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

这个PFI: AIR技术翻译项目的重点是翻译新的，dna修饰的胶原蛋白敷料，以填补对改善伤口产品的需求，治愈慢性伤口。dna修饰的胶原蛋白敷料是一项重要的发展，因为它将解决抑制慢性伤口管理现有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-导致不完全愈合和严重的副作用。该项目将产生一种概念验证dna修饰胶原蛋白敷料，有可能填补高级伤口护理的重要市场需求，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。具体来说，该项目采用了一种独特的方法，利用模拟胶原蛋白的“肽”（CMP）分子，将编码生长因子的DNA整合到胶原蛋白凝胶“支架”（CMPGs）中，来制造基于凝胶的敷料。这种将基因构建物纳入胶原蛋白支架的方法允许基因构建物在较长时间内保持在伤口床内的定位和保护，但随着愈合的开始，基因构建物很容易被释放以刺激进一步的愈合活性。与之竞争的高级伤口敷料，主要基于胶原基质或局部生长因子（PDGF-BB），仍然显示出约50%的伤口愈合率，担心生长因子的毒性。相比之下，基于cmpg的技术已经显示出(i) 3D模型伤口完全愈合，与商业方法相比，只需要1/10的生长因子；（ii）在小鼠伤口模型中持续活动数周。这些特征表明其明确的潜力，为患者提供改善伤口愈合显著较少的管理，较低的生长因子剂量，更少的副作用。CMPG设计策略解决了从研究发现到商业应用的几个重要技术差距。具体来说，多篇报道明确描述了不溶性（基质）和可溶性信号因子在伤口修复中的协同作用，这表明需要对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，因为它会影响CMPG凝胶溶液的部署，以及应用后凝胶的稳定性。因此，通过评估纳米结构结合如何影响凝胶特性，进而阐明凝胶特性和细胞基因调控如何协同增强组织修复，从而为慢性伤口修复的临床难题带来新材料和治疗策略，将产生新的知识价值。参与该项目的博士后将通过参加特拉华大学的正式课程（例如：商业管理和市场需求），接受知识产权、监管问题和市场需求方面的培训。“高科技创业”)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定位。该项目与特拉华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，同时也定位CMPG技术，以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.