The encapsulation of mammalian cells within the bulk material of microfluidic channels may be beneficial for applications ranging from tissue engineering to cell-based diagnostic assays. In this work, we present a technique for fabricating microfluidic channels from cell-laden agarose hydrogels. Using standard soft lithographic techniques, molten agarose was molded against a SU-8 patterned silicon wafer. To generate sealed and water-tight microfluidic channels, the surface of the molded agarose was heated at 71 degrees C for 3 s and sealed to another surface-heated slab of agarose. Channels of different dimensions were generated and it was shown that agarose, though highly porous, is a suitable material for performing microfluidics. Cells embedded within the microfluidic molds were well distributed and media pumped through the channels allowed the exchange of nutrients and waste products. While most cells were found to be viable upon initial device fabrication, only those cells near the microfluidic channels remained viable after 3 days, demonstrating the importance of a perfused network of microchannels for delivering nutrients and oxygen to maintain cell viability in large hydrogels. Further development of this technique may lead to the generation of biomimetic synthetic vasculature for tissue engineering, diagnostics, and drug screening applications.
In operando XAS investigation on FeCoNi-based thin film unravels that Fe3+-assisted water dissociation promotes the formation of Co2+–μ-H–Ni3+ species, and the conductive character of Co2+Ni3+-oxide matrix facilitates the coupling of adjacent [Fe4+O/Fe3+–O˙] motifs.
In human systems, reactive oxygen species (ROS) significantly affect different physiological activities and play critical roles in diverse living processes. It is widely known that excessive ROS generation in inflammatory tissues can further deteriorate the localized tissue injury and cause chronic diseases. Though promising for reducing ROS levels, many antioxidant molecules and natural enzymes suffer from abundant intrinsic limitations. Recently, a series of biocatalytic or antioxidant nanostructures have been designed with distinctive ROS scavenging capabilities, which show promising activities to overcome these kernel challenges. In this timely review, the most recent advances in engineering biocatalytic and antioxidant nanostructures for ROS scavenging are summarized. First, the ROS scavenging principles and corresponding methods for testing various enzymatic activities are carefully concluded. Subsequently, the rationally designed nanostructures with high ROS scavenging efficiencies are comprehensively discussed, especially on the catalytic activities, mechanisms, and structure‐function relationships. After that, the representative applications of these ROS scavenging nanostructures for diverse biotherapeutics are summarized in detail. At last, the primary challenges and future perspectives in this emerging research frontier have also been outlined. It is believed that this progress review will offer a cutting‐edge understanding and guidance to engineering future high‐performance ROS scavenging nanostructures for broad biotherapeutic applications.
Dendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1 TERT patients, DCV treatment significantly prolonged OS (p < 0.01) and PFS (p = 0.03) and increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment. Therefore, IDH1TERT and low B7-H4 expression identified subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy.
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