The conventional therapeutic approaches for oral diseases primarily encompass dental restoration, pulp therapy, and maxillofacial surgical interventions. However, these methods are difficult to promote tissue regeneration and immune regulation. Mesenchymal stem cell-derived exosomes (MSC-Exos), mainly derived from tissues such as bone marrow, umbilical cord blood, umbilical cord, placenta, and fat, have been used to study the treatment of oral diseases. Conventional MSCs-Exos have relatively low immunogenicity and ethical issues, but exosomes derived from dental mesenchymal stem cells (DSCs) not only have abundant sources but also lower immunogenicity, which can circumvent ethical restrictions. This review aims to comprehensively investigate the isolation and characterization methods of exosomes derived from dental-derived mesenchymal stem cells (DSC-Exos) as well as their sources and biological properties. It further reviews recent advances in their application within the field of stomatology and summarizes various material-based delivery systems for exosomes. Particular emphasis is placed on their therapeutic potential in inflammatory conditions such as pulpitis, periodontitis, temporomandibular joint disorders, and immune-related diseases, as well as the application prospects of inducing cell directional differentiation in pulp-dentin complex regeneration, jawbone repair, and soft tissue regeneration. In addition, we have reviewed here some possible applications of DSC-Exos to prevent orthodontic relapse and treat oral cancer. The DSC-Exos play multiple roles, including anti-inflammatory activity, immunomodulatory effect, and tissue regeneration, and have a great potential in the clinical treatment of oral inflammation, tissue defects, and immune dysregulation. Their therapeutic efficacy could also be improved by combining them with other biomaterials.

Periodontitis is driven by a self-reinforcing cycle of persistent inflammation and cellular senescence, further exacerbated by pathogenic microbial colonization. To address this challenge, inspired by the "fortress effect", we report an allicin-based nanoplatform of biolubrication (PPCG) that establishes a physical and biological protective barrier for precise modulation of the periodontal microenvironment. PPCG integrates hydration-lubricating diblock copolymer P(DMA-bMPC) (PDMPC) with bioactive allicin. The lubricating PDMPC barrier may suppress pathogenic microbial adhesion and biofilm formation, constituting an "outer fortress wall" against bacterial invasion. Concurrently, sustained release of allicin could regulate bone marrow mesenchymal stem cells (BMMSCs) and mitigate inflammatory responses. It could preserve stemness and multipotent differentiation potential, thereby forming an "inner defensive citadel" that promotes soft and hard tissue regeneration. This dual protective barrier can markedly attenuate periodontal tissue senescence and inflammatory and prevent alveolar bone loss in mice periodontitis model. Furthermore, PPCG could rebalance the oral microbiota and maintain ecological homeostasis. Therapeutic efficacy is also corroborated using an artificial intelligence-assisted detection system based on the YOLO v8 deep learning model. Collectively, this study presents a therapeutic intervention strategy for periodontitis, offering a scalable and translational approach for treating inflammation and senescence.

Periodontitis, driven by oral-gut microbiota dysbiosis and NLRP3 inflammasome activation, lacks effective natural therapeutic strategies. This study investigated naringin (Nar), a grapefruit peel flavonoid, using ligature-induced periodontitis in rats and LPS-stimulated RAW264.7 cells. Nar treatment significantly reduced alveolar bone loss, inhibited NLRP3 inflammasome activation (NLRP3, IL-1β), and suppressed inflammatory mediators (COX2, iNOS, IL-6, TNF-α) while improving collagen organisation. Microbiome analysis revealed that Nar suppressed pathogenic bacteria (Veillonella orally, Escherichia-Shigella in the gut) and enriched beneficial Lactobacillus. Metabolomics analysis revealed a significant decrease in the abundance of arginyl-glutamine (arg-gln) in the intestines of rats with periodontitis. Both Nar and arg-gln activated the AMPK/Nrf2 pathway, suppressing NLRP3 activation. FMT from Nar-treated donors had similar anti-inflammatory effects. In conclusion, Nar alleviates periodontitis primarily by directly activating the AMPK/Nrf2 pathway and inhibiting NLRP3 inflammasome activation in periodontal tissues. Additionally, Nar reshapes the gut microbiota to elevate arg-gln levels, which further amplifies AMPK activation and contributes to inflammation control, but is not sufficient alone to drive structural repair. These findings provide a novel theoretical basis for natural compound-mediated microbiota and inflammatory regulation in periodontitis treatment.

