440 the femoral artery though the lumen of a silicone tube, which was filled with a Matrigel® (BD Biosciences, Franklin Lakes, NJ) solution supplemented with FGF and heparin [84] or Gelita-Spon® (Gelita Medical BV, Amsterdam, Netherlands) supplemented with nerve growth factor (NGF) [85]. In the matrigel study, islets were seeded at the time of implantation or 3 weeks after prevascularization of the chamber. Only the islets in the prevascularized chamber could improve glyce- mia of the mice [84]. Interestingly, the later study demon- strated that prevascularization of the chamber was not required when syngeneic islets were seeded with NGF. In this condition, 80% of mice achieved normoglycemia compared with 0% of mice receiving islets on the gelatin sponge alone [85]. This system takes advantage of an easily vascularized transplantation site, which allows optimal diffusion while eliminating protein deposition and coagula- tion around the graft. Microencapsulation Microencapsulation allows single or groups of islets to be immunoisolated from the host system via spherical drop- lets/beads or multilayering systems. This form of encapsu- lation has been the most intensely studied over the past three decades due to ease of production, mechanical stability, large surface-to-volume ratio, and optimal Curr Diab Rep (2011) 11:434–444 diffusion capability [10]. The size of the microspheres in early studies ranged from 600 to 800 μm; however, recent fabrication techniques have allowed 350- to 500-μm microspheres to be produced [86]. Hydrogels including alginate, poly(hydroxyethyl methacrylate-methyl methac- rylate), agarose, acrylonitrile copolymers, chitosan, and PEG are the most frequently used materials for microen- capsulation [10]. To date, the most preferred biomaterial for microencapsulation is based on alginate. Alginate consists of linear copolymers comprised of β-D-mannur- onic and α-L-guluronic acids. It is the various combina- tions of these polymers that solidify around the islet(s) in a divalent cationic solution. Various coatings (e.g., poly-L- lysine) to improve mechanical stability and improve bio- compatibility of these microcapsules have also been exten- sively studied [10]. Achievement of normoglycemia was seen in early studies with alginate-based encapsulated allogeneic [9, 87] and xenogenic [88, 89] islets transplanted into diabetic rodent models. However, attempts to upscale this system to larger animal models were inconsistently successful [90]. Soon-Shiong et al. reported both in a diabetic dog [91] and one T1D patient [92] that insulin independence could be achieved for up to 5.5 and 9 months, respectively, by transplantation of encapsulated allogeneic islets and treat- ment with cyclosporine. However, others reported an Fig. 1 Biomaterial carrier for islet transplantation. An optimal biomaterial for human islet transplantation would be one with large pore sizes to accommodate islets, as well as providing the possibility to be biofunctionalized with growth factors and potentially immuno- suppressive drugs, and with adhesion molecules so that accessory cells can be localized and with enzyme degradation sites for eventual degradation, allowing a functional revascu- larized islet micro-organ to remain at the transplantation site. (Adapted from Lutolf and Hubbell [98].)