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

这个PFI：空气技术翻译项目专注于翻译新的DNA修饰的胶原蛋白敷料，以满足对治愈慢性伤口的改进伤口产品的需求。DNA修饰的胶原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陷-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的副作用。该项目将产生一种概念验证DNA修饰的胶原敷料，有可能满足高级伤口护理的巨大市场需求，这是一个不断增长的细分市场，预计到2020年全球市场将接近150亿美元。具体地说，该项目使用一种独特的方法来创造基于凝胶的敷料，该敷料使用胶原肽(CMP)分子将编码生长因子的DNA整合到胶原胶“支架”(CMPGs)中。这种将基因构建物整合到胶原支架中的方法允许基因构建体在延长的时间框架内保持在伤口床内并受到保护，但随着愈合的开始，基因构建体很容易被释放，以刺激进一步的愈合活动。与之竞争的先进创面敷料主要基于胶原基质或局部生长因子(PDGF-BB)，由于担心生长因子的毒性，创面闭合率继续保持在50%左右。相比之下，基于CMPG的技术显示：(I)3D模型伤口完全愈合，与商业方法相比，只需要1/10的必要生长因子；(Ii)在小鼠伤口模型中持续活动数周。这些特点表明，它具有显著减少给药次数、减少生长因子剂量和副作用的情况下为患者提供改善伤口愈合的绝对潜力。CMPG设计策略解决了从研究发现转化为商业应用的几个重要技术差距。具体地说，多篇报道描述了难溶(基质)和可溶信号因子在伤口修复中的明显协同作用，提示需要对CMPG基因传递和基质组成进行双重优化，以最大限度地发挥愈合潜力。同时，基质组成对临床使用也有明显的影响，因为它将影响CMPG凝胶溶液的易部性以及使用后所得凝胶的稳定性。因此，通过评估纳米结构掺入如何影响凝胶特性，并反过来通过阐明凝胶特性和细胞基因调控如何协同促进组织修复，将产生新的智力优势，从而为慢性伤口修复中的临床难题带来新的材料和治疗策略。参与该项目的博士后研究员将通过参加特拉华大学的正式课程(如：高技术创业)以及短期课程(例如通过SBE2 IGERT)，这将为团队提供将这项技术转化为商业环境的良好条件。该项目与特拉华大学经济创新与伙伴关系办公室(OEIP)建立了合作伙伴关系，并与特定的医疗保健公司建立了合作伙伴关系，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。

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.