Rapid Mining of Fast Ion Conductors via Subgraph Isomorphism Matching.

The rapidly evolving field of inorganic solid-state electrolytes (ISSEs) has been driven in recent years by advances in data-mining techniques, which facilitates the high-throughput computational screening for candidate materials in the databases. The key to the mining process is the selection of critical features that underline the similarity of a material to an existing ISSE. Unfortunately, this selection is generally subjective and frequently under debate. Here we propose a subgraph isomorphism matching method that allows an objective evaluation of the similarity between two compounds according to the topology of the local atomic environment. The matching algorithm has been applied to discover four structure types that are highly analogous to the LiTi2(PO4)3 NASICON prototype. We demonstrate that the local atomic environments similar to LiTi2(PO4)3 endow these four structures with favorable Li diffusion tunnels and ionic conductivity on par with those of the prototype. By further taking into account the electronic structure and electrochemical stability window, 13 compounds are identified to be potential ISSEs. Our findings not only offer a promising approach toward rapid mining of fast ion conductors without limitation in the compositional range but also reveal insights into the design of ISSEs according to the topology of their framework structures.

Crystal Structure Assignment for Unknown Compounds from X-ray Diffraction Patterns with Deep Learning.

Determining the structures of previously unseen compounds from experimental characterizations is a crucial part of materials science. It requires a step of searching for the structure type that conforms to the lattice of the unknown compound, which enables the pattern matching process for characterization data, such as X-ray diffraction (XRD) patterns. However, this procedure typically places a high demand on domain expertise, thus creating an obstacle for computer-driven automation. Here, we address this challenge by leveraging a deep-learning model composed of a union of convolutional residual neural networks. The accuracy of the model is demonstrated on a dataset of over 60,000 different compounds for 100 structure types, and additional categories can be integrated without the need to retrain the existing networks. We also unravel the operation of the deep-learning black box and highlight the way in which the resemblance between the unknown compound and a structure type is quantified based on both local and global characteristics in XRD patterns. This computational tool opens new avenues for automating structure analysis on materials unearthed in high-throughput experimentation.

Prevalence of radiographic parameters on CT associated with femoroacetabular impingement in a Chinese asymptomatic population.

BACKGROUND: Imaging evaluation of femoroacetabular impingement (FAI) plays a major role in early diagnosis and treatment, preventing irreversible degenerative changes in hip joints. PURPOSE: To investigate the anatomical parameters associated with FAI in a Chinese asymptomatic population by computed tomography (CT) and to evaluate the prevalence of the radiographic features of cam and pincer types in Chinese patients. MATERIAL AND METHODS: We reviewed the CT images of 470 hips in 235 Chinese patients who underwent abdominal and pelvic CT scans for reasons unrelated to hip symptoms at our hospital between February and October 2017. The following measurements were made on each hip joint: acetabular version angle (AV); anterior acetabular sector angle (AASA); posterior acetabular sector angle (PASA); the lateral center edge angle (LCE); the alpha angle (AA); and femoral head-neck offset (FHNO). RESULTS: Significant differences in all parameters were seen between men and women. Young men and elderly women showed more retroversion in our study. LCE, AA, and FHNO were all larger in men than women. The data showed 25% of female joints and 34.5% of male joints had at least one predisposing factor for FAI using measurement parameters by CT images in Chinese asymptomatic patients, and the prevalence of pincer lesion (19.1%) was larger than cam lesion (9.1%). CONCLUSION: Morphological features associated with FAI are also present in Chinese asymptomatic patients. The threshold values for abnormal parameters should be reconsidered based on gender, age, and other factors in order to improve the accuracy of diagnosis.

Periodic Mechanical Stress INDUCES Chondrocyte Proliferation and Matrix Synthesis via CaMKII-Mediated Pyk2 Signaling.