The characteristic oral environment – with its dynamic clearance, moisture, microbial load, and inflammatory potential – makes oral diseases highly prevalent and therapeutically challenging. Metal-organic frameworks (MOFs), an emerging class of inorganic–organic hybrid porous coordination materials, have become pivotal in modern biomedical engineering due to their facile synthesis, high surface area, large loading capacity, exceptional ion storage capability, tunable composition and pore size, and pH-responsive behaviour. To further enhance their performance, bimetallic metal-organic frameworks (BMOFs) have been constructed by incorporating two metal ions with functionalized organic ligands. Leveraging synergistic multimetallic effects and structural tunability, BMOFs exhibit significant potential in biomedical applications, including antibacterial activity, catalysis, and drug delivery. Exploratory applications of BMOFs in the prevention and treatment of oral diseases have already emerged, spanning periodontitis management, caries prevention, oral tissue regeneration, and targeted cancer therapy. Nevertheless, challenges remain in terms of biosafety, long-term stability, in vivo degradation behaviour, and scalable fabrication. This review summarizes the synthesis strategies and functionalization approaches of BMOFs, the selection of metal pairs, and their synergistic mechanisms, with a focus on their applications in oral biofilm infections, inflammatory diseases, oromaxillofacial bone tissue engineering scaffolds, and cancer therapy. Additionally, it discusses current challenges related to biocompatibility, technical limitations, and the clinical translation of these technologies. By correlating the fundamental design principles of BMOFs with the diagnostic and therapeutic demands of oral diseases, this review aims to facilitate translational research and promote the development of BMOFs as innovative and efficient strategies for addressing a range of oral pathologies.

Mechanical tensile forces play a crucial role in modulating bone tissue behavior and the response of surrounding cells in vivo. During orthodontic tooth movement, tensile stresses within the periodontal ligament on the tension side stimulate bone deposition. Drawing inspiration from this biological process, our work introduces a strategy using mechanically active materials to enhance bone defect healing. We utilize liquid crystal elastomers (LCEs), a class of soft active materials known for excellent actuation performance. LCEs apply stable mechanical forces to target bone tissue, mimicking the traction of the periodontal ligament and actively promoting bone regeneration. By employing a sequential thiol-Michael/thiol-ene click reaction, optimizing component ratios, and utilizing low-temperature crosslinking, the driving temperature of LCE was significantly reduced to 27.3 °C. This advancement eliminates limitations on its medical applications in tissue regeneration. Moreover, both in vitro and in vivo experiments confirm that LCE-induced tensile forces enhance bone regeneration. The LAMB1-ITGB4 signaling axis mediates the process via the PI3K-AKT pathway. This mechanobiological approach opens new avenues for bone defect healing and provides mechanistic insights into how mechanical tensile forces promote bone regeneration.

Sericin is a waste material from the silk production process, researchers its found to have good biological activity and is widely used in tissue engineering. The aim of this paper is to summarize the biological applications of sericin in the field of bone tissue engineering and their research progress. Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic evaluations. MEDLINE, PubMed, and Google Scholar were searched using keywords. Sericin, has the ability to promote cell proliferation and angiogenesis. It also has excellent bone regenerative properties such as promoting osteoblast differentiation. Sericin itself has excellent physicochemical properties and can be processed into materials with different properties for bone regeneration engineering. Bone defects due to various skeletal diseases or surgical needs, etc are a major challenge for clinical treatment. Modern tissue engineering using synthetic osteogenic active materials offers another therapeutic option for bone defects, and sericin is expected to play a greater role as a promising biological material.

Periodontitis is a chronic inflammatory disease; its persistent inflammatory cascade leads to destruction of periodontal tissues and alveolar bone resorption. Isorhapontigenin (ISO) is an orally available dietary polyphenol. As a resveratrol analog, it exhibits stronger anti-inflammatory activity, yet its functional role and molecular mechanisms in periodontitis remain unclear. This study investigated the anti-inflammatory effects of ISO on periodontitis and its potential molecular mechanisms using a rat periodontitis model and lipopolysaccharide (LPS)-induced human gingival fibroblasts (HGFs) cell model. ISO effectively reduced inflammatory infiltration in gingival tissue while promoting alveolar bone repair and tissue remodeling. Integrated network pharmacology and bioinformatics analysis suggested the EGFR/PI3K/AKT signaling pathway as a potential key target. Mechanistic studies demonstrated that ISO inhibits LPS-mediated phosphorylation of EGFR and its downstream PI3K/AKT in HGFs, thereby blocking inflammatory signaling. In vivo, ISO significantly downregulated the expression of proteins in the EGFR/PI3K/AKT pathway and related inflammatory factors. In summary, this work confirmed for the first time that ISO significantly reduces inflammatory responses and tissue destruction in periodontitis, at least in part, by regulating the EGFR/PI3K/AKT pathway, providing both experimental and theoretical support for its development as an adjunctive anti-inflammatory drug for periodontal disease.

