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

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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.