Biomaterials regulates BMSCs differentiation via mechanical microenvironment.

Bone mesenchymal stem cells (BMSCs) are crucial for bone tissue regeneration, the mechanical microenvironment of hard tissues, including bone and teeth, significantly affects the osteogenic differentiation of BMSCs. Biomaterials may mimic the microenvironment of the extracellular matrix and provide mechanical signals to regulate BMSCs differentiation via inducing the secretion of various intracellular factors. Biomaterials direct the differentiation of BMSCs via mechanical signals, including tension, compression, shear, hydrostatic pressure, stiffness, elasticity, and viscoelasticity, which can be transmitted to cells through mechanical signalling pathways. Besides, biomaterials with piezoelectric effects regulate BMSCs differentiation via indirect mechanical signals, such as, electronic signals, which are transformed from mechanical stimuli by piezoelectric biomaterials. Mechanical stimulation facilitates achieving vectored stem cell fate regulation, while understanding the underlying mechanisms remains challenging. Herein, this review summarizes the intracellular factors, including translation factors, epigenetic modifications, and miRNA level, as well as the extracellular factor, including direct and indirect mechanical signals, which regulate the osteogenic differentiation of BMSCs. Besides, this review will also give a comprehensive summary about how mechanical stimuli regulate cellular behaviours, as well as how biomaterials promote the osteogenic differentiation of BMSCs via mechanical microenvironments. The cellular behaviours and activated signal pathways will give more implications for the design of biomaterials with superior properties for bone tissue engineering. Moreover, it will also provide inspiration for the construction of bone organoids which is a useful tool for mimicking in vivo bone tissue microenvironments.

Enhanced fluorescence detection of proteins using ZnO nanowires integrated inside microfluidic chips.

Nanostructure-enhanced detection is promising for a number of applications such as early cancer diagnosis, environmental monitoring and mine safety, among which nanostructures integrated microfluidic chips offers unique advantage of ultra-low quantitative analyses. Here, dense ZnO nanowires of varied diameter and length were obtained by changing the content of polyethyleneimine (PEI) and growth time via simple hydrothermal growth in microfluidic channels for protein detection. We showed that this approach was superiorly efficient compared to the conventional hydrothermal method due to the flow-induced replenishment of nutrient and the effect of shear stress. When immobilizing FITC conjugated anti-bovine immunoglobulin G (IgG) on ZnO nanowires, the fluorescence emission was significantly amplified compared to glass substrate and ZnO seed layer. Under the different growth conditions, the most remarkable fluorescence enhancement was observed on the ZnO nanowire substrate grown for 3h with 5mM PEI in solution. It is ascribed not only to the increase of the binding surface area of proteins but also the intrinsic fluorescence enhancement of ZnO nanowires as waveguides. We further used the optimized ZnO nanowires to demonstrate multiple detection of cancer biomarkers, achieving a superior limit of detection (LOD) as low as 1pg/mL in human α-fetoprotein (AFP) assay and 100 fg/mL in carcinoembryonic antigen (CEA) assay with large dynamic range of 6-7 orders, which suggests that ZnO nanowire integrated microfluidic chips are promising for high-throughput fluorescence-based diagnostic assays.