Corrigendum to "Development of methods for detecting the fate of mesenchymal stem cells regulated by bone bioactive materials" [Bioact. Mater. 6(3) (2021) 613-626].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.08.035.].

Metabolomics analysis of the potential toxicological mechanisms of diquat dibromide herbicide in adult zebrafish (Danio rerio) liver.

Although diquat is a widely used water-soluble herbicide in the world, its sublethal adverse effects to fish have not been well characterised. In this study, histopathological examination and biochemical assays were applied to assess hepatotoxicity and combined with gas chromatography-mass spectrometry (GC-MS)-based metabolomics analysis to reveal overall metabolic mechanisms in the liver of zebrafish (Danio rerio) after diquat exposure at concentrations of 0.34 and 1.69 mg·L-1 for 21 days. Results indicated that 1.69 mg·L-1 diquat exposure caused cellular vacuolisation and degeneration with nuclear abnormality and led to the disturbance of antioxidative system and dysfunction in the liver. No evident pathological injury was detected, and changes in liver biochemistry were not obvious in the fish exposed to 0.34 mg·L-1 diquat. Multivariate statistical analysis revealed differences between profiles obtained by GC-MS spectrometry from control and two treatment groups. A total of 17 and 22 metabolites belonging to different classes were identified following exposure to 0.34 and 1.69 mg·L-1 diquat, respectively. The metabolic changes in the liver of zebrafish are mainly manifested as inhibition of energy metabolism, disorders of amino acid metabolism and reduction of antioxidant capacity caused by 1.69 mg·L-1 diquat exposure. The energy metabolism of zebrafish exposed to 0.34 mg·L-1 diquat was more inclined to rely on anaerobic glycolysis than that of normal zebrafish, and interference effects on lipid metabolism were observed. The metabolomics approach provided an innovative perspective to explore possible hepatic damages on fish induced by diquat as a basis for further research.

Bilayered scaffold with 3D printed stiff subchondral bony compartment to provide constant mechanical support for long-term cartilage regeneration.

BACKGROUND/OBJECTIVE: We seek to figure out the effect of stable and powerful mechanical microenvironment provided by Ti alloy as a part of subchondral bone scaffold on long-term cartilage regeneration.Methods: we developed a bilayered osteochondral scaffold based on the assumption that a stiff subchondral bony compartment would provide stable mechanical support for cartilage regeneration and enhance subchondral bone regeneration. The subchondral bony compartment was prepared from 3D printed Ti alloy, and the cartilage compartment was created from a freeze-dried collagen sponge, which was reinforced by poly-lactic-co-glycolic acid (PLGA). RESULTS: In vitro evaluations confirmed the biocompatibility of the scaffold materials, while in vivo evaluations demonstrated that the mechanical support provided by 3D printed Ti alloy layer plays an important role in the long-term regeneration of cartilage by accelerating osteochondral formation and its integration with the adjacent host tissue in osteochondral defect model at rabbit femoral trochlea after 24 weeks. CONCLUSION: Mechanical support provided by 3D printing Ti alloy promotes cartilage regeneration by promoting subchondral bone regeneration and providing mechanical support platform for cartilage synergistically. TRANSLATIONAL POTENTIAL STATEMENT: The raw materials used in our double-layer osteochondral scaffolds are all FDA approved materials for clinical use. 3D printed titanium alloy scaffolds can promote bone regeneration and provide mechanical support for cartilage regeneration, which is very suitable for clinical scenes of osteochondral defects. In fact, we are conducting clinical trials based on our scaffolds. We believe that in the near future, the scaffold we designed and developed can be formally applied in clinical practice.

Dual directions to address the problem of aseptic loosening via electrospun PLGA @ aspirin nanofiber coatings on titanium.

Peri-implant aseptic inflammation and osteolysis can cause aseptic loosening, leading to the failure of implants. Therefore, aseptic loosening of orthopedic implants remains an imminent problem for the development of durable and effective implants. In this work, a common anti-inflammatory drug (aspirin, ASA) was loaded in poly(lactic-co-glycolic acid) (PLGA) to construct nanofiber coatings on titanium (Ti) via electrospinning. The adhesion of the nanofiber coatings to Ti was ensured by polydopamine (PDA) modification. A stable and sustainable release of aspirin from the nanofiber coatings could last up to 60 days. Such electrospun PLGA@ASA nanofiber coatings could promote proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) as well as inhibit M1 polarization and RANKL-induced osteoclast differentiation of macrophages in vitro. These results indicated that this facile formulation of the PLGA@ASA nanofiber coatings for long-term drug release could be expected to address the problem of aseptic loosening effectively in dual directions of both anti-inflammation and improving osseointegration simultaneously. Notably, the in vivo experiments demonstrated that PLGA@ASA nanofiber coatings did promote osseointegration ability of Ti implants significantly, even in challenging condition with wear particles, and also effectively inhibited Ti particle induced osteolysis around the implants. This work indicates a promising way for the development of durable and effective implants by using PLGA@ASA-PDA-Ti to address the problem of aseptic loosening in dual directions.