BACKGROUND/AIMS: Periodic mechanical stress can promote chondrocyte proliferation and matrix synthesis to improve the quality of tissue-engineered cartilage. Although the integrin ß1-ERK1/2 signal cascade has been implicated in periodic mechanical stress-induced mitogenic effects in chondrocytes, the precise mechanisms have not been fully established. The current study was designed to probe the roles of CaMKII and Pyk2 signaling in periodic mechanical stress-mediated chondrocyte proliferation and matrix synthesis. METHODS: Chondrocytes were subjected to periodic mechanical stress, proliferation was assessed by direct cell counting and CCK-8 assay; gene expressions were analyzed using quantitative real-time PCR, protein abundance by Western blotting. RESULTS: Mechanical stress, markedly enhanced the phosphorylation levels of Pyk2 at Tyr402 and CaMKII at Thr286. Both suppression of Pyk2 with Pyk2 inhibitor PF431396 or Pyk2 shRNA and suppression of CaMKII with CaMKII inhibitor KN-93 or CaMKII shRNA blocked periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. Additionally, either pretreatment with KN-93 or shRNA targeted to CaMKII prevented the activation of ERK1/2 and Pyk2 under conditions of periodic mechanical stress. Interestingly, in relation to periodic mechanical stress, in the context of Pyk2 inhibition with PF431396 or its targeted shRNA, only the phosphorylation levels of ERK1/2 were abrogated, while CaMKII signal activation was not affected. Moreover, the phosphorylation levels of CaMKII- Thr286 and Pyk2- Tyr402 were abolished after pretreatment with blocking antibody against integrinß1 exposed to periodic mechanical stress. CONCLUSION: Our results collectively indicate that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis through the integrinß1-CaMKII-Pyk2-ERK1/2 signaling cascade.

A novel role for integrin-linked kinase in periodic mechanical stress-mediated ERK1/2 mitogenic signaling in rat chondrocytes.

In recent years, a variety of studies have been performed to investigate the cellular responses of periodic mechanical stress on chondrocytes. Integrin ß1-mediated ERK1/2 activation was proven to be indispensable in periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. However, other signal proteins responsible for the mitogenesis of chondrocytes under periodic mechanical stress remain incompletely understood. In the current investigation, we probed the roles of integrin-linked kinase (ILK) signaling in periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. We found that upon periodic mechanical stress induction, ILK activity increased significantly. Depletion of ILK with targeted shRNA strongly inhibited periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. In addition, pretreatment with a blocking antibody against integrin ß1 resulted in a remarkable decrease in ILK activity in cells exposed to periodic mechanical stress. Furthermore, inhibition of ILK with its target shRNA significantly suppressed ERK1/2 activation in relation to periodic mechanical stress. Based on the above results, we identified ILK as a crucial regulator involved in the integrin ß1-ERK1/2 signal cascade responsible for periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis.

Integrin ß1 Gene Therapy Enhances in Vitro Creation of Tissue-Engineered Cartilage Under Periodic Mechanical Stress.

BACKGROUND/AIMS: Periodic mechanical stress activates integrin ß1-initiated signal pathways to promote chondrocyte proliferation and matrix synthesis. Integrin ß1 overexpression has been demonstrated to play important roles in improving the activities and functions of several non-chondrocytic cell types. Therefore, in the current study, we evaluated the effects of integrin ß1 up-regulation on periodic mechanical stress-induced chondrocyte proliferation, matrix synthesis and ERK1/2 phosphorylation in chondrocyte monolayer culture, and evaluated the quality of tissue-engineered cartilage constructed in vitro under periodic mechanical stress combined with integrin ß1 up-regulation. METHODS AND RESULTS: Our results revealed that under periodic mechanical stress, pre-treatment with integrin ß1-wild type vector significantly enhanced chondrocyte proliferation and matrix synthesis and promoted ERK1/2 phosphorylation in comparison to mock transfectants. Furthermore, when chondrocytes were seeded in PLGA scaffolds, more accumulated GAG and type II collagen tissue were detected after Lv-integrin ß1 transfection compared with sham controls exposed to periodic mechanical stress. In contrast, in the Lv-shRNA-integrin ß1 group, the opposite results were observed. CONCLUSION: Our findings collectively suggest that in addition to periodic mechanical stress, integrin ß1 up-regulation in chondrocytes could further improve the quality of tissue-engineered cartilage.

Changes in early serum metal ion levels and impact on liver, kidney, and immune markers following metal-on-metal total hip arthroplasty.

