BackgroundDeveloping cartilage constructed with the appropriate matrix composition and persistent chondrogenesis remains an enduring challenge in cartilage defects. Cartilage progenitor cell (CPC)-based tissue engineering has attracted recent attention because of its strong chondrogenic differentiation capacity. However, due to the lack of a suitable chondrogenic niche, the clinical application of CPC-regenerated cartilage in the subcutaneous environment remains a challenge. In this study, exosomes derived from chondrocytes (CC-Exos) were used to provide the CPC constructs with a cartilage signal in subcutaneous environments for efficient ectopic cartilage regeneration.MethodsRabbit CPC-alginate constructs were prepared and implanted subcutaneously in nude mice. CC-Exos were injected into the constructs at the same dose (30 μg exosomes per 100 μL injection) after surgery and thereafter weekly for a period of 12 weeks. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) were used as the positive control. The mice in the negative control were administered with the same volume of PBS. At 4 and 12 weeks after implantation, the potential of CC-Exos and BMSC-Exos to promote chondrogenesis and stability of cartilage tissue in a subcutaneous environment were analyzed by histology, immunostaining, and protein analysis. The influences of BMSC-Exos and CC-Exos on chondrogenesis and angiogenic characteristics in vitro were assessed via coculturing with CPCs and human umbilical vein endothelial cells.ResultsThe CC-Exos injection increased collagen deposition and minimized vascular ingrowth in engineered constructs, which efficiently and reproducibly developed into cartilage. The generated cartilage was phenotypically stable with minimal hypertrophy and vessel ingrowth up to 12 weeks, while the cartilage formed with BMSC-Exos was characterized by hypertrophic differentiation accompanied by vascular ingrowth. In vitro experiments indicated that CC-Exos stimulated CPCs proliferation and increased expression of chondrogenesis markers while inhibiting angiogenesis.ConclusionsThese findings suggest that the novel CC-Exos provides the preferable niche in directing stable ectopic chondrogenesis of CPCs. The use of CC-Exos may represent an off-the-shelf and cell-free therapeutic approach for promoting cartilage regeneration in the subcutaneous environment.

Background Bone marrow-derived stem cells (BMSCs) and chondrocytes have been reported to present “dedifferentiation” and “phenotypic loss” during the chondrogenic differentiation process in cartilage tissue engineering, and cartilage progenitor cells (CPCs) are novel seeding cells for cartilage tissue engineering. In our previous study, cartilage progenitor cells from different subtypes of cartilage tissue were isolated and identified in vitro, but the study on in vivo chondrogenic characteristics of cartilage progenitor cells remained rarely. In the current study, we explored the feasibility of combining cartilage progenitor cells with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to produce tissue-engineered cartilage and compared the proliferation ability and chondrogenic characteristics of cartilage progenitor cells with those of bone marrow-derived stem cells and chondrocytes. Methods These three cells combined with PHBV were cultured in vitro for 1 week without chondrogenic induction and then transplanted subcutaneously into nude mice for 6 weeks. The cell-PHBV constructs were evaluated by gross observation, histological staining, glycosaminoglycan content measurement, biomechanical analysis and RT-PCR. Results The chondrocyte-PHBV constructs and CPC-PHBV constructs became an ivory-whitish cartilage-like tissue, while the BMSC-PHBV constructs became vascularized 6 weeks after the subcutaneous implantation. Histological examination showed that many typical cartilage structures were present in the chondrocyte group, some typical cartilage structures were observed in the CPC group, while no typical cartilage structures were observed in the BMSC group. Conclusions Cartilage progenitor cells may undergo chondrogenesis without chondrogenic induction and are better at chondrogenesis than BMSCs but worse than chondrocytes in the application of cartilage tissue engineering.

This study, for the first time, rendered crab shell activated biochar modified by potassium hydroxide (KOH) impregnation (CSAB), revealing a new potential application in the removal of diesel oil from oily wastewater. The structural characteristics of crab shell biochar (CSB) and CSAB were investigated by SEM, and the crystal structure and optical properties of as-prepared samples were analyzed using XRD and FTIR. Results showed that CSAB had stratified surface structure morphology, abundant functional groups, and that its high specific surface area could reach up to 2441 m2/g, which was about eight times larger than that of untreated CSB (307 m2/g). An adsorption isotherm study indicated that the actual adsorption process both of CSAB and CSB were found to fit better with the Freundlich equation. Moreover, chemical interaction controlled the adsorption kinetics efficiency while the adsorption equilibrium capacity was 93.9 mg/g. Due to its highly developed pore structure, unique surface characteristics, and effective adsorption performance, this low-cost activated carbon had the potential to serve as an efficient adsorbent for water pollution purification.

