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A Biodegradable Vascular Coupling Device for End-to-End Anastomosis

用于端端吻合的可生物降解血管耦合装置

基本信息

批准号：
9764480
负责人：
Jayant Prasad Agarwal
金额：
$ 71.62万
依托单位：
MICROSURGICAL INNOVATIONS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-22 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9764480
关键词：
Anastomosis - action Animal Model Animals Arteries Back Benchmarking Biocompatible Materials Blood Vessels Blood flow Caliber Child Chronic Coupled Coupling Data Devices Effectiveness Engineering Failure Family suidae Foreign Bodies Funding Gold Grant Hand Histology Human Hypoxia Image Interview Laboratories Laboratory Animal Production and Facilities Learning Longitudinal Studies Marketing Mechanics Methods Microsurgery Molds Operative Surgical Procedures Outcome Paper Performance Phase Physiological Plastic Surgical Procedures Preparation Publishing Readiness Research Series Societies Stents Surgeon Suture Techniques Technology Testing Thinness Time Universities Utah Veins Work arm base biomaterial compatibility caprolactone cohort commercialization cost design healing human error implantation in vivo innovation mechanical properties meetings metallicity mid-career faculty poly(lactic acid)product development professor prototype repaired response seal symposium tool tool development

项目摘要

Project Summary The objective of Microsurgical Innovations (MSI) in this proposal is to develop a biodegradable vascular coupling device (VCD), which would replace the hand suturing technique currently used to connect arteries and veins in microvascular and macrovascular end-to-end vascular repair surgeries. Our device works for both arteries and veins and can rapidly connect the two vessel ends together in a watertight seal without leaving any foreign material in the lumen to come in contact with flowing blood. We have manufactured prototype devices using biodegradable poly(lactic acid-co-caprolactone) (PLACL (95% PLA and 5% caprolactone)) with no moving parts in multiple sizes to accommodate varying vessel size in a range of vascular repair scenarios). This device has similarities to the already available Synovis vein coupling device (now part of Baxter) in that it will be made of biocompatible materials, but significantly differs from the Synovis device in that it does not have any metallic parts, is completely biodegradable, can be used easily for both arteries and veins and the anastomosis can be performed much more rapidly. This approach would reduce the time required in the surgery suite, reduce costs associated with surgery, and reduce the likelihood of failure of the anastomosis, by minimizing human error and stenting open the anastomosis. The biodegradable device will be useful in cases of chronic need of increased blood flow requirement e.g. hypoxia or growing child. Our product will contain a sizing tool, inner ring between 1.0 mm to 4.00 mm at 0.5 mm intervals and a gap between the inner ring and outer ring ranging from 0.1 mm, 0.2 mm and 0.3 mm, and installation tools. The technology at the center of this proposal has been developed at the University of Utah and has been licensed to MSI, a recent spin-out company from the University. We have produced a series of prototypes between 1-7 mm size range that are applicable to microsurgery and have tested our device successfully in multiple animals for 1 to 3 month long studies. Multiple papers by our team have been published in the last few years. For successful commercialization of this device we need to (i) develop and characterize devices for small caliber vessels (customer need identified by interviewing over 70 surgeons), (ii) long term study (device degradation, intima to intima healing, patency), (iii) mold and tool development with manufacturing in GMP certified facilities, (iV) biocompatibility testing, and (V) 510 K application. Specific aims are geared towards moving MSI’s VCD through product commercialization pipeline as reflected by our research strategy. As part of state and university funded lean canvas cohorts, we conducted more than 100 interviews (>75 surgeons including 19 at the Mountain West Plastic Surgery Society meeting in March 2017 hosted by Jay Agarwal). We learned that the readiness of the device for market acceptance required that the overall size of the VCD be reduced by about 50%, that demonstration of 1.5 to 2.00 mm devices was needed, and comparison data with gold standards was desired. Our Aims for Phase II reflect this learning in addition to doing work necessary to obtain regulatory approval. Hypothesis 1.The biodegradable vascular coupling device can provide the necessary coupling strength in physiological conditions for 1.0 mm to 3.00 mm blood vessels. Specific Aim 1. To evaluate the functionality of vascular coupling devices 1.5 mm to 3.00 mm diameter ex vivo Hypothesis 2. Vascular anastomosis can be performed with the biodegradable vascular coupling device in vivo for small caliber vessels (1.5 mm to 3.00 mm diameter). The implantation will not affect blood vessel patency and no severe foreign body response will occur. Specific Aim 2. To evaluate the effectiveness and performance of small diameter biodegradable coupling devices in vivo. Hypothesis 3. Vascular anastomosis time with the biodegradable vascular coupling device will be lower than gold standard methods. Specific Aim 3. To evaluate the effectiveness and compare performance of the biodegradable coupling device in vivo with gold standards for larger diameter artery and vein (3.0 to 4.5 mm). Hypothesis 4. A. The PLA-based vascular coupling device can be manufactured using GMP certified facilities. B. The PLACL based vascular coupling device is biocompatible. Specific Aim 4. A. To manufacture vascular coupling device molds and parts. B. To conduct comprehensive biocompatibility testing with a third party (Nelson laboratories) for MSI’s vascular coupling device.