We retrospectively studied 32 consecutive patients (32 hips) who underwent THA with a Durom large-head, MOM articulation between January 2008 and December 2010. Of the patients who underwent THA using a Trilogy metal on polyethylene prosthesis during the same period, 32 were chosen to form the Trilogy group. 32 volunteers were chosen to form the control group. At the last follow-up, serum metal ion levels, liver and kidney function and host immunologic immune responses were evaluated. The mean Co and Cr levels in the Durom group were 4.33- and 1.95-fold higher than those in the Trilogy group. CD3+, CD4+ and CD8+ cell levels in the Durom group were significantly decreased. The INF-γ level in the Durom group was significantly higher than that in the Trilogy and control groups.

Influence of Li Content on the Topological Inhibition of Oxygen Loss in Li-Rich Cathode Materials.

Lithium-rich layer oxide cathodes are promising energy storage materials due to their high energy densities. However, the oxygen loss during cycling limits their practical applications. Here, the essential role of Li content on the topological inhibition of oxygen loss in lithium-rich cathode materials and the relationship between the migration network of oxygen ions and the transition metal (TM) component are revealed. Utilizing first-principles calculations in combination with percolation theory and Monte Carlo simulations, it is found that TM ions can effectively encage the oxidized oxygen species when the TM concentration in TM layer exceeds 5/6, which hinders the formation of a percolating oxygen migration network. This study demonstrates the significance of rational compositional design in lithium-rich cathodes for effectively suppressing irreversible oxygen release and enhancing cathode cycling performance.

Mechanochemically Robust LiCoO2 with Ultrahigh Capacity and Prolonged Cyclability.

Pushing intercalation-type cathode materials to their theoretical capacity often suffers from fragile Li-deficient frameworks and severe lattice strain, leading to mechanical failure issues within the crystal structure and fast capacity fading. This is particularly pronounced in layered oxide cathodes because the intrinsic nature of their structures is susceptible to structural degradation with excessive Li extraction, which remains unsolved yet despite attempts involving elemental doping and surface coating strategies. Herein, a mechanochemical strengthening strategy is developed through a gradient disordering structure to address these challenges and push the LiCoO2 (LCO) layered cathode approaching the capacity limit (256 mAh g-1, up to 93% of Li utilization). This innovative approach also demonstrates exceptional cyclability and rate capability, as validated in practical Ah-level pouch full cells, surpassing the current performance benchmarks. Comprehensive characterizations with multiscale X-ray, electron diffraction, and imaging techniques unveil that the gradient disordering structure notably diminishes the anisotropic lattice strain and exhibits high fatigue resistance, even under extreme delithiation states and harsh operating voltages. Consequently, this designed LCO cathode impedes the growth and propagation of particle cracks, and mitigates irreversible phase transitions. This work sheds light on promising directions toward next-generation high-energy-density battery materials through structural chemistry design.

Periodic mechanical stress stimulates the FAK mitogenic signal in rat chondrocytes through ERK1/2 activity.

BACKGROUND/AIMS: The biological effects of periodic mechanical stress on chondrocytes have been studied extensively over the past few years. However, the mechanisms underlying chondrocyte mechanosensing and signaling in response to periodic mechanical stress remain to be determined. In the current study, we examined the effects of focal adhesion kinase (FAK) signaling on periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. METHODS AND RESULTS: Periodic mechanical stress significantly induced sustained phosphorylation of FAK at Tyr(397) and Tyr(576/577). Reduction of FAK with targeted shRNA via transfection of NH2-terminal tyrosine phosphorylation-deficient FAK mutant Y397F or Y576F-Y577F abolished periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis, accompanied by attenuated ERK1/2 phosphorylation. However, activation of Src, PLCγ1 and Rac1 was not prevented upon FAK suppression. Furthermore, pretreatment with the Src-selective inhibitor, PP2, and shRNA targeted to Src or suppression of Rac1 with its selective inhibitor, NSC23766, blocked FAK phosphorylation at Tyr,(576/577) but not Tyr,(397) under periodic mechanical stress. Interestingly, FAK phosphorylation neither at Tyr(397) nor at Tyr(576/577) was affected by PLCγ1 depletion when periodic mechanical stress was applied. In addition, Tyr(397) and Tyr(576/577) phosphorylation levels were reduced upon pretreatment with a blocking antibody against integrin ß1 under conditions of periodic mechanical stress. CONCLUSION: Our findings collectively suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis through at least two pathways, integrin ß1-Src-Rac1-FAK(Tyr(576/577))-ERK1/2 and integrin ß1-FAK (Tyr(397))-ERK1/2.

