I-Corps: Tissue reparative cardiovascular disease technology

这个i-Corps项目的更广泛的影响/商业潜力是开发一种组织工程技术，该技术将能够产生能够拉伸和回缩的心血管(CV)组织替代物，并能够根据需要对因疾病而结构中断的血管进行现场再生修复。这项技术解决了目前组织工程方法无法克服成年细胞产生蛋白质弹性蛋白的能力差的问题，这种蛋白质弹性蛋白构成了提供组织拉伸性能的弹性纤维的主要成分。拟议的创新是一种修复性纳米颗粒平台技术，包括抗体靶向、具有弹性蛋白原再生和抗降解性能的可生物降解聚合物纳米配方。在这个项目中，这项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转的弹性基质破裂而导致的腹主动脉壁局部扩张。通过i-Corps项目，该团队将评估这项技术的商业可行性，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。i-Corps项目基于一种新型聚合物纳米颗粒传递方法的变革潜力提供智力优势，用于疾病受损弹性组织的现场再生修复，这种方法模仿干细胞分泌的弹性基质再生效应。这项技术将首先在修复腹主动脉瘤(AAA)的背景下进行测试，因为目前还没有FDA批准的治疗腹主动脉瘤的药物治疗方法，而且对小AAA进行选择性手术和支架植入术风险很高，而且没有治疗益处。该团队将基于包含抗体靶向可生物降解聚合物基质的再生纳米颗粒确定最低可行产品。这些纳米颗粒的前弹性蛋白再生和抗基质降解特性是由释放的活性物质(从成人干细胞来源的平滑肌细胞鉴定的生物因子)和化学功能化的聚合物基质独立提供的。如果成功，这项技术将提供现实的前景，在诊断后不久阻止或逆转小型AAA的增长，从而减少这些患者的手术需求。

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.