项目概要显微外科创新公司 (MSI) 在该提案中的目标是开发一种可生物降解的血管耦合装置（VCD），它将取代目前用于连接微血管和静脉中的动脉和静脉的手工缝合技术大血管端对端血管修复手术。我们的设备适用于动脉和静脉，可以快速连接两个容器以水密密封的方式连接在一起，不会在管腔中留下任何异物来接触流动的血液。我们使用可生物降解的聚（乳酸-己内酯）（PLACL）制造了原型设备（95% PLA 和 5% 己内酯）），多种尺寸均无活动部件，可适应各种尺寸的容器血管修复场景）。该装置与现有的 Synovis 静脉耦合装置（现已成为 Baxter），因为它将由生物相容性材料制成，但与 Synovis 设备显着不同，因为它不无金属部件，完全可生物降解，可轻松用于动脉、静脉及吻合术可以更快地执行。这种方法将减少手术室所需的时间，降低成本与手术相关，并通过最大限度地减少人为错误和支架置入来减少吻合失败的可能性打开吻合口。可生物降解的装置在长期需要增加血流量的情况下将很有用例如缺氧或成长中的孩子。我们的产品将包含一个定径工具，内圈在 1.0 毫米到 4.00 毫米之间，0.5 毫米内圈和外圈之间的间隔和间隙为0.1毫米、0.2毫米和0.3毫米，以及安装工具。该提案的核心技术是由犹他大学开发的，并已授权给 MSI，一家最近从大学衍生出来的公司。我们生产了一系列尺寸范围在 1-7 毫米之间的原型适用于显微外科手术，并已在多只动物身上成功测试了我们的设备，进行了 1 至 3 个月的研究。我们团队在过去几年中发表了多篇论文。为了该设备的成功商业化，我们需要 (i) 开发和表征小口径容器的设备（通过采访 70 多名外科医生确定客户需求），(ii) 长期研究（设备退化、内膜到内膜 (iii) 模具和工具开发以及在 GMP 认证设施中制造，(iV) 生物相容性测试， (V) 510 K 申请。具体目标是通过产品商业化渠道推动 MSI 的 VCD 正如我们的研究策略所反映的那样。作为州和大学资助的精益画布队列的一部分，我们进行了超过 100 次采访（>75 名外科医生，其中 19 名参加了 2017 年 3 月主办的西山整形外科协会会议杰·阿加瓦尔）。我们了解到，该设备要为市场接受做好准备，需要 VCD 的整体尺寸减少约50％，需要1.5至2.00毫米器件的演示，以及与黄金的比较数据需要标准。我们第二阶段的目标除了完成获得监管所需的工作外还反映了这种学习赞同。假设1.可生物降解的血管耦合装置能够提供生理所需的耦合强度 1.0毫米至3.00毫米血管的条件。具体目标 1. 离体评估直径 1.5 mm 至 3.00 mm 的血管耦合装置的功能假设2.可生物降解血管耦合装置可在体内对小血管进行血管吻合口径容器（直径 1.5 毫米至 3.00 毫米）。植入不会影响血管通畅，无严重异物身体就会发生反应。具体目标 2. 评估小直径可生物降解耦合装置在体内的有效性和性能。假设3.使用可生物降解血管耦合装置的血管吻合时间将低于金标准方法。具体目标 3. 评估可生物降解耦合装置的有效性并比较体内可生物降解耦合装置的性能较大直径动脉和静脉（3.0 至 4.5 毫米）的金标准。假设 4. A. 基于 PLA 的血管耦合装置可以使用 GMP 认证的设施进行制造。 B.PLACL 基于血管耦合装置具有生物相容性。具体目标 4. A. 制造血管连接装置模具和零件。 B、全面开展与第三方（尼尔森实验室）对 MSI 的血管耦合装置进行生物相容性测试。