Yandong Mu

1. Cutaneous wound healing is a dynamic and highly coordinated process in which early inflammation must be resolved in a timely manner to permit re-epithelialization, granulation tissue formation, ...

Precise adhesion of bone fragments and robust bone regeneration are both essential for successful fracture healing, yet existing hydrogel adhesives rarely achieve controllable fixation and sustained osteogenesis simultaneously. Herein, we report a polyphenol‐engineered ultrasound‐responsive injectable hydrogel for fracture fixation and bone regeneration. The hydrogel is composed of dihydrocaffeic acid‐modified chitosan, gelatin methacryloyl, a 2D sonosensitizer (PGO‐Fe) constructed from polydopamine‐mediated ferroferric oxide‐decorated reduced graphene oxide, and polydopamine‐modified hydroxyapatite (PHA). The hydrogel initially forms reversible, shape‐adaptable adhesion to bone via catechol‐mediated noncovalent interactions. Upon high‐intensity ultrasound (HUS), PGO‐Fe enhances sonodynamic activity through Fe(III)/Fe(II) redox conversion, triggering secondary covalent crosslinking and enabling a controllable transition from compliant adhesion to rigid fixation. Polyphenolic components confer reactive oxygen species‐scavenging capacity and promote macrophage polarization toward the M2 phenotype, creating a favorable regenerative microenvironment. Under low‐intensity ultrasound (LUS), the hydrogel activates Piezo1‐mediated calcium influx, thereby enhancing osteogenic differentiation. In vivo, this system achieves nearly complete defect bridging and mechanical performance comparable to wire fixation in rat calvarial and rabbit ulna models. This work provides a minimally invasive strategy that integrates controlled fixation, immunomodulation, and mechanically enhanced osteogenesis for complex fracture treatment.

Background: Bone regeneration unfolds through sequential inflammatory, reparative, and remodeling phases, with macrophages functioning as pivotal regulators across these stages. Accumulating evidence identifies macrophage-derived exosomes (M-Exos) as key mediators of intercellular communication that dynamically shape the bone healing microenvironment. Main body: This review synthesizes current evidence on the spatiotemporal roles of M-Exos during bone healing and discusses how donor macrophage states may shape vesicle function across inflammatory, reparative, and remodeling phases. The discussion elucidates how dynamic macrophage functional states shape exosomal cargo and biological activity during distinct stages of repair. Concurrently, emerging engineering strategies to harness and enhance M-Exos’ regenerative functions are evaluated, including exosome engineering, therapeutic cargo optimization, and biomaterial-assisted delivery approaches. In addition, this paper scrutinizes the translational landscape of M-Exos, emphasizing their potential as a cell-free therapeutic modality for bone tissue engineering while outlining key challenges critical for clinical implementation. Conclusions: By integrating the spatiotemporal functions of macrophage-derived exosomes (M-Exos) and single-cell-resolved landscapes of macrophage functional states, this review delineates the mechanistic links among macrophage state transitions, M-Exo cargo profiles, and regenerative outcomes across distinct phases of bone healing. It further provides a theoretical basis for developing stage-adaptive and functionally tunable M-Exo–based strategies for bone regeneration.

The repair of irregular periodontal bone defects remains a formidable clinical challenge due to the complex oral microenvironment, which demands that therapeutic materials integrate early antibacterial and anti-inflammatory effects with sustained osteogenic support. Herein, we present an injectable multifunctional double-cross-linked hydrogel (GGCM) based on gelatin and chondroitin sulfate (CS), incorporating Mg/Mn-based nanozymes (MPM NZs) for photothermal therapy of periodontitis. MPM NZs were first synthesized via chemical deposition of nano-MnO₂ onto mesoporous MgO nanoparticles and subsequently incorporated into a dual-cross-linked network formed by glycidyl methacrylate-modified gelatin and oxidized chondroitin sulfate (OCS) through sequential Schiff base and photopolymerization reactions. The resulting GGCM hydrogel exhibited a favorable microporous architecture, robust physicochemical properties, and excellent injectability to fill irregular periodontal pockets. Notably, MPM NZs endowed the hydrogel with potent photothermal antibacterial activity (>95%), superoxide dismutase (SOD)- and catalase (CAT)-mimetic activities for reactive oxygen species (ROS) scavenging, and the sustained release of bioactive Mg²⁺ and Mn²⁺ ions for immunomodulation and osteogenesis. Importantly, GGCM enables a time-sequential regenerative therapeutic cascade comprising rapid periodontal pathogen elimination upon NIR irradiation, subsequent anti-inflammatory immunomodulation via M2 macrophage polarization, and continuous osteogenic promotion and alveolar bone resorption reduction. Collectively, this multifunction-integrated MPM NZ-enhanced double-cross-linked hydrogel exhibits promising potential for periodontal bone regeneration, positioning it as a highly attractive photothermal therapeutic strategy for periodontitis and even other complex infectious bone defects.