Background Hypertrophic scarring is an abnormal condition involving excessive fibroblast activation, aberrant extracellular matrix deposition, and persistent inflammation. Current treatments have limited efficacy and potential adverse effects, necessitating the development of new approaches. Purpose In this study, we investigated the effects of artesunate (ART) on hypertrophic scar (HS) formation and explored the underlying cellular and molecular mechanisms. Methods ART was local injected in rabbit ear HS model to study its effect on HS formation. Cell viability was assessed using the CCK8 assay. Cell proliferation and targeted protein expression were detected by flow cytometry, immunofluorescence and immunohistochemistry staining. Scratch assays were performed to evaluate cell migration, while western blotting analysis was used to detect changes in protein expression. Results Local injection of ART significantly reduced scar protrusion and thickness, improved the immune microenvironment, and attenuated collagen deposition. ART suppressed fibroblast activation, endothelial-mesenchymal transition (EndMT), and angiogenesis in HS tissues. In vitro, ART inhibited TGF-beta 1triggered fibroblasts activation and EndMT of human umbilical vein endothelial cells. Mechanistically, ART attenuated the activation of PI3K/AKT/mTOR and TGF-beta/Smad pathways in both fibroblasts and human umbilical vein endothelial cells. Notably, the mTOR activator 740 Y-P reversed the fibrosis-inhibiting effects of ART in vitro and in vivo, highlighting the critical and intriguing role of PI3K/AKT/mTOR signaling in mediating the effects of ART. Furthermore, we first uncovered a crosstalk between PI3K/AKT/mTOR and TGF-beta/Smad pathways, wherein PI3K/AKT/mTOR inactivation by ART partially contributed to the inhibition of TGF-beta/Smad signaling. Conclusion In addition to fibroblast activation, our findings first demonstrate that ART effectively mitigates HS formation by modulating the immune microenvironment and inhibiting EndMT and fibroblast activation. These results provide new perspectives into the development of HS and underscore the promising potential of ART as a therapeutic option for debilitating condition.

Combined radiation and wound injury (CRWI), caused by the interaction between radiation and trauma, presents major challenges to wound healing and is a key focus in trauma and radiation medicine. This study developed a microsphere-encapsulated composite hydrogel loaded with leptin (LP) and vascular endothelial growth factor (VEGF) to enhance CRWI wound healing. Drug-loaded sodium alginate (SA) microspheres were fabricated using the emulsion cross-linking method and integrated into thermosensitive Pluronic hydrogel to form the VEGF/LP-SA@P nanodelivery system. The microspheres’ physicochemical properties were characterized using scanning electron microscopy (SEM), rheometry, and enzyme-linked immunosorbent assay (ELISA) kits. The results showed that the microspheres had an intact structure with uniform size distribution, LP and VEGF encapsulation efficiencies of 48.01

Hypoxia and lactate metabolism are both distinctive characteristics of cancerous cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent forms of cancer. The objective of this study was to construct a prognostic model of genes related to hypoxia and lactate metabolism in order to facilitate the study of the prognosis, tumor immune microenvironment and therapeutic response of patients with HNSCC. The RNA-seq and clinical data for HNSCC were obtained from The Cancer Genome Atlas database and gene expression omnibus. The hypoxia- and lactate metabolism-related genes were obtained from the Molecular Signatures Database. The identification of differentially expressed genes was conducted using the "limma" R package. Subsequently, protein-protein interaction networks of the differentially expressed genes were constructed using the STRING database and Cytoscape software. A hypoxia-lactate metabolism-related prognostic model was constructed through the application of univariate Cox regression, random survival forest, and stepwise multivariate Cox regression analyses. Subsequently, further analyses were conducted, including principal component analysis, gene enrichment analysis, CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts), ImmuCellAI, ESTIMATE, tumor immune dysfunction and exclusion, IPS, oncoPredict, and CellMiner. These were performed to analyze the differences in immune landscapes and treatment responses. The results of our study demonstrate that hypoxia- and lactate metabolism-related features are promising biomarkers for predicting outcomes in patients with HNSCC.

