fewer administrations, lower growth factor dosing, and fewer side effects.The CMPG design strategy addresses several important technology gaps as it translates from research discovery toward commercial application. Specifically, multiple reports delineate the clear synergies in wound repair between insoluble (matrix) and soluble signaling factors, suggesting that dual optimization of CMPG gene delivery and matrix composition is needed to maximize healing potential. At the same time, the matrix composition also has clear implications for clinical usage, as it will impact the ease with which CMPG gel solutions can be deployed, and the stability of the resulting gels after application. Hence, new intellectual merit will be generated by evaluating how nanostructure incorporation affects gel properties, and in turn, by elucidating how gel properties and cellular gene regulation can synergistically enhance tissue repair, leading to new materials and therapeutic strategies for a clinically difficult problem in chronic wound repair. The postdoctoral fellow involved in this project will receive training in intellectual property, regulatory issues, and market need through participation in formal University of Delaware courses (e.g. "High Technology Entrepreneurship") as well as short-courses (e.g. via SBE2 IGERT), which will afford a team well positioned to transition this technology into the commercial environment. The project engages the University of Delaware's Office of Economic Innovation and Partnerships (OEIP), as well as partnerships with specific healthcare companies to enable further intellectual property development and large-scale market analysis, while also positioning the CMPG technology to fill specific needs in wound care technologies.

该PFI：AIR技术翻译项目专注于翻译新的DNA改性胶原蛋白敷料，以满足对改善伤口产品的需求，从而治愈慢性伤口。DNA修饰的胶原蛋白敷料是一项重要的发展，因为它们将解决阻碍现有慢性伤口管理治疗成功的两个关键缺点-生物活性/稳定性不足和高生长因子剂量-导致愈合不完全和严重副作用。该项目将产生一种概念验证的DNA改性胶原蛋白敷料，有可能满足高级伤口护理的重大市场需求，这是一个不断增长的领域，预计到2020年全球市场将接近150亿美元。具体来说，该项目使用一种独特的方法来创建基于凝胶的敷料，采用胶原模拟“肽”（CMP）分子将生长因子编码DNA整合到胶原凝胶“支架”（CMPG）中。这种将基因构建体掺入胶原支架中的方法允许基因构建体在延长的时间范围内保持定位并保护在伤口床内，然而随着愈合开始，基因构建体容易释放以刺激进一步的愈合活性。主要基于胶原蛋白基质或局部生长因子（PDGF-BB）的竞争性高级伤口敷料继续显示出约10%的伤口闭合率。50%，担心生长因子毒性。相比之下，基于CMPG的技术已经显示（i）3D模型伤口的完全愈合，与商业方法相比仅需要1/10的生长因子，以及（ii）在小鼠伤口模型中持续多周的持续活性。这些特征表明其具有明确的潜力，为患者提供改善伤口愈合的显著更少的管理，更低的生长因子剂量，和更少的副作用。CMPG的设计策略解决了几个重要的技术差距，因为它从研究发现转化为商业应用。具体而言，多个报告描述了不溶性（基质）和可溶性信号传导因子之间在伤口修复中的明显协同作用，表明需要CMPG基因递送和基质组成的双重优化以最大化愈合潜力。同时，基质组合物也对临床使用具有明确的影响，因为它将影响CMPG凝胶溶液部署的容易性以及应用后所得凝胶的稳定性。因此，新的知识价值将产生通过评估纳米结构的掺入如何影响凝胶性能，并反过来，通过阐明凝胶性能和细胞基因调控如何协同增强组织修复，导致新的材料和治疗策略的临床难题在慢性伤口修复。参与该项目的博士后研究员将通过参加正式的特拉华州大学课程（例如“高科技创业”）以及短期课程（例如通过SBE 2 IGERT）接受知识产权，监管问题和市场需求方面的培训，这将为团队提供良好的定位，将该技术转化为商业环境。该项目与特拉华州大学经济创新与合作办公室（OEIP）合作，并与特定的医疗保健公司合作，以实现进一步的知识产权开发和大规模市场分析，同时还将CMPG技术定位为满足伤口护理技术的特定需求。