Ultrasound-triggered in situ gelation with ROS-controlled drug release for cartilage repair.

Cartilage defects are usually caused by acute trauma and chronic degeneration. However, it is still a great challenge to improve the repair of articular cartilage defects due to the limited self-regeneration capacity of such defects. Herein, a novel ROS-responsive in situ nanocomposite hydrogel loaded with kartogenin (KGN) and bone marrow-derived stem cells (BMSCs) was designed and constructed via the enzymatic reaction of fibrinogen and thrombin. Meanwhile, a ROS-responsive thioketal (TK)-based liposome was synthesized to load the chondrogenesis-inducing factor KGN, the bioenzyme thrombin and an ultrasound-sensitive agent PpIX. Under ultrasound stimulation, the TK-based liposome was destroyed, followed by in situ gelation of fibrinogen and thrombin. Moreover, sustained release of KGN was realized by regulating the ultrasound conditions. Importantly, ROS generation and KGN release within the microenvironment of the in situ fibrin hydrogel significantly promoted chondrogenic differentiation of BMSCs via the Smad5/mTOR signalling pathway and effectively improved cartilage regeneration in a rat articular cartilage defect model. Overall, the novel in situ nanocomposite hydrogel with ROS-controlled drug release has great potential for efficient cartilage repair.

Exosome-Laden Hydrogels: A Novel Cell-free Strategy for In-situ Bone Tissue Regeneration.

In-situ bone tissue regeneration, which harnesses cell external microenvironment and their regenerative potential to induce cell functions and bone reconstruction through some special properties of biomaterials, has been deeply developed. In which, hydrogel was widely applied due to its 3D network structure with high water absorption and mimicking native extracellular matrix (ECM). Additionally, exosomes can participate in a variety of physiological processes such as cell differentiation, angiogenesis and tissue repair. Therefore, a novel cell-free tissue engineering (TE) using exosome-laden hydrogels has been explored and developed for bone regeneration in recent years. However, related reviews in this field are limited. Therefore, we elaborated on the shortcomings of traditional bone tissue engineering, the challenges of exosome delivery and emphasized the advantages of exosome-laden hydrogels for in-situ bone tissue regeneration. The encapsulation strategies of hydrogel and exosomes are listed, and the research progress and prospects of bioactive hydrogel composite system for continuous delivery of exosomes for in-situ bone repair are also discussed in this review.

Finite Element Analysis of Lightning Damage Factors Based on Carbon Fiber Reinforced Polymer.

While carbon-fiber-reinforced polymers (CFRPs) are widely used in the aerospace industry, they are not able to disperse current from lightning strikes because their conductivity is relatively low compared to metallic materials. As such, the undispersed current can cause the vaporization or delamination of the composites, threatening aircraft safety. In this paper, finite element models of lightning damage to CFRPs were established using commercial finite element analysis software, Abaqus, with the user-defined subroutines USDFLD and HEAVEL. The influences of factors such as the structural geometry, laminate sequence, and intrinsic properties of CFRPs on the degree of damage to the composites are further discussed. The results showed that when a current from lightning is applied to the CFRP surface, it mainly disperses along the fiber direction in the outermost layer. As the length of the CFRP increases, the injected current has a longer residence time in the material due to the increased current exporting distance. Consequently, larger amounts of current accumulate on the surface, eventually leading to more severe damage to the CFRP. This damage can be alleviated by increasing the thickness of the CFRP, as the greater overall resistance makes the CFRP a better insulator against the imposed current. This study also found that the damaged area increased as the angle between the first two layers increased, whereas the depth of the damage decreased due to the current dispersion between the first two layers. The analysis of the electrical conductivity of the composite suggested that damage in the fiber direction will be markedly reduced if the conductivity in the vertical fiber direction increases approximately up to the conductivity of the fiber direction. Moreover, increasing the thermal conductivity along the fiber direction will accelerate the heat dissipation process after the lightning strike, but the influence of the improved thermal conductivity on the extent of the lightning damage is less significant than that of the electrical conductivity.

Silencing of lncRNA XIST impairs angiogenesis and exacerbates cerebral vascular injury after ischemic stroke.

The aim of this study was to investigate the function and regulatory mechanism of long non-coding RNA (lncRNA) X-inactive-specific transcript (XIST) in cerebral ischemic stroke (CIS). The impact of lncRNA XIST on CIS was evaluated in acute CIS patients, middle cerebral artery occlusion (MCAO) mice, and oxygen-glucose deprivation and restoration brain endothelial cells. Our results demonstrated that the expression of lncRNA XIST decreased during the early stages of CIS but then increased in the later stages in CIS patients and ischemic models in vivo and in vitro. In addition, the serum levels of lncRNA XIST negatively correlated with severity of neurological impairment of CIS patients. Further studies exhibited that lncRNA XIST regulated the expression of proangiogenic factor-integrin α5 (Itgα5) and anti-inflammation factor-Kruppel-like transcription factor 4 (KLF4) by targeting microRNA-92a (miR-92a). Silencing of lncRNA XIST impaired angiogenesis and exacerbated cerebral vascular injury following CIS, leading to larger infarcts and worse neurological deficits in transient MCAO mice. Mechanistic analysis revealed that lncRNA XIST modulated angiogenesis and alleviated cerebral vascular injury following CIS through mediating the miR-92a/Itgα5 or KLF4 axis, respectively. These data indicate that lncRNA XIST confers protection against CIS, providing a valuable target for future prevention and treatment of CIS.

Effect of pulsed millisecond current magnetic field on the proliferation of C6 rat glioma cells.

In recent years, using electromagnetic fields as a targeted therapy for tumors has become a new idea. This paper aims to study the response of rat glioma cells (C6) when the external electromagnetic field parameters change and to obtain a complete working range of magnetic field parameters. Four-day, 4-h daily millisecond magnetic field exposure experiments were performed with C6 cells. The peak values of magnetic field intensity were 260 mT, 90 mT, 19 mT and 6 mT. Each day after exposure, cell morphology and cell viability assay (MTT method) were measured. The response of C6 cells shows a significant window effect and time cumulative effect on the cell, and it is non-destructive. The working inhibited magnetic field range of magnetic field increase rate dB/dt (T/s) is [34, 119.5] and [166.75, 527.25], the magnetic field amplitude B (mT) is [6, 260], the magnetic field integral Bt (mT·s) is [0.1649, 0.8085] and the energy integral B2t (mT2·s) is [2.317, 53.328]. Our findings provide the theoretical and experimental basis for clinical applications of electromagnetic fields.