I-Corps: Tissue reparative cardiovascular disease technology

I-Corps：心血管疾病组织修复技术

• 批准号: 1739042
• 负责人: Anand Ramamurthi
• 金额: $ 5万
• 依托单位: Cleveland Clinic Foundation
• 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: 2017-06-15 至 2018-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1739042&HistoricalAwards=false
• 关键词: Corps; Tissue; reparative; cardiovascular; disease

The broader impact/commercial potential of this I-Corps project is the development of a tissue engineering technology that will enable generation of cardiovascular (CV) tissue replacements capable of stretch and recoil, on demand and also on site regenerative repair of blood vessels which are structurally disrupted due to disease. The technology addresses the inability of current tissue engineering approaches to overcome poor ability of adult cells to generate the protein elastin that form the primary component of elastic fibers that provide tissues stretch properties. The proposed innovation is a reparative nanoparticle platform technology comprising antibody-targeted, biodegradable polymer nanoformulations with pro-elastin regenerative and anti-degradative properties. In this project, the technology will be initially validated in the context of treating abdominal aortic aneurysms (AAAs), which are localized expansions of the abdominal aorta wall resulting from irreversible elastic matrix breakdown. Through this I-Corps project, the team will assess the commercial viability of this technology, understand key market/customer needs and value propositions, explore partnership opportunities and gain regulatory insight towards generating a realistic business canvas for a commercial startup.This I-Corps project provides intellectual merit based on the transformative potential of a novel polymer nanoparticle delivery approach for onsite regenerative repair of disease compromised elastic tissues, which mimic the elastic matrix regenerative effects of stem cell secretions. The technology will first be tested in context of repairing abdominal aortic aneurysms (AAA), since there are no FDA-approved pharmacologic treatments for AAAs, and elective surgery and stent grafting on small AAAs have high risk and no treatment benefit. The team will identify a minimum viable product based on regenerative nanoparticles comprising antibody-targeted biodegradable polymer matrices. The pro-elastin regenerative and anti-matrix degradative properties of these nanoparticles are independently provided by both the released active agents (biologic factors identified from adult stem cell derived smooth muscle cells) and chemically functionalized polymer matrix. If successful, the technology will provide realistic prospects to arrest or reverse growth of small AAAs soon after diagnosis, thus reducing need for surgery in these patients.

该 I-Corps 项目更广泛的影响/商业潜力是组织工程技术的开发，该技术将能够生成能够按需拉伸和回缩的心血管 (CV) 组织替代物，并对因疾病而结构性破坏的血管进行现场再生修复。该技术解决了当前组织工程方法无法克服成体细胞生成弹性蛋白能力差的问题，弹性蛋白是提供组织拉伸特性的弹性纤维的主要成分。所提出的创新是一种修复性纳米颗粒平台技术，包括具有前弹性蛋白再生和抗降解特性的抗体靶向、可生物降解聚合物纳米制剂。在该项目中，该技术将在治疗腹主动脉瘤（AAA）的背景下进行初步验证，腹主动脉瘤是由于不可逆的弹性基质破坏导致的腹主动脉壁的局部扩张。通过这个 I-Corps 项目，该团队将评估该技术的商业可行性，了解关键市场/客户需求和价值主张，探索合作机会并获得监管洞察力，为商业初创公司生成现实的商业画布。该 I-Corps 项目提供了基于新型聚合物纳米颗粒递送方法的变革潜力的智力价值，该方法可对疾病受损的弹性组织进行现场再生修复，该方法模仿了 干细胞分泌物的弹性基质再生作用。该技术将首先在修复腹主动脉瘤（AAA）的背景下进行测试，因为目前尚无 FDA 批准的针对 AAA 的药物治疗方法，并且对小 AAA 进行择期手术和支架移植具有高风险且没有治疗益处。该团队将确定一种基于再生纳米颗粒的最小可行产品，该纳米颗粒包含抗体靶向的可生物降解聚合物基质。这些纳米粒子的促弹性蛋白再生和抗基质降解特性是由释放的活性剂（从成体干细胞衍生的平滑肌细胞中鉴定出的生物因子）和化学功能化的聚合物基质独立提供的。如果成功，该技术将为诊断后不久阻止或逆转小 AAA 的生长提供现实前景，从而减少这些患者的手术需求。