CSC may become an ideal seeding cell in cartilage tissue engineering, owing to its stemness and chondrogenic characteristics.

Cartilage tissue engineering is a promising option for repairing cartilage defects, although harvesting a large number of seeding cells remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles (EVs) may play a major role in cell-cell and tissue-tissue communication. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived EVs on CSPCs proliferation and differentiation. The characteristics of ADSCs-derived EVs were identified, and proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. SEM, histological staining, biochemical and biomechanical analysis was performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture. The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40-1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induce CSPCs to produce significantly more cartilage matrix and proteoglycan. In conclusion, hypoxic ADSCsderived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N-protein) increases early in body fluids during infection and has recently been identified as a direct inducer for lung injury. However, the signal mechanism of N-protein in the lung inflammatory response remains poorly understood. The goal of this study was to determine whether RAGE (receptor for advanced glycation endproducts) participated in N-protein–induced acute lung injury. The binding between N-protein and RAGE was examined via assays for protein–protein interaction. To determine the signaling mechanism in vitro , cells were treated with recombinant N-protein and assayed for the activation of the RAGE/MAPK (mitogen-activated protein kinase)/NF-ĸB pathway. RAGE deficiency mice and antagonist were used to study N-protein–induced acute lung injury in vivo . Binding between N-protein and RAGE was confirmed via flow cytometry–based binding assay, surface plasmon resonance, and ELISA. Pull-down and coimmunoprecipitation assays revealed that N-protein bound RAGE via both N-terminal and C-terminal domains. In vitro , N-protein activated the RAGE-ERK1/2–NF-ĸB signaling pathway and induced a proinflammatory response. RAGE deficiency subdued N-protein–induced proinflammatory signaling and response. In vivo , RAGE was upregulated in the BAL and lung tissue after recombinant N-protein insult. RAGE deficiency and small molecule antagonist partially protected mice from N-protein–induced acute lung injury. Our study demonstrated that RAGE is a receptor for N-protein. RAGE is partially responsible for N-protein–induced acute lung injury and has the potential to become a therapeutic target for treating coronavirus disease.

Repair of cartilage defects remains a challenge for surgeons, owing to its poor self‑repairing capacity. Cartilage tissue engineering, particularly marrow stem cell‑based cartilage regeneration, provides a promising option for the regeneration of damaged cartilage. Although producing tissue‑engineered cartilage from marrow stem cells appeared to be a feasible method, constructing certain sub‑types of cartilage, including elastic cartilage, remains difficult. Therefore, the present study explored the feasibility of constructing elastic cartilage by culturing bone marrow‑derived stem cells (BMSCs) in the supernatant of elastic cartilage cells to generate elastic cartilage. The elastic cartilage cells were obtained from the auricle cartilage of a newborn pig, and BMSCs were isolated from pig bone marrow aspirate. The supernatant of the chondrocytes was collected and then used to the culture BMSCs. At various time‑points, the differentiation of BMSCs was evaluated by gross view, histological examination and quantitative polymerase chain reaction. BMSCs changed from spindle‑shaped cells into polygonal cells with increasing culture time. The expression of collagen II and elastin was observed in the cells cultured in the supernatant of elastic chondrocytes, while no expression was observed in the control cells. Furthermore, the expression of collagen I and collagen X was downregulated in the cells cultured in the supernatant of elastic cartilage cells. The supernatant of elastic cartilage cells promoted the differentiation of BMSCs into elastic cartilage cells, which may be a promising method for constructing certain sub‑types of tissue‑engineered cartilage.

Deep-red (DR) and near-infrared (NIR) luminogens have witnessed powerful applications in various aspects in recent decades. However, their inevitably complicated structures not only bring tedious and time-consuming synthesis, but also lead to inherent difficult in crystallization which hinder the understanding of structure-emission relationship. Polymorphism represents an ingenious strategy for revealing unambiguous structure-emission relationships. Therefore, designing simple molecules to construct DR and NIR polymorphic emission is challenging yet highly desirable. Herein, multiple DR and NIR emission ranges from 624 to 742 nm is achieved in polymorphisms of an extremely simple π-conjugated luminogen. Multiple packing modes are simultaneously integrated into this compound. Its unique packing-dependent emission facilitates the establishment of clear packing-emission relationship. Increased intermolecular exciton coupling between adjacent molecules leads to gradually red-shifted emission from orange to DR and finally to NIR. The aggregation-induced emission feature of the molecule renders the bulk crystals with visible crystal-to-crystal polymorphic transformation under external stimuli. This work not only breaks the limitations of the research of organic polymorphism materials with NIR emission, but also provides a reliable strategy to reveal the influence of molecular packing on NIR emission.