OBJECTIVE:This review systematically summarizes recent advances in plasma applications for dentin bonding, antibacterial enhancement, and implant surface modification. DATA:A systematic literature search was conducted across four electronic databases: Medline via PubMed, Cochrane Library, Wiley Online Library, and Web of Science. The search was performed from inception until August 2025. SOURCES:154 publications were included in this review. STUDY SELECTION:The keywords used included combinations of MeSH and free-text terms such as 'cold atmospheric pressure plasma', 'CAP', 'dentin bonding', 'antibacterial', and 'implant surface modification'. Two reviewers independently screened titles and abstracts, followed by full-text evaluation. Disagreements were resolved by a third reviewer. Inclusion criteria were: (1) original research articles, (2) studies involving CAP in prosthodontics, (3) published in English. Exclusion criteria included: case reports, editorials, and conference abstracts. CONCLUSION:CAP can enhance the penetration and polymerization of resin monomers in dentin bonding, improve bond strength, and reduce microleakage due to its highly active substances. Additionally, CAP has exhibited notable antibacterial properties, as its reactive oxygen and nitrogen effectively inactivate oral bacteria and biofilm, thereby reducing the likelihood of drug resistance. Furthermore, CAP treatment may enhance implant surface properties, promote osseointegration, lower infection risk, and promote soft-tissue healing. CLINICAL SIGNIFICANCE:CAP is anticipated to address the challenges encountered in prosthodontics, including dentin bonding, antimicrobial properties, and implant surface modification. Consequently, CAP is expected to provide an innovative solution for the functionalization and longevity of dental restorations with the prospect of future chairside application.

Mandibular bone defects are a common clinical challenge for oral surgeons, and extensive research has been dedicated to developing bone scaffold substitutes. 3D printing is a common strategy for constructing personalized scaffolds to treat mandibular defects. Carboxylated multiwalled carbon nanotubes (MWCNTs) and bacterial cellulose (BC) were used to construct composites with 0, 0.25, 0.5, and 1 wt% gradients. Based on physicochemical properties, bioactivity, and osteogenic performance, 1 wt% MWCNT@BC was selected as the optimal filler for polycaprolactone (PCL). A novel top-heating 3D printing method was employed to construct a bone tissue engineering scaffold that exhibited a suitable scaffold morphology and enhanced mechanical properties, with a compressive strength reaching 85.99 ± 10.03 MPa. Cellular experiments demonstrated that the scaffold possessed good biocompatibility, cell adhesion properties, and effective osteoinductive performance. This was corroborated by a rat mandibular defect model that showed excellent biocompatibility and mandibular repair capabilities in vivo. In conclusion, this study addressed the previously unexplored impact of determined dispersion levels of MWCNTs on BC when used as a filler in PCL to ultimately offer new insights into their functional and regenerative potential. Furthermore, we established a novel three-dimensional (3D) printed bone tissue engineering scaffold, offering a new approach for the clinical treatment of mandibular bone defects.

Ferroptosis, caused by abnormal iron metabolism and lipid peroxidation, has been linked to pathogenic processes in several disorders. Its function and regulating mechanisms in periodontitis are still unclear, nevertheless. As a naturally derived phenolic diterpenoid molecule, carnosic acid (CA) serves multiple biological roles, including antioxidant, anti-inflammatory, and cytoprotective properties. Its potential for intervention in periodontitis and ferroptosis warrants further exploration. In this investigation, we combined network pharmacology analysis with in vitro and in vivo experimental validation to systematically evaluate the mechanism of action of CA intervention in periodontitis. Through an intersectional analysis of drug targets, ferroptosis-related genes, and periodontitis-related genes, potential core targets were identified, and GO/KEGG enrichment analysis was performed. The results suggest that Nrf2 is at the core of the protein interaction network and is significantly enriched in antioxidant response and iron homeostasis regulation pathways. Subsequently, changes in ROS, MDA, GSH, SOD, Fe²⁺, and other indicators, as well as the expression of ferroptosis-related indicators (GPX4, SLC7A11, FTH1), were detected in LPS-induced RAW264.7 cell models and rat periodontal ligation models. The key role of Nrf2 was verified using the Nrf2-specific inhibitor ML385. Network pharmacology results indicate that ferroptosis is crucial in the potential mechanism of CA action on periodontitis. Nrf2 is the core regulatory molecule connecting CA, periodontitis, and ferroptosis. The experimental results revealed that CA dramatically lowered ROS and MDA levels in cells and periodontal tissues, inhibited the accumulation of Fe²⁺, elevated the contents of GSH and SOD, and GPX4, SLC7A11, and FTH1 expression. Mechanistic studies have found that CA restores the antioxidant and iron homeostasis regulatory system by activating the Nrf2/GPX4 signaling axis, thereby inhibiting the vicious cycle of ferroptosis. After Nrf2 was blocked by ML385, the anti-ferroptosis and anti-inflammatory effects of CA were significantly weakened. The current research is the first to elucidate that CA can alleviate periodontitis pathological damage by suppressing ferroptosis via activating the Nrf2/GPX4 signaling axis. This enriches the pharmacological action spectrum of CA and provides new targets and a theoretical basis for periodontitis intervention strategies based on ferroptosis regulation.

