Journal: Bioactive Materials

Article Title: Metformin alleviates aging-associated periodontitis via NRF2-mediated restoration of the IRE1α dependent unfolded protein response

doi: 10.1016/j.bioactmat.2026.03.060

Figure Lengend Snippet: Senescence-targeted, antibacterial, and hemostatic properties of composite hydrogels. (A) Fluorescence images of young and senescent PDLSCs (D-gal and LPS pretreated) incubated with Nile red (NR)-loaded Gal-MPDA for the indicated time periods. (B) Confocal fluorescence images showing the subcellular localization of GM@Nir in D-gal and LPS-induced senescent PDLSCs and cross-sectional analysis. Lysosome, Lyso tracker; Nuclei, Hoechst. (C) Live-dead staining for PDLSCs cells on day 1,3,5. (D) The viability of PDLSCs cells assessed by CCK-8 assay cocultured with composite hydrogels on day 1,3,5. (E) Representative optical images of the Hemolytic test after treating mouse blood with TA, TAM-GM, or TAM-GM@Met, followed by quantification analysis. (F) Live/dead staining of E. coli, S. aureus and P. gingivalis . ns, not significant. Data are presented as means ± SEM (n = 3 per subgroup). ∗∗∗P < 0.001.

Article Snippet: For fluorescence labeling, Nile red (HY-D0718, MCE) was added to 1 mg/mL MPDA nanoparticles and stirred at room temperature in the dark for 12 h. Then, galactan was added at a ratio of 1:2 with MPDA and stirred for another 12 h in the dark at room temperature.

Techniques: Fluorescence, Incubation, Staining, CCK-8 Assay

Journal: Bioactive Materials

Article Title: Metformin alleviates aging-associated periodontitis via NRF2-mediated restoration of the IRE1α dependent unfolded protein response

doi: 10.1016/j.bioactmat.2026.03.060

Figure Lengend Snippet: In vivo therapeutic effect of the TAM-GM@Met on mice with an aging-associated periodontitis model. (A) Schematic illustration of the therapeutic process on the D-gal induced aging mice periodontitis model. (B) Micro-CT reconstructions and buccal-palatal sectional views of maxillary molars and evaluation of the distance from the CEJ to the ABC. (C, D) Mice periodontal tissue sections prepared for H&E staining (C) and Masson's trichrome staining (D). (E) Schematic of TAM-GM@Met preparation. TAM hydrogel incorporates galactose-coated MPDA nanoparticles (GM) to target senescent cells for metformin delivery. Metformin activates NRF2, leading to transcriptional upregulation of IRE1α, restoration of the UPR, and suppression of SASP in PDLSCs. ns, not significant; TAM, tannic acid and Ag-MOFs based hydrogel; MPDA, mesoporous polydopamine; UPR, unfolded protein response. Data are presented as means ± SEM (n = 5 per subgroup). ∗∗∗P < 0.001.

Article Snippet: For fluorescence labeling, Nile red (HY-D0718, MCE) was added to 1 mg/mL MPDA nanoparticles and stirred at room temperature in the dark for 12 h. Then, galactan was added at a ratio of 1:2 with MPDA and stirred for another 12 h in the dark at room temperature.

Techniques: In Vivo, Micro-CT, Staining

Journal: Bioactive Materials

Article Title: Chiral Fe 3 O 4 /GelMA hydrogels regulate the osteoimmune microenvironment via Itgb3-mediated macrophage polarization to combat peri-implantitis

doi: 10.1016/j.bioactmat.2026.03.055

Figure Lengend Snippet: Synthesis and Characterization of Chiral Fe 3 O 4 /GelMA Hydrogels. (A) Synthesis procedure of chiral Fe 3 O 4 /GelMA hydrogels. (B) SEM image (scale bar: 30 μm, 30 nm) of bare Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. (C) UV-vis, (D) XRD spectra, and (E) CD spectra of bare Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. FT-IR spectra of (F1) L-cysteine and D-cysteine, and (F2) bare Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. (G1-3) Fe 2p XPS spectra of bare Fe₃O₄, D‑Fe₃O₄, and L‑Fe₃O₄ nanoparticles. (H) Zeta potential of Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. (I) Loading content of Fe 3 O 4 SPs in FG, D-FG and L-FG groups. (J1-2) General view and SEM cross-section view of the GelMA, Fe 3 O 4 /GelMA, D-Fe 3 O 4 /GelMA, L-Fe 3 O 4 /GelMA hydrogel (scale bar: 100 μm). (K1-2) Elemental spectrum analysis of chiral Fe 3 O 4 /GelMA hydrogel shows the presence of carbon (C), nitrogen (N), oxygen (O), sulfur (S), and iron (Fe). (L)The photocurable property of chiral hydrogels. (M) Degradation profile and (N) Swelling rate of the chiral Fe 3 O 4 /GelMA hydrogel. (O) Maximum compressive strength of chiral hydrogels. (P1-2) pH value and Zeta potential during degradation. (Q) Storage modulus (G′) and loss modulus (G″) versus frequency of chiral hydrogels. (n = 3, ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001). Abbreviation: SPs, superparticles; SEM, scanning electron microscopy; UV–vis, ultraviolet–visible; XRD, X-ray diffraction; CD, circular dichroism; FT-IR, Fourier-transform infrared spectroscopy.