3D Printing of Conductive Tissue Engineering Scaffolds Containing Polypyrrole Nanoparticles with Different Morphologies and Concentrations.

Inspired by electrically active tissues, conductive materials have been extensively developed for electrically active tissue engineering scaffolds. In addition to excellent conductivity, nanocomposite conductive materials can also provide nanoscale structure similar to the natural extracellular microenvironment. Recently, the combination of three-dimensional (3D) printing and nanotechnology has opened up a new era of conductive tissue engineering scaffolds exhibiting optimized properties and multifunctionality. Furthermore, in the case of two-dimensional (2D) conductive film scaffolds such as periosteum, nerve membrane, skin repair, etc., the traditional preparation process, such as solvent casting, produces 2D films with defects of unequal bubbles and thickness frequently. In this study, poly-l-lactide (PLLA) conductive scaffolds incorporated with polypyrrole (PPy) nanoparticles, which have multiscale structure similar to natural tissue, were prepared by combining extrusion-based low-temperature deposition 3D printing with freeze-drying. Furthermore, we creatively integrated the advantages of 3D printing and solvent casting and successfully developed a 2D conductive film scaffold with no bubbles, uniform thickness, and good structural stability. Subsequently, the effects of concentration and morphology of PPy nanoparticles on electrical properties and mechanical properties of 3D conductive scaffolds and 2D conductive films scaffolds have been studied, which provided a new idea for the design of both 2D and 3D electroactive tissue engineering scaffolds.

Three-Dimensional Printing and Injectable Conductive Hydrogels for Tissue Engineering Application.

The goal of tissue engineering scaffolds is to simulate the physiological microenvironment, in which the electrical microenvironment is an important part. Hydrogel is an ideal material for tissue engineering scaffolds because of its soft, porous, water-bearing, and other extracellular matrix-like properties. However, the hydrogel matrix is usually not conductive and can hinder the communication of electrical signals between cells, which promotes researchers' attention to conductive hydrogels. Conductive hydrogels can promote the communication of electrical signals between cells and simulate the physiological microenvironment of electroactive tissues. Hydrogel formation is an important step for the application of hydrogels in tissue engineering. In situ forming of injectable hydrogels and customized forming of three-dimensional (3D) printing hydrogels represent two most potential advanced forming processes, respectively. In this review, we discuss (i) the classification, properties, and advantages of conductive hydrogels, (ii) the latest development of conductive hydrogels applied in myocardial, nerve, and bone tissue engineering, (iii) advanced forming processes, including injectable conductive hydrogels in situ and customized 3D printed conductive hydrogels, (iv) the challenges and opportunities of conductive hydrogels for tissue engineering. Impact Statement Biomimetic construction of electro-microenvironment is a challenge of tissue engineering. The development of conductive hydrogels provides possibility for the construction of biomimetic electro-microenvironment. However, the importance of conductive hydrogels in tissue engineering has not received enough attention so far. Herein, various conductive hydrogels and their tissue engineering applications are systematically reviewed. Two potential methods of conductive hydrogel forming, in situ forming of injectable conductive hydrogels and customized forming of three-dimensional printing conductive hydrogels, are introduced. The current challenges and future development directions of conductive hydrogels are comprehensively overviewed. This review provides a guideline for tissue engineering applications of conductive hydrogels.

Langmuir-Blodgett self-assembly of ultrathin graphene quantum dot films with modulated optical properties.

Multiple-color-emissive graphene quantum dots (GQDs) have great potential in diverse applications such as bioimaging, light emission, and photocatalysis. Growing interest in GQDs is largely focused on their macro-scale aggregations that could inherit the unique properties of individual dots. However, the lack of advanced fabrication methods limits the practical applications of GQDs. Here, we employed a Langmuir-Blodgett (LB) technique to fabricate ultrathin, high-quality GQD aggregated films with well-modulated optical properties in a wide range of wavelengths. Through the combination of a bottom-up synthesis of GQDs and the LB assembly method, uniform, closely packed, and ultra-thin GQD films can be self-assembled with a well-controlled thickness on different substrates. The photoluminescence (PL) spectra of ultra-thin GQD films have an obvious red-shift compared with isolated GQD solution. We then elucidate remarkably strong energy transfer in self-assembled GQDs. Furthermore, the ultra-thin GQD films exhibit a clear excitation-dependent PL that could almost cover the entire visible light. This convenient self-assembly method and systematic optical and physical studies of ultra-thin GQD films may provide a new direction for developing low-cost, GQD film-based light-emitting devices.