Incrementally Adapting Pretrained Model Using Network Prior for Multi-Focus Image Fusion.

Multi-focus image fusion can fuse the clear parts of two or more source images captured at the same scene with different focal lengths into an all-in-focus image. On the one hand, previous supervised learning-based multi-focus image fusion methods relying on synthetic datasets have a clear distribution shift with real scenarios. On the other hand, unsupervised learning-based multi-focus image fusion methods can well adapt to the observed images but lack the general knowledge of defocus blur that can be learned from paired data. To avoid the problems of existing methods, this paper presents a novel multi-focus image fusion model by considering both the general knowledge brought by the supervised pretrained backbone and the extrinsic priors optimized on specific testing sample to improve the performance of image fusion. To be specific, the Incremental Network Prior Adaptation (INPA) framework is proposed to incrementally integrate features extracted from the pretrained strong baselines into a tiny prior network (6.9% parameters of the backbone network) to boost the performance for test samples. We evaluate our method on both synthetic and real-world public datasets (Lytro, MFI-WHU, and Real-MFF) and show that our method outperforms existing supervised learning-based methods and unsupervised learning based methods.

Sustained free chlorine-releasing polydimethylsiloxane/Ca(ClO)2 materials with long-lasting disinfection efficacy.

A novel sustained chlorine-releasing polydimethylsiloxane/Ca(ClO)2 (PDMS/Ca(ClO)2) material was fabricated by encapsulating Ca(ClO)2 in a PDMS matrix due to its high hydrophobicity and high chemical stability, which showed immediate-responsive and long-lasting antibacterial capabilities in aqueous conditions. Free chlorine could be released from the PDMS/Ca(ClO)2 after immersion in water for 2 min and could also be sustainedly released for 2 weeks, while the released concentration is negatively related to the duration time and positively with the initial Ca(ClO)2 contents. Additionally, Ca(ClO)2 powder as a filler significantly affects the crosslinking and pore size of PDMS. The PDMS/Ca(ClO)2 materials exhibited enduring antibacterial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in both planktonic and multispecies-biofilm status. It is expected that this PDMS/Ca(ClO)2 material and its similar composite would be promising candidates for wide sustainable disinfection applications in biomedical and industrial fields.

Carnitine functions as an enhancer of NRF2 to inhibit osteoclastogenesis via regulating macrophage polarization in osteoporosis.

Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis.

pH-responsive on-demand release of eugenol from metal-organic frameworks for synergistic bacterial killing.

Bacterial infections are a big challenge in clinical treatment, making it urgent to develop innovative antibacterial systems and therapies to combat bacterial infections. In this study, we developed a novel MOF-based synergistic antibacterial system (Eu@B-UiO-66/Zn) by loading a natural antibacterial substance (eugenol) with hierarchically porous MOF B-UiO-66 as a carrier and further complexing it with divalent zinc ions. Results indicate that the system achieved a controlled release of eugenol under pH responsive stimulation, with the complexation ability of eugenol and Zn2+ ions as a switch. Due to the destruction of a coordination bond between eugenol and Zn2+ ions by an acidic medium, the release of eugenol loaded in Eu@B-UiO-66/Zn reached 80% at pH 5.8, which was significantly higher than that under pH 8.0 (51%). Moreover, the inhibitory effect of Eu@B-UiO-66/Zn against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) after 24 h was 96.4% and 99.7%, respectively, owing to the synergistic antibacterial effect of eugenol and Zn2+ ions, which was significantly stronger than free eugenol and Eu@B-UiO-66. We hope that this strategy for constructing responsive MOF-based antibacterial carriers could have potential possibilities for the application of MOF materials in antibacterial fields.

Selective recycling of lithium from spent LiNixCoyMn1-x-yO2 cathode via constructing a synergistic leaching environment.

The global response to lithium scarcity is overstretched, and it is imperative to explore a green process to sustainably and selectively recover lithium from spent lithium-ion battery (LIB) cathodes. This work investigates the distinct leaching behaviors between lithium and transition metals in pure formic acid and the auxiliary effect of acetic acid as a solvent in the leaching reaction. A formic acid-acetic acid (FA-AA) synergistic system was constructed to selectively recycle 96.81% of lithium from spent LIB cathodes by regulating the conditions of the reaction environment to inhibit the leaching of non-target metals. Meanwhile, the transition metals generate carboxylate precipitates enriched in the leaching residue. The inhibition mechanism of manganese leaching by acetic acid and the leaching behavior of nickel or cobalt being precipitated after release was revealed by characterizations such as XPS, SEM, and FTIR. After the reaction, 90.50% of the acid can be recycled by distillation, and small amounts of the residual Li-containing concentrated solution are converted to battery-grade lithium carbonate by roasting and washing (91.62% recovery rate). This recycling process possesses four significant advantages: i) no additional chemicals are required, ii) the lithium sinking step is eliminated, iii) no waste liquid is discharged, and iv) there is the potential for profitability. Overall, this study provides a novel approach to the waste management technology of lithium batteries and sustainable recycling of lithium resources.

