Achieving scarless healing combined with skin appendage regeneration remains an extremely challenging task in the treatment of skin wounds. Vitamin A derivatives have shown great potential for follicle neogenesis and scarless repair but suffer from poor solubility, instability, photosensitivity, and toxicity in wound healing processes. Here, we present a multifunctional bioadhesive hydrogel system that integrates polydopamine (PDA) nanoparticles with vitamin A derivatives to promote functional skin regeneration. The PDA nanoparticles stabilized and enabled pH-responsive release of vitamin A derivatives, while simultaneously providing reactive oxygen species (ROS) scavenging and antioxidant protection. Embedded within an imine-crosslinked adhesive hydrogel network, this platform achieved strong tissue adhesion, sustained drug delivery, and favorable immune microenvironment modulation. In vivo, using both rat burn wounds and rabbit hypertrophic scar models, the optimized formulation accelerated wound closure, rebalanced collagen deposition, suppressed myofibroblast activation, and markedly prevented pathological fibrosis. Strikingly, it also induced robust de novo hair follicle formation, indicating true functional tissue restoration. Transcriptomic and immunofluorescence analyses further revealed downregulation of pro-fibrotic and inflammatory pathways alongside activation of regenerative signaling, including M2 macrophage polarization and suppression of the M1 phenotype in treated wounds. This study introduces an early vitamin A-based nanocomposite hydrogel with dual anti-scarring and regenerative functions, offering a promising strategy for advanced wound care.

Periodontitis, the sixth most significant global pandemic driven by bacterial biofilms, is characterized by cytotoxic reactive oxygen species (ROS) and histolytic matrix metalloproteinases (MMPs) accumulation, resulting in progressive periodontal destruction. Current therapies are limited by diagnostic inaccuracy, incomplete biofilm elimination, and inadequate tissue regeneration. To address these challenges, an injectable theranostic Ce6@PEG-MoOx-loaded hydrogel through facile construction is proposed, encompassing an intelligent closed-loop for comprehensive periodontitis management. After being injected into periodontal pockets, the hydrogel adheres to tissues and responds to microenvironmental MMPs, realizing on-demand therapeutic release. By integrating photoacoustic imaging, the hydrogel facilitates noninvasive, precise and reproducible measurement of porcine periodontal pocket depths, enabling periodontitis diagnosis and monitoring. Subsequently, released oxygen-vacancy-rich MoOx nanozyme mitigates cellular oxidative stress, generates O2 to enhance Ce6-mediated photodynamic eradication of deep-seated biofilms, and scavenges residual ROS after bactericidal process. Notably, this system avoids off-target ROS generation and photothermal damage, preserving surrounding tissues including dental pulp, thus exhibiting exceptional light-controlled ROS-modulation. Furthermore, released Mo activates the PI3K/AKT pathway to upregulate angiogenic factors, reprograms M2 macrophages polarization, and stimulates osteogenesis of periodontal stem cells. Altogether, this self-adaptive ecosystem integrates diagnosis, monitoring, biofilm debridement, and tissue regeneration, establishing a closed-loop precision therapy for periodontitis with significant clinical potential.

Chronic wounds, such as diabetic foot ulcers, often exhibit lower temperatures due to impaired local circulation, leading to reduced cellular metabolism and delayed healing. This study explores a new strategy to accelerate wound healing by enhancing the cell metabolism of essential amino acids through a "hot spring" mimetic photothermal effect. We engineered an extracellular matrix mimetic nanofiber aerogel co-delivering an eight essential-amino-acid cocktail and photothermally active SrCuSi4O10 bioceramic particles to support chronic wound repair. In vitro, fibroblasts cultured at 25°C versus 37°C showed that physiological temperature preserved the pro-healing bioactivity of the amino-acid treatment with minimal cytotoxicity and was associated with enhanced glutathione redox metabolism. In vivo, the amino acid-loaded aerogel combined with SrCuSi4O10-mediated photothermal therapy accelerated wound closure and improved regenerative outcomes, including increased cellular proliferation, collagen deposition, and neovascularization. Immunohistochemical analysis showed a reduction in neutrophil infiltration, M1 macrophage polarization, and pro-inflammatory cytokines, while increasing M2 macrophage polarization and anti-inflammatory cytokine production, thus shifting the local inflammatory response from pro-inflammatory to regenerative. This approach demonstrates potential as an effective therapeutic option for enhancing the healing of chronic wounds.