Article Snippet: First, hydrophobic Fe 3 O 4 nanoparticles (NPs) (≥99.5%, 100 nm,C12834835, Macklin, Shanghai) were dispersed in n-hexane solvent, with amphiphilic sodium dodecyl sulfate (SDS, ≥99.0%, Sigma-Aldrich, #436143) as a surfactant and water, to form an oil-in-water emulsion under rapid stirring.

Techniques: Circular Dichroism, Zeta Potential Analyzer, Electron Microscopy, Fourier Transform Infrared Spectroscopy, Spectroscopy

Journal: Bioactive Materials

Article Title: Chiral Fe 3 O 4 /GelMA hydrogels regulate the osteoimmune microenvironment via Itgb3-mediated macrophage polarization to combat peri-implantitis

doi: 10.1016/j.bioactmat.2026.03.055

Figure Lengend Snippet: Evaluation of the biocompatibility, antimicrobial efficacy, and multi-enzyme mimetic activities of chiral Fe 3 O 4 /GelMA hydrogels. (A, B) Cell viability analysis using the CCK-8 assay showed the total activity of RAW264.7 cells and MC3T3-E1 interacting with Fe 3 O 4 /GelMA composite hydrogel without changing the medium. (C) Live/Dead staining of RAW264.7 and MC3T3-E1 cells after 72 h of culture. (green: live cells; red: dead cells) Scale bar: 100 μm. (D) After co-culturing with GelMA, FG, D-FG, and L-FG hydrogels for 72 h, fluorescence images of RAW264.7 and MC3T3-E1 cells were captured. F-actin stained with rhodamine-phalloidin (red), and cell nuclei were stained with DAPI (blue). Scale bar: 100 μm. (E) Crystal violet staining of Pg bacterial biofilms treated with GelMA, FG, D-FG and L-FG groups. (F) Illustration of the multi-enzyme mimetic activities of chiral Fe 3 O 4 . (G1) The UV–vis absorbance spectra of Fe 3 O 4 +TMB + H 2 O 2 . (G2) Lineweaver-Burk double reciprocal plots of Fe 3 O 4 corresponding to H 2 O 2 . (H1) WTS-8 assay to determine •O 2 − scavenging activities. (H2) Scavenging rate of •O 2 − with different concentration of Fe 3 O 4 . (I1) H 2 O 2 scavenging activities of D-, L-, and LD-Fe 3 O 4 . (I2) H 2 O 2 scavenging rate of D-, L-, and LD-Fe 3 O 4 at different concentrations (0–100 μg/mL). Abbreviation: CCK-8, Cell Counting Kit-8; Pg, Porphyromonas gingivalis ; TMB, 3,3′,5,5′-tetramethylbenzidine; H 2 O 2 , hydrogen peroxide; WST-8, water-soluble tetrazolium salt-8; ROS, reactive oxygen species.

Article Snippet: First, hydrophobic Fe 3 O 4 nanoparticles (NPs) (≥99.5%, 100 nm,C12834835, Macklin, Shanghai) were dispersed in n-hexane solvent, with amphiphilic sodium dodecyl sulfate (SDS, ≥99.0%, Sigma-Aldrich, #436143) as a surfactant and water, to form an oil-in-water emulsion under rapid stirring.

