Development and Characterization of a Collagen-Based Matrix for Vascularization and Cell Delivery

© Cara E. Ellis et al. 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

*, Address correspondence to: Gregory S. Korbutt, PhD, Alberta Diabetes Institute, University of Alberta, 5-002 Li Ka Shing Centre for Health Research Innovation, Edmonton, AB, T6G 2E1, Canada, , E-mail: [email protected]

Introduction

Islet transplantation is a promising clinical cell-based therapy for treatment of type 1 diabetes.^1-4 However, despite remarkable progress, the liver implantation site remains far from ideal. Clinical transplantation of islets into the portal vein has been associated with life-threatening intraperitoneal bleeding,⁵ portal vein thrombosis, and hepatic steatosis.^6,7 The liver may also contribute to the gradual attrition of chronic islet graft function.⁸ Search for a safer alternative site for islet transplantation is therefore desirable and an important issue to address.⁹ Using biomaterials to deliver islets to an alternate site could be advantageous if vascularization was promoted, particularly if an immune barrier could also be incorporated into the device.⁹ Diverse techniques have been attempted to this end, including utilizing a polyethylene terephthalate mesh bag,¹⁰ a polyurethane foam dressing,¹¹ a stainless steel mesh with polytetrafluoroethylene stoppers,¹² and gelatin microspheres in a collagen-coated polyvinyl bag.¹³ Most devices for islet delivery are based on synthetic polymers, which offer the advantages of complete control over mechanical and chemical properties and lower manufacturing costs^14,15 ; however, natural polymers offer significant advantages of their own, including the ability of their degradation by-products to be metabolized.