Macrophages undertake pivotal yet dichotomous functions during skin wound healing, mediating both early proinflammatory immune activation and late anti-inflammatory tissue remodeling processes. The timely phenotypic transition of macrophages from inflammatory M1 to proresolving M2 activation states is essential for efficient healing. However, the endogenous mechanisms calibrating macrophage polarization in accordance with the evolving tissue milieu remain undefined. In this study, we reveal an indispensable immunomodulatory role for fibroblast-secreted exosomes in directing macrophage activation dynamics. Fibroblast-derived exosomes permitted spatiotemporal coordination of macrophage phenotypes independent of direct intercellular contact. Exosomes enhanced macrophage sensitivity to both M1 and M2 polarizing stimuli, yet they also accelerated timely switching from M1 to M2 phenotypes. Exosome inhibition dysregulated macrophage responses, resulting in aberrant inflammation and impaired healing, whereas provision of exogenous fibroblast-derived exosomes corrected defects. Topical application of fibroblast-derived exosomes onto chronic diabetic wounds normalized dysregulated macrophage activation to resolve inflammation and restore productive healing. Our findings elucidate fibroblast-secreted exosomes as remote programmers of macrophage polarization that calibrate immunological transitions essential for tissue repair. Harnessing exosomes represents a previously unreported approach to steer productive macrophage activation states with immense therapeutic potential for promoting healing in chronic inflammatory disorders.

Periodontitis, recognized as a chronic inflammatory condition, manifests through sustained gingival inflammation and gradual degradation of alveolar bone tissue. Without proper intervention, this pathological process may culminate in permanent tooth detachment. Consequently, therapeutic strategies for periodontitis primarily focus on mitigating inflammatory reactions and stimulating osseous tissue regeneration. Recent pharmacological investigations have highlighted artesunate (ART) as a compound exhibiting notable anti-inflammatory efficacy, though its clinical application is constrained by limited aqueous solubility and suboptimal pharmacokinetic properties. Carbon-based quantum dots, emerging as versatile nanoscale materials, demonstrate multiple biological functionalities. This research successfully synthesized artesunate-derived carbon dots (ACDs) through hydrothermal synthesis and comprehensively evaluated their dual therapeutic effects on inflammation suppression and bone formation enhancement in periodontal disease models. Experimental data revealed that ACDs exhibit improved hydrophilicity, favorable biocompatibility, and simultaneous anti-inflammatory/osteogenic capabilities. Mechanistically, ACDs activated the adenosine monophosphate-activated protein kinase (AMPK), subsequently inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling transduction, which effectively reduced pro-inflammatory cytokine secretion. AMPK pathway activation further upregulated expression patterns of osteogenic differentiation markers at both mRNA translation and protein synthesis levels, enhanced mineralization capacity in rat bone marrow mesenchymal stem cells (rBMSCs), and increased calcified nodule formation. Collectively, these findings demonstrate that ACDs effectively counteract lipopolysaccharide (LPS)-induced inflammatory responses while substantially improving bone regenerative processes through AMPK pathway modulation. This investigation suggests ACDs as a promising nanotechnology-based approach for periodontitis management.

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-alpha+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts. STING regulates the macrophage trafficking through STAT3 in wound healing.

