Microfluidic-Based Single-Cell Study: Current Status and Future Perspective.

Investigation of cell behavior under different environments and manual operations can give information in specific cellular processes. Among all cell-based analysis, single-cell study occupies a peculiar position, while it can avoid the interaction effect within cell groups and provide more precise information. Microfluidic devices have played an increasingly important role in the field of single-cell study owing to their advantages: high efficiency, easy operation, and low cost. In this review, the applications of polymer-based microfluidics on cell manipulation, cell treatment, and cell analysis at single-cell level are detailed summarized. Moreover, three mainly types of manufacturing methods, i.e., replication, photodefining, and soft lithography methods for polymer-based microfluidics are also discussed.

Optimized Synthesis of Biodegradable Elastomer PEGylated Poly(glycerol sebacate) and Their Biomedical Application.

Poly(glycerol sebacate) (PGS), a biodegradable elastomer, has been extensively explored in biomedical applications for its favorable mechanical properties and biocompatibility. Efforts have been made to fabricate multifunctional PGS copolymer in recent years, in particular PGS-co-PEG (poly(glycerol sebacate)-co-polyethylene glycol) polymers. However, rare research has been systematically conducted on the effect of reactant ratios on physicochemical properties and biocompatibility of PGS copolymer till now. In this study, a serial of PEGylated PGS (PEGS) with PEG content from 20% to 40% and carboxyl to hydroxyl from 0.67 to 2 were synthesized by thermal curing process. The effects of various PEGS on the mechanical strength and biological activity were further compared and optimized. The results showed that the PEGS elastomers around 20PEGS-1.0C/H and 40PEGS-1.5C/H exhibited the desirable hydrophilicity, degradation behaviors, mechanical properties and cell viability. Subsequently, the potential applications of the 20PEGS-1.0C/H and 40PEGS-1.5C/H in bone repair scaffold and vascular reconstruction were investigated and the results showed that 20PEGS-1.0C/H and 40PEGS-1.5C/H could significantly improve the mechanical strength for the calcium phosphate scaffolds and exhibited preferable molding capability for fabrication of the vascular substitute. These results confirmed that the optimized PEGS elastomers should be promising multifunctional substrates in biomedical applications.

Complement-mediated thrombotic microangiopathy as a link between endothelial damage and steroid-refractory GVHD.

Transplant-associated thrombotic microangiopathy (TA-TMA), a complication of hematopoietic cell transplant (HCT), is associated with significant morbidity and mortality. The pathophysiology and overlap of TA-TMA with other posttransplant complications such as graft-versus-host disease (GVHD) is poorly understood. We retrospectively identified cases of TA-TMA among patients with grade 3/4 gastrointestinal (GI) GVHD, reviewed intestinal biopsy specimens, and performed correlative testing of biomarkers associated with TA-TMA. TA-TMA was more common in patients with steroid-refractory GVHD compared with steroid-responsive GVHD (79.3% vs 42.1%; P = .001). Among patients surviving 100 days post-HCT, 1-year survival from day 100 was significantly better for patients who had not developed TA-TMA in the first 100 days (69.5% vs 36.7%; P < .001). Only 1 of 7 proposed TA-TMA histology criteria (mucosal hemorrhage) differed significantly based on GVHD steroid response. In multivariable modeling, steroid-refractory GVHD was a risk factor for development of TA-TMA (hazard ratio, 3.09; 95% confidence interval, 1.68-5.67; P < .001). There were no differences in complement activation at GVHD onset; however, 2 to 6 weeks later, patients with TA-TMA had higher levels of BBPlus and C5b-9, markers of alternative and terminal pathway activation (BBPlus: median, 600 vs 209.3 ng/mL; P = .0045) (C5b-9: median, 425.9 vs 258.4 ng/mL; P = .029). TA-TMA is associated with poor overall survival (OS) following HCT and may be detected early by histologic findings and may be differentiated from GVHD by measurement of alternative and terminal complement pathway activation. It is unknown whether treatment of TA-TMA will improve survival in steroid-refractory GVHD.

Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura.

Although steroids are routinely used as an adjunct to plasma exchange (PEX) therapy in the treatment of immune-mediated thrombotic thrombocytopenic purpura (iTTP), limited data regarding their efficacy or effect on ADAMTS13 biomarkers are available. We report the results of a prospective, randomized study that compared the effectiveness of prednisone or cyclosporine (CSA) as adjuncts to PEX in the treatment of iTTP. A total of 26 of the planned 72 subjects were enrolled and treated from November 2007 until February 2014 before the study was halted after a planned interim analysis. Fourteen patients were randomly assigned to the prednisone arm, and 12 to the CSA arm of the study. One patient died in each arm of the study, and 2 patients in the prednisone arm of the study failed to achieve a response and crossed over to the CSA arm, leaving 11 patients in each arm of the study evaluable for the primary end point of exacerbation. One of the 11 prednisone-treated subjects (9%) suffered an exacerbation, whereas 3 of the 11 (27%) patients in the CSA arm suffered an exacerbation. Although there was no significant difference in the exacerbation rate, suppression of the anti-ADAMTS13 antibodies and improvement in ADAMTS13 activity in the first month after stopping PEX were significantly better in the prednisone-treated subjects. Side effects were manageable and comparable in both arms of the study. These data demonstrate the superiority of prednisone over CSA as an adjunct to PEX in the suppression of the anti-ADAMTS13 antibodies and improvement in ADAMTS13 activity. This trial was registered at www.clinicaltrials.gov as #NCT00713193.