Vascularized regenerative biomaterials for medical devices and cell therapy

虽然胰岛移植对于1%的加拿大胰岛素依赖型（1型）糖尿病患者来说是一种很有希望的治疗方法，但在目前的方案中，大多数胰岛（约60%）在移植后几乎立即丢失。这是由于炎症反应和胰岛附近血管的缺乏，损害了胰岛的生存和功能。我们已经发现了一种独特的材料，可以诱导血管的形成，我们建议使用这种材料（作为涂层或可降解凝胶）来生产一种比目前传统材料更实用的医疗设备（特别是细胞输送设备）。植入式医疗器械的成功使用是建立在惰性生物材料的生物相容性之上的，惰性生物材料产生纤维化反应，将植入物与患者隔离开来，并确保设备的安全性。然而，这种纤维化阻碍了其他设备的成功使用，如葡萄糖传感器或细胞袋用于细胞递送（特别是用于糖尿病的胰岛）。在这项提案中，重点是安大略省公司Sernova生产的一种独特的细胞袋系统，该系统正在开发用于胰岛输送治疗糖尿病。基于MAA（甲基丙烯酸）的独特血管再生生物材料有望增强眼袋内和周围的血管化，从而加快胰岛对糖尿病患者血糖水平升高的反应能力。此外，MAA材料（尤其是可降解凝胶）有望简化Cell Pouch的临床使用（和功效），因为该设备有望一步植入并装载胰岛。

While islet transplantation is a promising treatment for the 1% of Canadians who live with insulin dependent (type 1)diabetes, the majority of islets (perhaps 60%) in current protocols are lost almost immediately upon transplantation. This isdue to inflammatory responses and the lack of blood vessels near the islet which impairs islet survival and function. We havediscovered a unique material that induces the formation of blood vessels and we propose to use this material (as a coatingor as an degradable gel) to generate a medical device (particularly a cell delivery device) that is more functional than iscurrently attainable with conventional materials. The successful use of implantable medical devices is built on thebiocompatibility of inert biomaterials that generate a fibrotic response which isolates the implant from the patient and ensuresthe device is safe. However, this fibrosis precludes the successful use of other devices such as glucose sensors or cellpouches for cell delivery (especially pancreatic islets for diabetes). In this proposal the focus is on a unique Cell PouchSystem produced by an Ontario company, Sernova which is being developed for pancreatic islet delivery to treat diabetes.The unique vascular regenerating biomaterial, based on MAA (methacrylic acid) is expected to enhance vascularization inand around the pouch and so accelerate the ability of islets to respond to elevated glucose levels in diabetic patients.Furthermore the MAA materials (and particularly the degradable gel) are expected to simplify the clinical use (and efficacy ofthe Cell Pouch because it is expected that the device can be implanted and loaded with islets in one step.