Nitisinone attenuates cartilage degeneration and subchondral osteoclastogenesis in osteoarthritis and concomitantly inhibits the cGAS/STING/NF-κB pathway.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration and subchondral bone remodelling. Currently, conservative treatment strategies cannot effectively alleviate the progression of OA. In this study, we used computer network analysis to show that Nitisinone (NTBC) is closely related to extracellular matrix degradation in OA and mainly interferes with the TNF-α signaling pathway. NTBC is an orphan drug used to treat hereditary type I tyrosinemia by altering phenylalanine/tyrosine metabolic flow. In this study, we found that NTBC effectively reduced chondrocyte inflammation and extracellular matrix degradation induced by TNF-α. Mechanistically, NTBC inhibited the cGAS/STING signaling pathway and reduced activation of the STING-dependent NF-κB pathway to alleviate inflammation. In addition, NTBC inhibited osteoclastogenesis and delayed the occurrence of subchondral bone remodelling. In mice with ACLT-induced osteoarthritis, intra-articular injection of NTBC significantly reduced cartilage degradation and subchondral bone remodelling. NTBC showed impressive therapeutic efficacy as a potential pharmaceutical intervention for the treatment of OA.

Preparation of amino-modified carbon quantum dots-ZnO/cellulose nanofiber multifunctional hydrogel: Enhanced adsorption synergistic photoreduction and reversible fluorescence response visual recognition of Cr(VI).

This work innovatively used cellulose nanofibers as a photocatalyst carrier, which could recycle nano-photocatalysts and minimize nanoparticle aggregation. The morphology, structures, chemical composition, optical-electronic properties and photocatalytic performance of amino-modified carbon quantum dots-ZnO/cellulose nanofiber (N-CQDs-ZnO/CNF: ZCH-2) hydrogel were characterized by SEM, TEM, BET, EDS, XRD, FTIR, UV-vis, XPS, PL and other techniques. The mechanism of Cr(VI) adsorption synergistic photoreduction by ZCH-2 was discussed in detail. The results showed that the prepared ZCH-2 had excellent removal performance for Cr(VI). After 120 min of adsorption and 40 min of photoreduction, the removal efficiency of Cr(VI) was 98.9 %. Compared with ZnO/CNF hydrogel, the adsorption performance of ZCH-2 increased by 268 % and the photoreduction performance increased by 116 %. The adsorption of Cr(VI) by ZCH-2 was controlled by electrostatic attraction and chemical adsorption. The photoreduction kinetic constant of ZCH-2 was 0.106 min-1, which was 8.9 times that of ZnO/CNF hydrogel. The N-CQDs in ZCH-2 could form N-CQDs-metal complexes with Cr(VI), resulting in fluorescence quenching, so Cr(VI) could be visually identified by fluorescence changes. This study provides a new idea for the design and optimization of a new multifunctional hydrogel with efficient adsorption-photoreduction-fluorescence recognition.

Macrophage migration inhibitory factor (MIF) promotes intervertebral disc degeneration through the NF-κB pathway, and the MIF inhibitor CPSI-1306 alleviates intervertebral disc degeneration in a mouse model.

Lumbar intervertebral disc degeneration(IDD) is a prevalent inflammatory disease caused by many proinflammatory factors, such as TNF and IL-1ß. Migration inhibitory factor (MIF) is an upstream inflammatory factor widely expressed in vivo that is associated with a variety of inflammatory diseases or malignant tumors and has potential therapeutic value in many diseases. We explored the role of MIF in intervertebral disc degeneration by regulating the content of exogenous MIF or the expression of MIF in cells. Upon inducing degeneration of nucleus pulposus (NP) cells with IL-1ß, we found that the increase in intracellular and exogenous MIF promoted the catabolism induced by proinflammatory factors in NP cells, while silencing of the MIF gene alleviated the degeneration to some extent. In a mouse model, the intervertebral disc degeneration of MIF-KO mice was significantly less than that of wild-type mice. To explore the treatment of intervertebral disc degeneration, we selected the small-molecular MIF inhibitor CPSI-1306. CPSI-1306 had a therapeutic effect on intervertebral disc degeneration in the mouse model. In summary, we believe that MIF plays an important role in intervertebral disc degeneration and is a potential therapeutic target for the treatment of intervertebral disc degeneration.