Techniques: CCK-8 Assay, Activity Assay, Staining, Fluorescence, Concentration Assay, Cell Counting

Journal: Bioactive Materials

Article Title: Chiral Fe 3 O 4 /GelMA hydrogels regulate the osteoimmune microenvironment via Itgb3-mediated macrophage polarization to combat peri-implantitis

doi: 10.1016/j.bioactmat.2026.03.055

Figure Lengend Snippet: Regulatory Effects of Chiral Hydrogels on the Bone Immune Microenvironment. (A, B) Immunofluorescence showed the expression of the M1 polarization marker CD86 (Green) and M2 polarization marker CD206 (Red) in GelMA, FG, L-FG and D-FG groups. Scale bar = 200 μm. (C, D) RT-qPCR results showing the expression of M1 polarization-associated factors Cd86 , Tnf , and Nos2 versus M2 polarization-associated factors Mrc1 , Arg1 , and Il10 in RAW264.7 cells after co-cultured with chiral Fe 3 O 4 /GelMA for 72 h. (E) Schematic of co-culture of RAW264.7 and MC3T3-E1 cells grown on hydrogel surfaces separated by a Transwell chamber. (F, G) Western Blot results showing the protein expression and quantification of CD206 and CD86 in RAW264.7 cells and (H, I) ALP and COL1 in MC3T3-E1 cells after co-cultured with chiral hydrogels. (J) Images of ALP staining on day 7 and 14 and (K) ARS staining on day 14 and 21. Scale bar = 200 μm. (n = 3, ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001). Abbreviation: RT-qPCR, reverse transcription quantitative polymerase chain reaction; WB, Western blot; ALP, alkaline phosphatase; ARS, Alizarin Red S.

Article Snippet: First, hydrophobic Fe 3 O 4 nanoparticles (NPs) (≥99.5%, 100 nm,C12834835, Macklin, Shanghai) were dispersed in n-hexane solvent, with amphiphilic sodium dodecyl sulfate (SDS, ≥99.0%, Sigma-Aldrich, #436143) as a surfactant and water, to form an oil-in-water emulsion under rapid stirring.

Techniques: Immunofluorescence, Expressing, Marker, Quantitative RT-PCR, Cell Culture, Co-Culture Assay, Western Blot, Staining, Reverse Transcription, Real-time Polymerase Chain Reaction

Journal: Bioactive Materials

Article Title: A safe and anti-inflammatory plant-derived nanovesicle platform for targeted delivery in acute lung injury

doi: 10.1016/j.bioactmat.2026.03.033

Figure Lengend Snippet: Synthesis and characterization of GRb1@LEVS-cRGD. (a) Transmission electron microscopy (TEM) images of lemon‐derived EVs (LEVs), GRb1, GRb1@LEVs, and GRb1@LEVs-cRGD. (b) Fluorescence emission spectra of GRb1@LEVs. LEVs was doped with DiD and DiI, and then mixed with increasing amount of GRb1. (c) CLSM image of GRb1@LEVs prepared from DiO-labeled GRb1 (green) and DiD-labeled LEVs (red). (d) CLSM image of GRb1@LEVs-cRGD prepared from Chol-PEG 2000 -cRGD-FITC (green) and DiD-LEVs (red). (e) Hydrodynamic size distribution of nanoparticles determined by DLS. f) Zeta potentials of LEVs, GRb1, GRb1@LEVs, and GRb1@LEVs-cRGD (n = 3). (g-h) The stability on size (g) and zeta potential (h) of GRb1@LEVs-cRGD in PBS or PBS containing 10% FBS medium for 5 weeks (n = 3). (i) Schematic illustration of antibiotics remote loading into vesicles. (j) TIG loading yield at different cholesterol inputs (n = 3). (k) Loading yield at different TIG input (n = 3).

Article Snippet: Dynamic light scattering (DLS) and zeta potential were obtained by using a nanoparticle size and zeta potentiometer (Omni, Brookhaven Co., USA).

Techniques: Transmission Assay, Electron Microscopy, Derivative Assay, Fluorescence, Labeling, Zeta Potential Analyzer

Journal: Bioactive Materials

Article Title: A safe and anti-inflammatory plant-derived nanovesicle platform for targeted delivery in acute lung injury

doi: 10.1016/j.bioactmat.2026.03.033

Figure Lengend Snippet: In vitro and in vivo targeted delivery of GRb1@LEVs-cRGD (a-b) confocal microscopy images of the uptake of nanoparticles by RAW 264.7 (a) and HUVEC cells (b) under inflammation and physiological conditions. (c-d) The corresponding quantitative analysis in RAW 264.7 (c) and HUVEC cells (d), respectively (n = 5). (e-f) IVIS images showing the fluorescent distribution in the heart, liver, spleen, lung, and kidney at 2 h after injection of Cy5.5-labeled vesicles (e), along with the corresponding quantification of mean fluorescent intensity (f) (n = 3). (g) Corresponding fluorescence intensity quantification of lung at different times (n = 3). (h) Uptake distribution of GRb1@LEVs-cRGD in various lung cell types (n = 3).

Article Snippet: Dynamic light scattering (DLS) and zeta potential were obtained by using a nanoparticle size and zeta potentiometer (Omni, Brookhaven Co., USA).

