I-Corps: Tissue reparative cardiovascular disease technology

I-Corps项目更广泛的影响/商业潜力在于开发一种组织工程技术，使心血管（CV）组织替代物能够根据需要伸缩和反冲，也能对因疾病造成结构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年细胞产生弹性蛋白的能力差的问题，弹性蛋白是提供组织拉伸性能的弹性纤维的主要成分。提出的创新是一种修复纳米颗粒平台技术，包括抗体靶向，具有促弹性蛋白再生和抗降解特性的可生物降解聚合物纳米配方。在该项目中，该技术将首先在治疗腹主动脉瘤（AAAs）的背景下进行验证，腹主动脉瘤是由不可逆的弹性基质破裂引起的腹主动脉壁局部扩张。通过这个I-Corps项目，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，为商业创业创造现实的商业画布。I-Corps项目基于一种新型聚合物纳米颗粒递送方法的变革潜力提供了知识价值，这种方法可以模拟干细胞分泌物的弹性基质再生效果，用于现场再生修复受损的弹性组织。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批准的针对腹主动脉瘤的药物治疗方法，而且小腹主动脉瘤的选择性手术和支架移植风险高，而且没有治疗效果。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生物可降解聚合物基质。这些纳米颗粒的原弹性蛋白再生和抗基质降解特性是由释放的活性剂（从成人干细胞衍生的平滑肌细胞中鉴定的生物因子）和化学功能化的聚合物基质独立提供的。如果成功，该技术将为在诊断后立即阻止或逆转小AAAs的生长提供现实的前景，从而减少对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.