Curr Diab Rep (2011) 11:434–444 DOI 10.1007/s11892-011-0210-2 The Use of Biomaterials in Islet Transplantation Danielle J. Borg & Ezio Bonifacio Published online: 12 July 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Pancreatic islet transplantation is a therapeutic option to replace destroyed β cells in autoimmune diabetes. Islets are transplanted into the liver via the portal vein; however, inflammation, the required immunosuppression, and lack of vasculature decrease early islet viability and function. Therefore, the use of accessory therapy and biomaterials to protect islets and improve islet function has definite therapeutic potential. Here we review the application of niche accessory cells and factors, as well as the use of biomaterials as carriers or capsules, for pancreatic islet transplantation. Keywords Type 1 diabetes . Islet transplantation . Islet niche . Biomaterial . Encapsulation Introduction Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic β cells. Treatment is optimized insulin injections with regular monitoring of blood glucose concentration. Although insulin therapy has improved quality of life for patients, many patients suffer from hypoglycemic episodes [1], have suboptimal glycemic control which increases the risk of long-term diabetes complications [2], and prevalence of coma, seizure, or death [1]. Thus, replacement of islet β-cell mass is an attractive option for patients not only to avoid insulin injection, but also to avoid complications associated with T1D. Replacement of islet β cells can be performed either D. J. Borg : E. Bonifacio (*) Preclinical Approaches to Stem Cell Therapy/Diabetes, Technische Universität Dresden, DFG-Center for Regenerative Therapies Dresden, Cluster of Excellence, Tatzberg 47/49, 01307 Dresden, Germany e-mail: ezio.bonifacio@crt-dresden.de by whole pancreas or pancreatic islet transplantation. Pancreatic islet transplantation is technically much easier for the patient, but has variable long-term success [1]. This is largely due to the intravascular hepatic transplantation site and resultant blood-mediated inflammatory reactions [3], low oxygen tension [4], and immunosuppressive drugs [5–8]. Thus, improvements that include encapsulation, co- transplantation with accessory cells or factors with or without a biomaterial, and alternative transplantation sites have been suggested to improve islet function and survival, potentially without the need for immunosuppression. We will introduce the native islet niche, report the current status of pancreatic islet co-transplantation with accessory cells/ factors, and the use of biomaterials as islet carriers or for encapsulation. With respect to encapsulation, the reader is also referred to other reviews [9–11]. Native β Cells and Their Surrounds The five endocrine cell types that comprise the islets of Langerhans work as a micro-organ to maintain glucose homeostasis. The most important cell type for this function is the insulin-producing β cell, which senses circulating nutrient levels in the blood and responds by secreting insulin [12]. β Cells rely on pancreatic and non-pancreatic environ- ments for cues that promote their function and number [12]. Within islets, a dense vascular network exists, which is essential for efficient insulin secretion and oxygen transfer. β Cells interact with the endothelial cells of the capillary network via the vascular basement membrane. Mouse β cells secrete vascular endothelial growth factor (VEGF-A) to promote vascular development, whereas the basement membrane secreted by the endothelial cells supports insulin gene expression and secretion and β-cell proliferation [13, 14]. Human islets contain a second basement membrane,