Techniques: In Vitro, In Vivo, Confocal Microscopy, Injection, Labeling, Fluorescence

Journal: Bioactive Materials

Article Title: A safe and anti-inflammatory plant-derived nanovesicle platform for targeted delivery in acute lung injury

doi: 10.1016/j.bioactmat.2026.03.033

Figure Lengend Snippet: The anti-inflammatory effect of the nanoparticles in vitro (a) The proportion of CD86 M1 and CD206 M2 in RAW264.7 cells by flow cytometry. (b-c) Level of inflammatory cytokines IL-6, TNF-α and IL-10 in LPS-stimulated RAW 264.7 cells (b) and MH-S cells (c) after different treatments (n = 5). (d-e) NF-κB p65 nuclear translocation observed by CLSM (n = 5). ①control group; ② PBS treated group; ③ LEVs treated group; ④ GRb1 treated group; ⑤ GRb1@LEVs treated group; ⑥ GRb1@LEVs-cRGD treated group. (f) The protein expressions of key members in the NF-κB pathway by Western blot, including the phosphorylated (p-p65) and basal NF-κB p65, p-IκBα, and IκBα (n = 3). (g) Heat map showing the hierarchical clustering results of the DEGs detected between LPS group and LPS treated with GRb1@LEVs-cRGD group. DEGs were identified based on a fold change greater than 1.5 and an adjusted P-value less than 0.05. (g) Gene Ontology (GO) term enrichment analysis was performed, and the top 30 significantly enriched GO terms were selected based on an FDR <0.05. (h) Top 20 enriched pathways identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs in cells triggered with LPS. (i-j) Gene Set Enrichment Analysis (GSEA) images. (l) Schematic illustration of the mechanism in the reprogramming of RAW 264.7 cells by GRb1@LEVs-cRGD.

Article Snippet: Dynamic light scattering (DLS) and zeta potential were obtained by using a nanoparticle size and zeta potentiometer (Omni, Brookhaven Co., USA).

Techniques: In Vitro, Flow Cytometry, Translocation Assay, Western Blot

Journal: Bioactive Materials

Article Title: Chiral Fe 3 O 4 /GelMA hydrogels regulate the osteoimmune microenvironment via Itgb3-mediated macrophage polarization to combat peri-implantitis

doi: 10.1016/j.bioactmat.2026.03.055

Figure Lengend Snippet: Synthesis and Characterization of Chiral Fe 3 O 4 /GelMA Hydrogels. (A) Synthesis procedure of chiral Fe 3 O 4 /GelMA hydrogels. (B) SEM image (scale bar: 30 μm, 30 nm) of bare Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. (C) UV-vis, (D) XRD spectra, and (E) CD spectra of bare Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. FT-IR spectra of (F1) L-cysteine and D-cysteine, and (F2) bare Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. (G1-3) Fe 2p XPS spectra of bare Fe₃O₄, D‑Fe₃O₄, and L‑Fe₃O₄ nanoparticles. (H) Zeta potential of Fe 3 O 4 SPs, D-Fe 3 O 4 SPs and L-Fe 3 O 4 SPs. (I) Loading content of Fe 3 O 4 SPs in FG, D-FG and L-FG groups. (J1-2) General view and SEM cross-section view of the GelMA, Fe 3 O 4 /GelMA, D-Fe 3 O 4 /GelMA, L-Fe 3 O 4 /GelMA hydrogel (scale bar: 100 μm). (K1-2) Elemental spectrum analysis of chiral Fe 3 O 4 /GelMA hydrogel shows the presence of carbon (C), nitrogen (N), oxygen (O), sulfur (S), and iron (Fe). (L)The photocurable property of chiral hydrogels. (M) Degradation profile and (N) Swelling rate of the chiral Fe 3 O 4 /GelMA hydrogel. (O) Maximum compressive strength of chiral hydrogels. (P1-2) pH value and Zeta potential during degradation. (Q) Storage modulus (G′) and loss modulus (G″) versus frequency of chiral hydrogels. (n = 3, ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001). Abbreviation: SPs, superparticles; SEM, scanning electron microscopy; UV–vis, ultraviolet–visible; XRD, X-ray diffraction; CD, circular dichroism; FT-IR, Fourier-transform infrared spectroscopy.

Article Snippet: Surface potentials of the three nanoparticle types were determined using a nanoparticle size and zeta potential analyzer (ZS90, Malvern Zetasizer Nano, UK).

Techniques: Circular Dichroism, Zeta Potential Analyzer, Electron Microscopy, Fourier Transform Infrared Spectroscopy, Spectroscopy