Reproductive toxicity in adult male rats following intra-articular injection of cobalt-chromium nanoparticles.

BACKGROUND: Recent studies have reported that metallic nanoparticles and ions from cobalt-chromium (CoCr) alloy prostheses had potential adverse effects. However, the biological effects of CoCr nanoparticles on male reproductive function remain unclear. The objective of this study is to investigate the reproductive toxicity in adult male rats following intra-articular injection of cobalt-chromium nanoparticles. METHODS: CoCr nanoparticles were generated by a spark discharge method. Adult male rats received intra-articular injections of CoCr nanoparticles once a week at a low (20 µg/kg b.w.), medium (100 µg/kg b.w.) or high dose (500 µg/kg b.w.) for 10 consecutive weeks. The control group received intra-articular injections of physiological saline. After the final injection, all rats were held for a 7-day post-exposure period. The effects on male reproductive function were observed, including the coefficient of testicular to body weight, the epididymal sperm parameters, the concentration of metal ions in serum and testis, the activity of antioxidase and the content of lipid peroxide in the testis, and histopathological examination. RESULTS: Compared with the control group, intra-articular injection of high dose CoCr nanoparticles could significantly reduce epididymal sperm motility, viability and concentration, increase abnormal sperm rate and levels of Co and Cr ions in serum and in the testis, and induce testicular damage and pathological changes via oxidative stress. CONCLUSIONS: Intra-articular injection of high dose CoCr nanoparticles from MOM articulation may have potential reproductive toxicity in adult male rats.

Co-cultivated mesenchymal stem cells support chondrocytic differentiation of articular chondrocytes.

PURPOSE: This study investigated which of the reciprocal stimuli between articular chondrocytes (ACs) and mesenchymal stem cells (MSCs) played the more important role in enhancing cartilage matrix formation, and examined the relative importance of physical contact and soluble factors in the co-culture system. METHODS: Rat ACs and bone marrow MSCs with green fluorescent protein (GFP-BMSCs) were co-cultured in vitro with or without direct cell-cell contact at the ratio of 2:1. After co-culturing in direct cell-cell contact, ACs and GFP-BMSCs were separated by flow cytometry. The effects of different co-culture methods were analysed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. RESULTS: SOX-9, COL2 and aggrecan mRNA levels and protein expression in ACs co-cultured with direct cell-cell contact were significantly higher than in ACs co-cultured without direct cell-cell contact; and similar results were found in GFP-BMSCs. After co-culture either with or without direct cell-cell contact, mRNA levels and protein expression of SOX-9, COL2 and aggrecan in GFP-BMSCs were significantly lower than in ACs in the equivalent co-culture systems. Though the expression of chondrocyte-specific proteins in GFP-BMSCs was enhanced, the protein expression was still much lower than in ACs cultured alone. CONCLUSIONS: Reciprocal interactions exist between ACs and BMSCs in co-culture. The stimulating and supporting effects of BMSCs on ACs were more important in enhancing cartilage-matrix formation than the reciprocal effect of ACs on BMSCs. Both soluble factors and direct physical contact occur in AC/BMSC co-cultures, with physical contact playing a predominant, or at least very important role.

Closo-[B12 H12 ]2- Derivatives with Polar Groups As Promising Building Blocks in Metal-Organic Frameworks for Gas Separation.

Engineering design of metal organic frameworks (MOFs) for gas separation applications is nowadays a thriving field of investigation. Based on the recent experimental studies of dodecaborate-hybrid MOFs as potential materials to separate industry-relevant gas mixtures, we herein present a systematic theoretical study on the derivatives of the closo-dodecaborate anion [B12 H12 ]2- , which can serve as building blocks for MOFs. We discover that amino functionalization can impart a greater ability to selectively capture carbon dioxide from its mixtures with other gases such as nitrogen, ethylene and acetylene. The main advantage lies in the polarization effect induced by amino group, which favors the localization of the negative charges on the boron-cluster anion and offers a nucleophilic anchoring site to accommodate the carbon atom in carbon dioxide. This work suggests an appealing strategy of polar functionalization to optimize the molecule discrimination ability via preferential adsorption.