Periodontitis is a prevalent chronic inflammatory disease driven by bacterial infection, whose treatment remains challenging due to persistent inflammation and limited tissue regeneration. Here, we developed an injectable and thermosensitive hydrogel (Bi2S3@Gel) composed of hyaluronic acid/PluronicF127 and Bi2S3 nanorods (Bi2S3 NDs), which synergistically combines antibacterial and anti-inflammatory functions. Under near‑infrared (NIR) irradiation, Bi2S3@Gel exhibits excellent photothermal properties. It generates mild hyperthermia while simultaneously amplifying reactive oxygen species (ROS) and depleting glutathione (GSH), leading to effective bacterial eradication. Simultaneously, the hyaluronic acid matrix prolongs local retention, suppresses M1 macrophage polarization, and promotes tissue repair. In vitro studies confirm favorable biocompatibility, potent antibacterial activity, and effective immunomodulation. In vivo, Bi2S3@Gel accelerates diabetic wound healing and promotes periodontal regeneration comparable to minocycline treatment, as evidenced by reduced inflammation, enhanced collagen deposition, and significant alveolar bone restoration. Collectively, Bi2S3@Gel integrates antibacterial, anti‑inflammatory, and regenerative capabilities, offering a promising therapeutic platform for periodontitis and other chronic infectious diseases.

Liver fibrosis, a wound-healing response to chronic injury, can progress to cirrhosis and hepatocellular carcinoma. We investigated Tripartite motif-containing protein 26 (TRIM26) in liver fibrosis and its mechanisms. TRIM26 knockout (Trim26⁻/⁻) mice were generated to study Trim26's role in liver fibrosis. Histological analyses, qPCR, and western blotting were conducted to examine fibrosis markers and macrophage activation. In vitro studies examined macrophage polarization and hepatic stellate cells (HSCs) activation. Co-immunoprecipitation and ubiquitination assays were performed to explore the interaction between TRIM26 and enhancer of zeste homolog 2 (EZH2). TRIM26 expression was significantly downregulated in human cirrhotic tissues and fibrotic mouse livers. In Trim26⁻/⁻ mice, CCl₄- and BDL-induced fibrosis models exhibited exacerbated collagen deposition, elevated α-smooth muscle actin (α-SMA), and type I collagen (Collagen I) expression, whereas AAV-mediated Trim26 restoration markedly ameliorated these pathological features. Transcriptomic and cellular analyses indicated that Trim26 deficiency increased the pro-inflammatory cytokines, activated NF-κB and STAT1 signaling pathways, enhanced M1 macrophage polarization, and increased inflammatory cell infiltration. In vitro experiments confirmed that conditioned medium from Trim26-deficient macrophages significantly promoted α-SMA and collagen expression in HSCs. Mechanistically, TRIM26 interacts with EZH2, inhibiting TRAF6-mediated K48-linked ubiquitination and degradation to maintain EZH2 stability. EZH2, in turn, suppresses STAT1 transcriptional activity by catalyzing H3K27me3 modification on the STAT1 gene chromatin. EZH2 degradation leads to STAT1 upregulation, exacerbating M1 macrophage polarization. Trim26 attenuates liver fibrosis by stabilizing EZH2 and regulating macrophage polarization, which reduces HSC activation.

Injectable, regenerative and anti-infective PEGylated polyglycerol sebacate-modified calcium phosphate cements triggered by berberine and rhBMP-2 for oral bone defect repair.

Bioactive prosthetic interface constructed with cascading multi-nanozyme hydrogel to induce M2 macrophage polarization and heal diabetic bone defects.

An injectable conductive multifunctional hydrogel dressing with synergistic antimicrobial, ROS scavenging, and electroactive effects for the combined treatment of chronic diabetic wounds.

DNMT1-mediated LAMA2 inhibition induces M2 macrophage polarization during prostate cancer progression.

Integrated multi-omics, network pharmacology, and experimental validation reveal that Yinmeikuijie decoction alleviates ulcerative colitis by inhibiting arachidonic acid metabolism.

Exosomes derived from ovarian cancer promote the progression of ovarian cancer through macrophage M2 polarization mediated by the THBS1/TGFBI signaling axis.

A sprayable TQ/Ce6@SAB/F-gel for accelerating wound healing via hypoxia-tolerant photodynamic therapy and immune-metabolic pathway.

Programmed temporal modulation by using a magnetoelectric wound dressing for ultra-fast early-stage wound healing.

Ultraviolet-induced Glycyrrhiza polysaccharide hydrogels with different mechanical strength for wound management.

Adiponectin attenuates atherosclerosis via macrophage polarization-mediated T Cell exhaustion by modulating the NF-κB p65/PI3K/Akt signaling pathway.

TWEAK exacerbates allergic conjunctivitis via PKM2-dependent NF-κB activation and macrophage M1 polarization.

Kielin/chordin-like protein(KCP) deficiency exacerbates doxorubicin-induced myocardial injury by promoting macrophage M1 polarization through autophagy inhibition.

IL-33/ST2 signaling promotes intrahepatic cholangiocarcinoma through reprogramming macrophage polarization via MAPK pathway.

Glutamine metabolites promote the progression of cervical cancer by inducing M2 macrophage polarization.

Self-supported DNA hydrogel facilitates microenvironment remodeling and cartilage repair to prevent osteoarthritis progression via an ambidextrous strategy.