For diabetic patients, impaired wound healing is a serious complication, which characterized by prolonged inflammation, wound granulation tissue formation obstruction and impaired re-epithelialization. Accumulating evidence shows that senescent cells play a crucial role in the pathomechanism of diabetic wounds. In this study, we systematically evaluated the role of senescent cells in diabetic wound healing through diabetic mice (DM mice) model (including streptozotocin-induced type I DM mice model and db/db (type II DM) mice model, and actively assessed the therapeutic potential of ProcyanidinC1 (PCC1), the novel senolytic compound. We demonstrated that diabetic mice accumulated a significant number of senescent cells, primarily fibroblasts, in their normal skin and wound tissues. Local application of PCC1 selectively eliminated these senescent cells, leading to improved wound healing outcomes. By modulating the NF-κB signaling axis, PCC1 administration effectively downregulated senescence-associated secretory phenotype components, thereby ameliorating immune dysregulation in diabetic wounds. This therapeutic intervention concurrently revitalized the functional capacity of dermal fibroblasts and vascular endothelial cells, while stimulating coordinated matrix deposition and architectural remodeling of the extracellular compartment. Furthermore, PCC1 treatment enhanced epidermal barrier function after healing, a crucial aspect of wound repair which is often impaired in diabetes. And we also found that PCC1 would improve wound healing at type II diabetic mouse. Collectively, our findings elucidate the complex detrimental roles of senescent cells in diabetic wound repair and establish PCC1-mediated senolytic clearance as a promising therapeutic intervention.

Efferocytosis of macrophages infiltrated in psoriatic lesions is mostly impaired, thus promoting the progression of psoriasis. Herein, we reveal that there exists a feedback loop between activated platelets and efferocytosis-impaired macrophages in psoriatic. Or rather, efferocytosis-impaired macrophages stimulate platelet activation, which in turn down-regulates the expression of the phagocytic receptor Mer on macrophages and polarizes macrophages to the M1-phenotype of weaker efferocytosis ability. Therefore, we construct a combined nanoplatform for more precise targeting to efferocytosis-impaired macrophages and activated platelets. The macrophage-targeting part of the nanoplatform efficiently orientates to efferocytosis-impaired macrophages through macrophage membrane encapsulation and targeting peptide modification. This increases the expression of Mer, simultaneously enhances the acidification and maturation of efferosomes, ultimately restores efferocytosis of macrophages, and promotes the phagocytosis and clearance of apoptotic cells. On the other hand, the activated platelet-targeting nanoparticles inhibit the activation of platelets, thus blocking the feedback loop and eventually preventing the down-regulation of Mer expression on macrophages. Furthermore, the combined nanoplatform suppresses the infiltration of macrophages and platelets in psoriatic lesions, reduces the release of pro-inflammatory factors such as IL-17A, and consequently improves the therapeutic effect of psoriasis and prevention of its recurrence in vivo. Collectively, this two-pronged strategy with multifunctionality in repairing efferocytosis, inhibiting platelet activation, and blocking the feedback loop may provide options available for the treatment of psoriasis.

Driven by abnormal activation of Toll-like receptor 7 (TLR7), systemic lupus erythematosus (SLE) exhibits severe efferocytosis impairment of macrophages, leading to the accumulation of antigenic substances and an imbalance of cellular homeostasis in other immune cells, with the most pronounced effect on platelets. While the macrophage-platelet feedback loop exists, solely restoring impaired efferocytosis of macrophages is insufficient to fully recover platelet levels in SLE. To rescue the disrupted immunity, two cell membrane-biomimetic nano-systems are designed: i) an engineered macrophage membrane-coated nanosponge carrying TLR7 inhibitors that specifically target inflammatory sites; ii) a resting platelet membrane-coated biomimetic nano-platform loaded with platelet activation inhibitors. The drug-loading nanosponge selectively adsorbs pro-inflammatory cytokines while targeting and repairing impaired efferocytosis. In parallel, the platelet membrane-coated nano-platform precisely targets activated platelets, effectively inhibiting their activation. The combined engineered nanosponge platform application mitigates inflammatory cell infiltration, upregulates Treg cells levels, which inhibits immune system hyperactivation, and restores key SLE-related indicators, alleviating SLE complications such as lupus nephritis and thrombocytopenia in different disease courses of SLE. Overall, the study not only discloses the association between TLR7 and efferocytosis, but also pioneers the treatment of SLE via inhibiting macrophage TLR7 and platelet-activating, offering novel therapeutic insights for SLE management.