Curr Diab Rep (2011) 11:434–444 with small clusters of dispersed rat islets. Films were then graded by the number of attached islet clusters. Laminin coatings and mildly hydrophobic polymers (e.g., low molecular weight PLGA) performed well, in addition to double layer coatings, which were comprised of PLGA on the bottom with a second material (carboxyl groups, methylesters) on top. Islet cell morphology appeared spread and ruffled and when cells were added in multiple layers, cells of all layers remained viable for 7 days [67]. The group of Mei et al. [68•] analyzed a microarrayed library of 496 different polymers, comprised of 22 different acrylate monomers in different combinations. Monomers were chosen with a range of chemical groups, crosslinking density and varying hydrophobicity and hydrophilicity to generate chemically diverse polymers. Attachment of islet cells was supported by few polymers with distinct characteristics. The findings were confirmed in another set of polymers [68•]. Further studies are required to determine whether the dispersed attached β cells are still glucose responsive in vitro and whether polymers as a transplanta- tion unit for islets could improve glycemia in diabetic animal models. Protection and Security A major drawback of islet transplantation is the immuno- suppression that is required to prevent transplant rejection. Not only does this cause undesired side effects to the immune system, the immunosuppressive drugs also have detrimental effects on islet function and survival [5–8]. Since the late 1970s, researchers have pursued encapsulat- ing both allo- and xeno-derived islets via different methods, as a means of protecting the islets and potentially eliminating the need for immunosuppression [9]. The concept of encapsulation involves separating the trans- planted cells from the host immune system by a semiper- meable, biocompatible membrane. The membrane should contain pores small enough to prevent entry of inflamma- tory cells and large proteins, such as antibodies, but large enough to allow transfer of nutrients, oxygen, and hormones [10]. To date, three types of encapsulation systems have been studied by researchers in the field. Extravascular Chambers Pioneering islet transplantation animal studies using planar or tubular diffusion chambers in the early 1980s produced variable results due to varying hormone diffusion capabil- ities of the membranes used and overgrowth of fibroblasts in the graft and/or chamber. The main advantage of these devices was the ease of graft chamber retrieval from the various extravascular transplantation sites. However, the drawback was the decrease in islet function due to fibrosis, 439 lack of immediate vascularization, and extended nutrient/ hormone diffusion time, brought about by the design of these chambers [69]. The use of smooth polyacrylonitrile- polyvinyl chloride (PAN-PVC) membranes in the 1990s markedly decreased the adhesion and fibrosis seen in these earlier studies [9]. In an isolated clinical study, as a proof of concept, patients with diabetes were transplanted with a marginal mass of allogenic islets in chambers at a subcutaneous site without immunosuppression. The chambers were biocompatible and after 2 weeks, grafts were removed and islets were still glucose responsive [70]. Research since this time has concentrated on optimizing chamber designs [71, 72], improving vascularization; either by treating with growth factors pretransplantation [73] or at the time of transplantation [74, 75] or implanting the device prior to islet insertion [76] or improving oxygen transfer [77••]. For example, a recent study showed islet function retention of allogeneic pig islets contained within a subcutaneous transplanted, oxygen-refueled macrochamber (βAir device). This device was comprised of a chamber that provided oxygen supply through a gas-permeable membrane to the alginate immobilized islets, which were immunopro- tected by a Teflon membrane (against cellular invaders) and a mannuronic acid-alginate–coated Teflon membrane (against antibody and complement penetration). They showed the device was biocompatible after 13 days with no local inflammatory or fibrotic reactions and that the islets main- tained similar insulin secretion levels when compared with levels prior to transplantation [77••]. Progress is still required for the successful translation of extravascular grafts to the clinic; specifically, accurate chamber design to reduce membrane stress and breakage [9], improvement of the graft vascularization, and a transplantation site that is minimally evasive to allow for removal to replace exhausted islets, if required [9, 10]. Intravascular Chambers Around the time of extravascular device transplantation, the notion of connecting small chambers to the host vascular system and separating islets with an immunoprotective membrane received attention [9]. These intravascular devices overcame the diffusion oxygenation and nutrition limitations due to a closer proximity to the blood [69]. The first reports to use such a system achieved normoglycemia in autologous diabetic rat [78, 79] and monkey models [79]. Further studies by these groups [80–82] and others [69] improved chamber design to decrease coagulation and demonstrated functional allogeneic [80, 81] and xenogeneic [69, 82] islet grafts, without the use of immunosuppression. However, exogenous insulin was still required [82]. A modified approach was taken by Cronin et al. [83] in a diabetic mouse model, which involved running a portion of