I-Corps: Medical device to treat liver failure

这个i-Corps项目的更广泛的影响/商业潜力是开发一种先进的多器官替代系统，最初专注于治疗肝功能衰竭。目前，当肝脏衰竭时，肝移植是唯一的生存选择，然而，需要肝移植的人中只有十分之一接受了肝移植。肝脏支持系统旨在让患者在等待肝脏恢复或器官可用的同时保持生命。然而，目前的肝脏支持系统还不能延长接受移植和存活的生命。这项拟议的技术可能会为以前无法治疗的肝脏和多器官衰竭患者提供治疗，并在其他医疗程序中防止肝功能衰竭，例如基因治疗和癌症肿瘤切除手术。其目标是为移植提供一座桥梁，并在决定选择谁进行移植时减少种族和性别差异。此外，拟议的技术还可以为被排除在移植之外的患者提供支持。这包括对移植的社会支持不足的人，或者精神疾病或老年等使他们成为贫穷的移植对象的共病。拟议的系统可能扩大可能治疗的潜在条件的范围，并可能为不符合移植条件的患者提供更好的医疗服务。这一i-Corps项目基于开发一种医疗设备，通过去除肝功能衰竭患者的蛋白结合毒素和多余液体来治疗肝功能衰竭。这项拟议的技术使用血液过滤方法，在使用较少透析液的同时，从患者体内去除更多多余的液体。现有的血液滤过系统通常是预稀释的，这意味着在血液通过透析器之前添加替换液。这一过程的缺点是降低了多余液体的去除效率(因为被去除的部分是新添加的置换液)，并降低了毒素去除的效率。后稀释系统以更少的废物去除更多的毒素和多余的液体，但有凝结的风险。建议的再循环血液滤过方法将稀释后的一部分血液再循环回稀释前端口，从而将过量液体使用和凝血风险降至最低。该系统还包括使用白蛋白透析、木炭和漂洗方案来提高蛋白质结合毒素去除效率的方法。该系统的原型在患者中实现了80%的28天存活率，其中20%的患者因危重疾病而预计存活率为20%。此外，这可能会提高蛋白质结合毒素的去除效率，改善治疗结果，并将患者与移植联系起来。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of an advanced multi-organ replacement system that initially focuses on treating liver failure. Currently, when the liver fails, liver transplants are the only option for survival, however, only one in ten people who need a liver transplantation receive it. Liver support systems aim to keep patients alive while waiting for their liver to recover or for an organ to become available. However, current liver support systems have not been able to extend life long enough to receive transplantation and survive. The proposed technology may provide treatment for previously untreatable liver and multi-organ failure patients, as well as preventing liver failure during other medical procedures such as gene therapy and surgery for cancerous tumor removal. The goal is to provide a bridge to transplantation, as well as reduce racial and gender disparities in determining who is selected for a transplant. In addition, the proposed technology also may provide support for patients excluded from transplantation. This includes people with insufficient social support for transplantation, or comorbidities such as mental illness or old age that make them poor transplant candidates. The proposed system may extend the potential range of conditions where treatment is possible and may provide transplant-ineligible patients with better healthcare access.This I-Corps project is based on the development of a medical device to treat liver failure by removing protein bound toxins and excess fluid from liver failure patients. The proposed technology uses a hemofiltration method to remove a greater quantity of excess fluid from the patient while using less dialysate. Existing hemofiltration systems are typically predilution, meaning that replacement fluid is added before the blood passes through the dialyzer. This process has the disadvantages of reducing the efficiency of excess fluid removal (because some of what is removed is the newly added replacement fluid) and reducing the efficiency of toxin removal. Post-dilution systems remove more toxin and excess fluid with less waste, but have a risk of coagulation. The proposed recirculation hemofiltration method recirculates a portion of the blood after post-dilution back to a pre-dilution port, which minimizes excessive fluid usage and coagulation risk. This system also includes methods to increase the efficiency of protein-bound toxin removal using albumin dialysis, charcoal, and a rinsing protocol. A prototype of the system achieved 80% 28-day survival in patients where 20% survival was expected due to critical illness. In addition, this may allow an increase in the efficiency of protein bound toxin removal, improving treatment outcomes and bridging patients to transplantation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.