Imitating Architectural Mortise-Tenon Structure for Stable Ni-Rich Layered Cathodes.

Ni-rich layered oxides are the most promising cathodes for Li-ion batteries, but chemo-mechanical failures during cycling and large first-cycle capacity loss hinder their applications in high-energy batteries. Herein, by introducing spinel-like mortise-tenon structures into the layered phase of LiNi0.8 Co0.1 Mn0.1 O2 (NCM811), the adverse volume variations in cathode materials can be significantly suppressed. Meanwhile, these mortise-tenon structures play the role of the expressway for fast lithium-ion transport, which is substantiated by experiments and calculations. Moreover, the particles with mortise-tenon structures usually terminate with the most stable (003) facet. The new cathode exhibits a discharge capacity of 215 mAh g-1 at 0.1 C with an initial Coulombic efficiency of 97.5%, and capacity retention of 82.2% after 1200 cycles at 1 C. This work offers a viable lattice engineering to address the stability and low initial Coulombic efficiency of the Ni-rich layered oxides, and facilitates the implementation of Li-ion batteries with high-energy density and long durability.

The Alteration Profiles of m6A-Tagged circRNAs in the Peri-Infarct Cortex After Cerebral Ischemia in Mice.

The N6-methyladenosine (m6A) modification acts as a dynamic regulatory factor in diseases by regulating the metabolism and function of the transcriptome, especially mRNAs. However, little is known regarding the functional effects of m6A modifications on circRNAs. In this research, we established a distal middle cerebral artery occlusion (MCAO) model in adult C57BL/6J mice. The mice were divided into three groups: sham surgery, 3 days after MCAO (3d), and 7 days after MCAO (7d). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) demonstrated that the mRNA expression levels of m6A-related methyltransferases (METTL3, METTL14), demethylases (FTO, ALKBH5), and reading proteins (YTHDF1, YTHDF3) altered compared to the sham group. Furthermore, the translation level of ALKBH5 and YTHDF3 was significantly decreased in the 3d group while increased in 7d group. Methylated RNA immunoprecipitation (MeRIP) and circRNA microarray indicated 85 hypermethylated and 1621 hypomethylated circRNAs in the 3d group. In the 7d group, the methylation level increased in 57 and decreased in 66 circRNAs. Subsequently, our results were verified by MeRIP-qPCR. Bioinformatics analysis was performed to analyze the functions of differentially m6A-modified circRNAs. We found some m6A modified-circRNAs associated with cerebral infarction, providing a new direction for the molecular mechanism of stroke.

Kindlin-2 Promotes Chondrogenesis and Ameliorates IL-1beta-Induced Inflammation in Chondrocytes Cocultured with BMSCs in the Direct Contact Coculture System.

The osteoarthritis caused by trauma or inflammation is associated with severe patient morbidity and economic burden. Accumulating studies are focusing on the repair of articular cartilage defects by constructing tissue-engineered cartilage. Recent evidence suggests that optimizing the source and quality of seed cells is one of the key points of cartilage tissue engineering. In this study, we demonstrated that Kindlin-2 and its activated PI3K/AKT signaling played an essential role in promoting extracellular matrix (ECM) secretion and ameliorating IL-1beta-induced inflammation in chondrocytes cocultured with bone marrow stem cells (BMSCs). In vivo experiments revealed that coculture significantly promoted hyaline cartilage regeneration. In vitro studies further uncovered that chondrocytes cocultured with BMSCs in the direct contact coculture system upregulated Kindlin-2 expression and subsequently activated the PI3K/AKT signaling pathway, which not only increases Sox9 and Col2 expression but also restores mitochondrial membrane potential and reduces ROS levels and apoptosis under inflammatory conditions. Overall, our findings indicated that direct contact BMSC-chondrocyte coculture system could promote chondrogenesis, and identified Kindlin-2 represents a key regulator in this process.

Graph-based discovery and analysis of atomic-scale one-dimensional materials.

