Infected wounds caused by persistent inflammation exhibit poor vascularization and cellular infiltration. In order to rapidly control the inflammatory effect and accelerate wound healing, it is necessary to develop a novel drug vehicle addressing the need for infected wounds. Herein, we developed a novel dual-drug delivery system with micrometer-scale alginate fibers encapsulated in instant self-assembly peptide hydrogel. Short peptides with the sequence of Nap-Gly-Phe-Phe-Lys-His (Nap-GFFKH) could self-assemble outside the microfluidic-based alginate microfibers in weak acidic solution (pH ≈ 6.0) within 5 s. The gelation condition is close to the pH environment of the human skin. We further constructed recombinant bovine basic fibroblast growth factor (FGF-2) in fibrous alginate, which was encapsulated in antibiotic-loaded peptide hydrogel. The dual-drug delivery system exhibited good mechanical property and sustained release profiles, where antibiotic could be rapidly released from the peptide hydrogel, while the growth factor could be gradually released within 7 days. Both in vitro antibacterial experiments and in vivo animal experiments confirmed that such a dual-drug delivery system has good antibacterial activity and enhances wound healing property. We suggested that the dual-drug delivery system could be potentially applied for controlled drug release in infected wound healing, drug combination for melanoma therapy, and tissue engineering.

A targeted drug delivery system based on carbon nanohorns for targeting P-glycoprotein and delivering etoposide into cells to overcome multidrug resistance.

For the first time, we have developed a microfluidic device for on-chip monitoring of suspension cell-cell communication from stimulated to recipient HL-60 cells. A deformable PDMS membrane was developed as a compressive component to perform cell entrapment and exert different modes of mechanical stimulation. The number of cells trapped by this component could be modulated by flushing excessive cells towards the device outlet. The trapped cells could be triggered to release mediators by mechanical stimulation. Sandbag microstructures were used to immobilize recipient cells at well-defined positions. These recipient cells were evoked by mediators released from mechanically stimulated cells trapped in the compressive component. Normally closed microvalves were integrated to provide continuous-flow and static environment. We studied cell-cell communication between stimulated (in compressive component) and recipient (in sandbag structures) cells. Calcium oscillations were observed in some recipient cells only when a low number of cells were stimulated. Different mechanical stimulation and flow environment were also employed to study their impact on the behavior of cell-cell communication. We observed that both the duration and intensity of intracellular calcium responses increased in persistent stimulation and decreased in flowing environment. This microdevice may open up new avenues for real-time monitoring of suspension cell-cell communication, which propagates via gap-junction independent mechanism, with multiple variables under control.

Recent studies reveal that solid tumors consist of heterogeneous cells with distinct phenotypes and functions. However, it is unclear how different subtypes of cancer cells migrate under chemotaxis. Here, we developed a microfluidic device capable of generating multiple stable gradients, culturing cells on-chip, and monitoring single cell migratory behavior. The microfluidic platform was used to study gradient-induced chemotaxis of lung cancer stem cell (LCSC) and differentiated LCSC (dLCSC) in real time. Our results showed the dynamic and differential response of both LCSC and dLCSC to chemotaxis, which was regulated by the β-catenin dependent Wnt signaling pathway. The microfluidic analysis showed that LCSC and dLCSC from the same origin behaved differently in the same external stimuli, suggesting the importance of cancer cell heterogeneity. We also observed for the first time the acceleration of both LCSC and dLCSC during chemotaxis caused by increasing local concentration in different gradients, which could only be realized through the microfluidic approach. The capability to analyze single cell chemotaxis under spatially controlled conditions provides a novel analytical platform for the study of cellular microenvironments and cancer cell metastasis.