A novel thin single-phase drive linear ultrasonic motor.

A novel thin single-phase drive linear ultrasonic motor is proposed and tested in this paper. The proposed motor exhibits bidirectional driving via switching between the right-driving vibration mode (RD mode) and the left-driving vibration mode (LD mode). The structure and working principle of the motor are analyzed. Next, the finite element model of the motor is established and the dynamic performance is analyzed. A prototype motor is then fabricated, and its vibration characteristics are established via impedance testing. Finally, an experimental platform is built and the mechanical characteristics of the motor are experimentally investigated. The maximum no-load speed of the motor is ∼159.7 mm/s. With 8 N preload and 200 V voltage, the maximum thrust force of the motor in the RD and LD modes are ∼2.5 and 2.1 N, respectively. The motor possesses the advantages of being light in weight and thin structure and exhibiting an excellent performance. This work presents a new concept for the construction of ultrasonic actuators with bidirectional driving capacity.

Rapid extraction of valuable metals from spent LiNixCoyMn1-x-yO2 cathodes based on synergistic effects between organic acids.

The slow rate of organic acid leaching is the main factor hindering the ecological recycling of spent lithium-ion battery (LIB) cathode materials. Here, a mixed green reagent system of ascorbic acid and acetic acid is proposed to leach valuable metal ions from the spent LIBs cathode materials rapidly. In 10 min, 94.93% Li, 95.09% Ni, 97.62% Co, and 96.98% Mn were leached, according to the optimization results. Kinetic studies and material characterization technologies like XRD, SEM, XPS, UV-vis, and FTIR show that the "diffusion" and "stratification" effects of acetic acid contribute to the dual-function leaching agent ascorbic acid quickly extract metal ions from spent LiNi0.5Co0.3Mn0.2O2 (NCM532) materials at a mild temperature. In addition, the density-functional theory (DFT) calculations of spent NCM532 structural surfaces and leaching agents show that the fast leaching of valuable metal ions is due to the synergy between ascorbic acid and acetic acid. These results provided an approachable thinking for developing advanced and environmentally friendly strategies for recycling spent LIB cathode materials.

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

Advances in Hydrogel Adhesives for Gastrointestinal Wound Closure and Repair.

Millions of individuals undergo gastrointestinal (GI) tract surgeries each year with common postoperative complications including bleeding, perforation, anastomotic leakage, and infection. Today, techniques such as suturing and stapling seal internal wounds, and electrocoagulation stops bleeding. These methods induce secondary damage to the tissue and can be technically difficult to perform depending on the wound site location. To overcome these challenges and to further advance wound closure, hydrogel adhesives are being investigated to specifically target GI tract wounds because of their atraumatic nature, fluid-tight sealing capability, favorable wound healing properties, and facile application. However, challenges remain that limit their use, such as weak underwater adhesive strength, slow gelation, and/or acidic degradation. In this review, we summarize recent advances in hydrogel adhesives to treat various GI tract wounds, with a focus on novel material designs and compositions to combat the environment-specific challenges of GI injury. We conclude with a discussion of potential opportunities from both research and clinical perspectives.

Ag/Ag2O with NIR-Triggered Antibacterial Activities: Photocatalytic Sterilization Enhanced by Low-Temperature Photothermal Effect.

Purpose: A synergistic antibacterial system employing photocatalytic performance and low-temperature photothermal effect (LT-PTT) with the potential for infectious skin wound healing promotion was developed. Methods: Ag/Ag2O was synthesized with a two-step method, and its physicochemical properties were characterized. After its photocatalytic performance and photothermal effect were evaluated under 0.5 W/cm2 808 nm NIR laser irradiation, its antibacterial activities in both planktonic and biofilm forms were then studied in vitro targeting Staphylococcus Aureus (S. aureus), and the biocompatibility was tested with L-929 cell lines afterward. Finally, the animal model of dorsal skin wound infection was established on Sprague-Dawley rats and was used to assess infectious wound healing promotion of Ag/Ag2O in vivo. Results: Ag/Ag2O showed boosted photocatalytic performance and local temperature accumulation compared with Ag2O when exposed to 0.5 W/cm2 808 nm NIR irradiation, which therefore endowed Ag/Ag2O with the ability to kill pathogens rapidly and cleavage bacterial biofilm in vitro. Furthermore, after treatment with Ag/Ag2O and 0.5 W/cm2 808 nm NIR irradiation, infectious wounds of rats realized skin tissue regeneration from a histochemical level. Conclusion: By exhibiting excellent NIR-triggered photocatalytic sterilization ability enhanced by low-temperature photothermal effect, Ag/Ag2O was promising to be a novel, photo-responsive antibacterial agent.

