A cure for type 1 diabetes (T1D) would help millions of people worldwide, but remains elusive thus far. Tolerogenic vaccines and beta cell replacement therapy are complementary therapies that seek to address aberrant T1D autoimmune attack and subsequent beta cell loss. However, both approaches require some form of systematic immunosuppression, imparting risks to the patient. Biomaterials-based tools enable localized and targeted immunomodulation, and biomaterial properties can be designed and combined with immunomodulatory agents to locally instruct specific immune responses. In this Review, we discuss immunomodulatory biomaterial platforms for the development of T1D tolerogenic vaccines and beta cell replacement devices. We investigate nano-and microparticles for the delivery of tolerogenic agents and autoantigens, and as artificial antigen presenting cells, and highlight how bulk biomaterials can be used to provide immune tolerance. We examine biomaterials for drug delivery and as immunoisolation devices for cell therapy and islet transplantation, and explore synergies with other fields for the development of new T1D treatment strategies.

We report on enhancement-mode ZnO-based field-effect transistors that utilize an acceptor-doped channel. In particular, the active channel is polycrystalline ZnO doped with Mg, to increase the band gap, and P, to decrease the electron carrier concentration. Devices are realized that display an on/off ratio of 10 3 and a channel mobility on the order of 5 cm 2 /V s. HfO 2 serves as the gate dielectric. Capacitance-voltage properties measured across the gate indicate that the ZnO channel is n type. The use of acceptor doping improves the control of the initial channel conductance while having a minimal impact on channel mobility relative to undoped ZnO polycrystalline channels.

Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC.Reduction of the repressive epigenetic modification H3K27me2/3 correlates with PCa aggressiveness, while corresponding demethylases JMJD3/UTX are overexpressed in PCa. We found that JMJD3/UTX inhibitor GSK-J4 reduced more efficiently proliferation of AR-ΔLBD cells (CRPC model) compared with isogenic AR-WT cells. Inhibition of JMJD3/UTX protects demethylation of H3K27Me2/3, thus reducing levels of H3k27Me1. We observed that the reduction dynamics of H3K27Me1 was faster and achieved at lower inhibitor concentrations in AR-ΔLBD cells, suggesting that inhibition of JMJD3/UTX diminished proliferation of these cells by hindering AR-driven transcription. In addition, we observed synergy between GSK-J4 and Cabazitaxel, a taxane derivative that is approved for CRPC treatment. Collectively, our results point at the H3K27 demethylation pathway as a new potential therapeutic target in CRPC patients.