Materials for Diabetes Therapeutics

This review is focused on the materials and methods used to fabricate closed-loop systems for type 1 diabetes therapy. Herein, we give a brief overview of current methods used for patient care and discuss two types of possible treatments and the materials used for these therapies–(i) artificial pancreases, comprised of insulin producing cells embedded in a polymeric biomaterial, and (ii) totally synthetic pancreases formulated by integrating continuous glucose monitors with controlled insulin release through degradable polymers and glucose-responsive polymer systems. Both the artificial and the completely synthetic pancreas have two major design requirements: the device must be both biocompatible and be permeable to small molecules and proteins, such as insulin. Several polymers and fabrication methods of artificial pancreases are discussed: microencapsulation, conformal coatings, and planar sheets. We also review the two components of a completely synthetic pancreas. Several types of glucose sensing systems (including materials used for electrochemical, optical, and chemical sensing platforms) are discussed, in addition to various polymer-based release systems (including ethylene-vinyl acetate, polyanhydrides, and phenylboronic acid containing hydrogels).Juvenile Diabetes Research Foundation International (17-2007-1063)Leona M. and Harry B. Helmsley Charitable Trust (09PG-T1D027)United States. National Institutes of Health (F32 EB011580-01

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice

By evaluating the effects of the encapsulated islet grafts with different capsule compositions and transplant sites, the authors suggest that the islet grafts with micro capsules and implanted in vascularized sites may increase clinical efficacy. Supplemental digital content is available in the text

Assembly of multilayer PSS/PAH membrane on coherent alginate/PLO microcapsule for long-term graft transplantation

Conventional alginate/poly-L-ornithine (AP) membranes used to immunoisolate foreign tissue transplants fail in long-term transplantations of immortal cell lines. We have developed a novel layer-by-layer (LbL) membrane using polystyrene sulfonate and polyallylamine hydrochloride (PSS/PAH) on top of the coherent AP membrane. Assembly of the LbL membrane was followed by electrophoresis, and the surface morphologies and structure were characterized and examined by cryo-scanning electron microscope and transmission electron microscopy. Unlike the standard AP membrane, the LbL membrane withstood the internal pressure generated by continuous cell proliferation of microencapsulated HEK-293 and Min-6 cells. The new membrane did not affect insulin secretion or diffusion by Min-6 cells. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 200