New infusible ECM hydrogel for treating acute myocardial infarction

摘要 在美国，心肌梗死后心力衰竭(MI)仍然是主要的死亡原因。每年 据估计，约55万美国人将有新的心肌梗死，约20万人将有复发性心肌梗死，大多数 这些患者将遭受心力衰竭之苦。这些令人震惊的统计数字要求开发新的 缺血性心肌病患者的治疗。组织工程与再生医学战略 为开发治疗这些患者的新疗法提供了巨大的潜力。最近，脱细胞 生物材料在提供功能益处方面显示出巨大的前景，而不会出现与 其他再生医学方法。刺激内源性修复的可注射生物材料是一种 有吸引力的替代方案，因为潜在的治疗方法仍然可以通过导管以微创的方式提供，但 下架，与其他再生医学产品相比，成本显著降低，例如 细胞。因此，Ventrix正专注于无细胞再生医学方法。Ventrix有一段历史 成功开发治疗缺血性心肌病的可注射生物材料。之前的两次NIH SBIR 导致VentriGel获得批准的IND，VentriGel是一种可注射、可经导管释放的水凝胶，源自 去细胞猪心肌。这导致了最近在60天至3天的患者中进行的一期临床试验取得成功 心肌梗死后数年。本文提出的研究是将一种新的生物材料产品推向市场的关键一步 治疗急性心肌梗塞。这种新的可溶版本的VentriGel可以通过冠状动脉内输注进行输送，这将 与需要经心内膜给药的原始配方不同，心肌梗死后立即进行治疗。 在这里，我们将通过优化交付和评估功能来测试翻译这项新技术的可行性 在一个大型动物急性心肌梗塞模型中。这将是首个冠状动脉内不可融合再生生物材料产品。 用于治疗急性心肌梗塞患者。

Summary Heart failure post-myocardial infarction (MI) continues to be the leading cause of death in the U.S. Each year it is estimated that ~550K Americans will have a new MI, and ~200K will have a recurrent MI and a majority of these patients will suffer from heart failure. These staggering statistics necessitate the development of new therapies for patients with ischemic cardiomyopathy. Tissue engineering and regenerative medicine strategies offer significant potential for the development of novel therapies to treat these patients. Recently, acellular biomaterials have shown great promise in providing functional benefit without the complications associated with other regenerative medicine approaches. Injectable biomaterials that stimulate endogenous repair are an attractive alternative since potential therapies could still be delivered minimally invasively via catheter yet could be off the shelf and have significantly reduced costs compared to other regenerative medicine products, such as cells. Ventrix is therefore focusing on cell-free regenerative medicine approaches. Ventrix has a history of success in developing injectable biomaterials for treating ischemic cardiomyopathy. Two previous NIH SBIRs resulted in an approved IND for VentriGel, an injectable, catheter-deliverable hydrogel derived from decellularized porcine myocardium. This led to a recent successful Phase 1 clinical trial in patients 60 days to 3 years post-MI. The study proposed herein is a key step in bringing a new biomaterial product to market for treating acute MI. This new soluble version of VentriGel can be delivered via intracoronary infusion, which will enable treatment immediately post-MI, unlike the original formulation, which required transendocardial delivery. Herein, we will test the feasibility of translating this new technology by optimizing delivery and evaluating function in a large animal acute MI model. This will be the first intracoronary infusible regenerative biomaterial product for treating acute MI patients.