Dental follicle cells-derived small extracellular vesicles inhibit pathogenicity of Porphyromonas gingivalis.

OBJECTIVE: It aims to explore the effect of dental follicle cells-derived small extracellular vesicles (D-sEVs) with or without lipopolysaccharides (LPS) pretreating on the pathogenicity of Porphyromonas gingivalis (P. gingivalis). METHODS: The antibacterial effects of D-sEV were evaluated by measuring the growth, biofilm formation, gingipains, and type IX secretion system (T9SS) expression of P. gingivalis. And the influence of D-sEV on P. gingivalis adhesion, invasion, cytotoxicity, and host immune response was examined in gingival epithelial cells (GECs). Then P. gingivalis treated with D-sEV was applied to investigate the pathogenicity in experimental periodontitis of mice. RESULTS: It showed that both D-sEV and P. gingivalis LPS-pretreated D-sEV (L-D-sEV) could target P. gingivalis, inhibit their growth and biofilm formation, and hinder the attachment and invasion in GECs, therefore remarkably decreasing P. gingivalis cytotoxicity and the expression of IL-1ß and IL-6 in GECs. In addition, they significantly reduced the expression of P. gingivalis virulence factors (gingipains and T9SS). In vivo, it showed that the bacteria in the gingiva were significantly decreased after sEV treatment. Meanwhile, less bone loss and fewer inflammatory cells infiltration and osteoclast formation in D-sEV and L-D-sEV groups. CONCLUSION: Both D-sEV and L-D-sEV were proven to inhibit the pathogenicity of P. gingivalis and thus prevented the development of periodontitis.

Near-Infrared-Enhanced Dual Enzyme-Mimicking Ag-TiO2-x@Alginate Microspheres with Antibactericidal and Oxygeneration Abilities to Treat Periodontitis.

The effective treatment for periodontitis is to completely and sustainedly eradicate the bacterial pathogens from the complex periodontal pockets. Local sustained-release antibiotics as a complementary treatment after scaling and root planning can sustainedly combat bacterial pathogens in the periodontal pockets to help treat the disease, but the increasing concern of bacterial resistance limits its future use. Here, we reported a local antibacterial system based on microsized multifunctional Ag-TiO2-x encapsulated in alginate (ATA) microspheres. We confirmed that ATA displayed strong photothermally enhanced dual enzyme-mimicking (peroxidase-like and catalase-like) activities and weak photocatalytic activity under 808 nm near-infrared (NIR) irradiation, which could boost the generation of reactive oxygen species (ROS) and O2 in the presence of low-level H2O2. As a result, the ATA/H2O2/NIR system exhibited efficient antibacterial activity against Porphyromonas gingivalis and Streptococcus gordonii in both planktonic and biofilm forms. With the help of ROS, ATA could release Ag+ in concentrations sufficient to inhibit periodontal pathogens as well. Moreover, the in situ-generated oxygen was supposed to alleviate the local hypoxic environment and would help downregulate the lipopolysaccharide-mediated inflammatory response of periodontal stem cells. The in vivo rat periodontitis treatment results demonstrated that the ATA/H2O2/NIR system reduced the bacterial load, relieved inflammation, and improved tissue healing. Our work developed a new local prolonged bactericidal and oxygenation system for enhanced periodontitis. Avoiding the usage of antibiotics and nanomaterials, this strategy showed great promise in adjunctive periodontitis treatment and also in other biomedical applications.

MiR-148a deletion protects from bone loss in physiological and estrogen-deficient mice by targeting NRP1.

Bone metabolic homeostasis is largely dependent on the dynamic balance between osteoblasts and osteoclasts. MicroRNAs (miRNAs) play critical roles in regulating bone metabolism. In this study, we explored the role of a new miRNA (miR-148a) in osteoporosis. We compared the bone phenotype between miR-148a knockout (KO) mice and the wild-type (WT) littermates. We found miR-148a KO mice exhibited an increased bone mass phenotype and decreased osteoclastogenesis compared to the WT group. In vitro, miR-148a overexpression promoted osteoclastogenesis and bone resorption function. Mechanistically, NRP1 was identified as a novel direct target of miR-148a, and NRP1 silencing reversed the effect of miR-148a knockout. In OVX and calvarial osteolysis models, miR-148a KO protects mice against excessive bone resorption, while miR-148a agomiR/AAV-shNRP1 accelerates pathologic bone loss. Finally, the miR-148a level was found to be positively correlated with ß-CTX in postmenopausal osteoporosis (PMOP) serum specimens. In summary, our findings revealed that miR-148a genetic deletion ameliorates bone loss under physiological and pathological conditions by targeting NRP1. In osteoclast-related bone metabolic diseases such as PMOP, miR-148a may be an attractive therapeutic target in the future.