Recent decades have witnessed an exponential growth in the discovery of low-dimensional materials (LDMs), benefiting from our unprecedented capabilities in characterizing their structure and chemistry with the aid of advanced computational techniques. Recently, the success of two-dimensional compounds has encouraged extensive research into one-dimensional (1D) atomic chains. Here, we present a methodology for topological classification of structural blocks in bulk crystals based on graph theory, leading to the identification of exfoliable 1D atomic chains and their categorization into a variety of chemical families. A subtle interplay is revealed between the prototypical 1D structural motifs and their chemical space. Leveraging the structure graphs, we elucidate the self-passivation mechanism of 1D compounds imparted by lone electron pairs, and reveal the dependence of the electronic band gap on the cationic percolation network formed by connections between structure units. This graph-theory-based formalism could serve as a source of stimuli for the future design of LDMs.

Intercalation-driven ferroelectric-to-ferroelastic conversion in a layered hybrid perovskite crystal.

Two-dimensional (2D) organic-inorganic hybrid perovskites have attracted intense interests due to their quantum well structure and tunable excitonic properties. As an alternative to the well-studied divalent metal hybrid perovskite based on Pb2+, Sn2+ and Cu2+, the trivalent metal-based (eg. Sb3+ with ns2 outer-shell electronic configuration) hybrid perovskite with the A3M2X9 formula (A = monovalent cations, M = trivalent metal, X = halide) offer intriguing possibilities for engineering ferroic properties. Here, we synthesized 2D ferroelectric hybrid perovskite (TMA)3Sb2Cl9 with measurable in-plane and out-of-plane polarization. Interestingly, (TMA)3Sb2Cl9 can be intercalated with FeCl4 ions to form a ferroelastic and piezoelectric single crystal, (TMA)4-Fe(iii)Cl4-Sb2Cl9. Density functional theory calculations were carried out to investigate the unusual mechanism of ferroelectric-ferroelastic crossover in these crystals.

Exosomes derived from hypoxia preconditioned mesenchymal stem cells laden in a silk hydrogel promote cartilage regeneration via the miR-205-5p/PTEN/AKT pathway.

Tissue engineering has promising prospects for cartilage regeneration. However, there remains an urgent need to harvest high quality seed cells. Bone marrow mesenchymal cells (BMSCs), and in particular their exosomes, might promote the function of articular chondrocytes (ACs) via paracrine mechanisms. Furthermore, preconditioned BMSCs could provide an enhanced therapeutic effect. BMSCs naturally exist in a relatively hypoxic environment (1%-5% O2); however, they are usually cultured under higher oxygen concentrations (21% O2). Herein, we hypothesized that hypoxia preconditioned exosomes (H-Exos) could improve the quality of ACs and be more conducive to cartilage repair. In our study, we compared the effects of exosomes derived from BMSCs preconditioned with hypoxia and normoxia (N-Exos) on ACs, demonstrating that H-Exos significantly promoted the proliferation, migration, anabolism and anti-inflammation effects of ACs. Furthermore, we confirmed that hypoxia preconditioning upregulated the expression of miR-205-5p in H-Exos, suggesting that ACs were promoted via the miR-205-5p/PTEN/AKT pathway. Finally, an injectable silk fibroin (SF) hydrogel containing ACs and H-Exos (SF/ACs/H-Exos) was utilized to repair cartilage defects and effectively promote cartilage regeneration in vivo. The application of SF/ACs/H-Exos hydrogel in cartilage regeneration therefore has promising prospects. STATEMENT OF SIGNIFICANCE: Cartilage tissue engineering (CTE) has presented a promising prospect. However, the quality of seed cells is an important factor affecting the repair efficiency. Our study demonstrates for the first time that the exosomes derived from hypoxia preconditioned BMSCs (H-Exos) effectively promote the proliferation, migration and anabolism of chondrocytes and inhibit inflammation through miR-205-5p/PTEN/AKT pathway. Furthermore, we fabricated an injectable silk fibrion (SF) hydrogel to preserve and sustained release H-Exos. A complex composed of SF hydrogel, H-Exos and chondrocytes can effectively promote the regeneration of cartilage defects. Therefore, this study demonstrates that hypoxia pretreatment could optimize the therapeutic effects of BMSCs-derived exosomes, and the combination of exosomes and SF hydrogel could be a promising therapeutic method for cartilage regeneration.