Constructing mesoporous Zr-doped SiO2 onto efficient Z-scheme TiO2/g-C3N4 heterojunction for antibiotic degradation via adsorption-photocatalysis and mechanism insight.

Novel modified-TiO2/Zr-doped SiO2/g-C3N4 ternary composite is fabricated via an in-situ grow of porous Zr-SiO2 layer to TiO2/g-C3N4 heterojunction, which exhibits well adsorption-photocatalytic performance under simulated solar light irradiation. The nano-size mesoporous TiO2 are dispersed on the lamellar g-C3N4, and the Zr-SiO2 is in-situ fabricated onto the surface of g-C3N4 sheets. The adsorption occurs on the SiO2 layers, and doping Zr element to SiO2 enhances the adsorption of pollutants, while the photocatalytic reaction occurs on the valence band (VB) of TiO2 and conduction band (CB) of g-C3N4, which gives reactive oxygen species of ∙O2-, h+, and ∙OH for high efficient decomposition of antibiotics, i.e. berberine hydrochloride (98.11%), tetracycline (80.76%), and oxytetracycline (84.84%). The excellent adsorption capacity and Z-scheme photoinduced charge carrier migration behavior endowed the novel material with enhanced berberine hydrochloride (BH) removal in water, which approximately 2.5 and 3.8 folds than that of pure g-C3N4 and sole TiO2, respectively. Three degradation pathways are unraveled by LC-MS and theoretical calculations. Furthermore, the toxicity of intermediates was evaluated by the Toxicity Estimation Software Tool (T.E.S.T.), the result demonstrated a good application potential of M-TiO2/Zr-SiO2/g-C3N4 as an novel adsorptive photocatalyst.

Correction: Xie et al. Synergistic Effect of MoS2 and SiO2 Nanoparticles as Lubricant Additives for Magnesium Alloy-Steel Contacts. Nanomaterials 2017, 7, 154.

In the original publication [...].

Anatase quantum dots decorated silica/carbon lamellas for removal of antipsychotic drugs via adsorption-photocatalysis and toxicity evaluation.

In this work, discrete quantum dots of crystallized anatase TiO2 are successfully anchored on carbon nanosheets containing amorphous SiO2 via templated self-assembly and pyrolysis routes. The novel hybrid photocatalyst of TiO2/C/SiO2 exhibits well coupled adsorption and visible light photocatalysis on chlorpromazine (CPZ) and the rate constants are 0.0223 and 0.0198 min-1, respectively. The direct photocatalytic degradation of CPZ under static conditions reaches 91.1% within 3 h while a removal rate of 31.4% for CPZ could be retained under dynamic flow conditions, and the improved performance could be attributed to enhanced adsorption via SiO2/C and highly exposure of TiO2 QDs surface. Based on the trapping experiments, ESR, LC-MS, and toxicity evaluation, O2- free radicals are identified as main reactive species for CPZ degradation along three possible pathways, with reduced toxicities for its intermediates. The cell viability tests of photocatalytic-degraded solutions and the catalyst exhibit negligible toxicities for both intermediates and the material, suggesting the novel composite of TiO2/C/SiO2 as an environmental friendly photocatalyst for pharmaceutical wastewater treatment.

Gelatin methacryloyl-alginate core-shell microcapsules as efficient delivery platforms for prevascularized microtissues in endodontic regeneration.

Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was ∼359 µm, and that of GelMA cores was ∼278 µm. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDPSCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications. STATEMENT OF SIGNIFICANCE: Cell-laden microspheres combined with the proangiogenesis approach are promising in endodontic regeneration. We proposed GelMA-alginate core-shell microcapsules generated via the coaxial electrostatic microdroplet (CEM) method, which utilizes a double-lumen needle to allow for core-shell structures to form. The microcapsules were used for co-culturing hDPSCs and HUVECs to harvest large amounts of prevascularized microtissues, which further showed improved vascularization and pulp-like tissue regeneration in vivo. This CEM method and the microcapsule system have advantages of high-throughput generation, convenient collection, and avoid aggregation during long-term culturing. We proposed a high-effective platform for mass production of prevascularized microtissues, which exhibit great promise in the clinical transformation of endodontic regeneration and other applications in regenerative medicine.