Temporomandibular joint osteoarthritis (TMJOA) is a disease that affects the TMJ and is associated with degenerative changes in the articular cartilage. Fibroblast-like synoviocytes (FLSs) have been found to contribute to osteoarthritis. Here, we aim to investigate the role of METTL3-mediated FLS senescence in the TMJOA process. TMJOA model rats were successfully generated, displaying typical structural and inflammatory alterations, and primary FLSs were isolated from monosodium iodoacetate (MIA)-induced TMJOA rats; these FLSs were accompanied by increased senescence, attenuated mitophagy, and upregulated METTL3. FLSs from TMJOA rats also induced cartilage degradation. Mechanistically, METTL3 silencing can increase PINK1 expression by increasing its RNA stability through m⁶A modification. In addition, we found that METTL3 silencing could delay cellular senescence and promote mitophagy by upregulating PINK1 in bleomycin (BLM)-induced hFLSs. Senescent FLSs can also accelerate pathological progression and cartilage degradation in Sprague-Dawley (SD) rats. This study revealed that METTL3 silencing could suppress the senescence of FLSs and promote mitophagy by mediating m⁶A modification to upregulate PINK1 during TMJOA progression, which might provide a theoretical basis for TMJOA therapy.

Background: Osteoradionecrosis of the jaw (ORNJ) is a common complication following radiotherapy for head and neck cancer. Thus, this study aimed to explore the effects of active components in Lycium barbarum on ORNJ through network pharmacology and to conduct experimental verification to identify potential therapeutic targets. Methods: The main active ingredients in Lycium barbarum (Gouqi), a traditional Chinese herbal medicine, was used in this study. After identifying ferroptosis-related genes associated with ORNJ, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and constructed an interaction network. A molecular interaction force analysis was then performed on eight binding conformations to identify the optimal conformation with the lowest binding free energy. We established a model of ORNJ in Sprague-Dawley (SD) rats and administered oral Lycium barbarum glycopeptide (LbGP) to the experimental group. Moreover, reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemical staining techniques were then employed to detect the mRNA and protein levels of various relevant cytokines. Results: Based on network pharmacology predictions, this study identified three potential active components in Lycium barbarum, namely β-sitosterol, glycitein, and quercetin. The possible effects of these components in the treatment of ORNJ were analyzed. Seven hub genes related to ferroptosis and ORNJ were identified, and LbGP was selected for in vivo verification. The expression levels of TP53, EGFR, IL-6, and TNF were significantly altered in the LbGP group compared to the untreated group, as revealed by the qPCR, ELISA, and immunohistochemistry assays. Conclusion: The use of Lycium barbarum extract may exert therapeutic effects on mandible injury following ORNJ by regulating the expression of TP53, EGFR, IL-6, and TNF.

Background Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy with poor prognosis and low five-year survival rates. Ferroptosis, an iron-dependent form of cell death, has emerged as a potential factor in cancer therapy. This study aimed to identify differentially expressed genes (DEGs) associated with HNSCC, ferroptosis, and radiotherapy, and to develop a diagnostic model to establish novel biomarkers, early diagnosis and individualized therapy. Methods We analyzed TCGA-HNSCC, GSE6631, and GSE107591 datasets to identify Ferroptosis- and Radiotherapy-Related Differentially Expressed Genes (F&RRDEGs).Ferroptosis & radiotherapy scores were calculated, followed by immune infiltration and immunotherapy analyses. A Cox prognostic model was evaluated using nomograms, calibration curves, and decision curve analysis. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used for experimental validation. Results 11 F&RRDEGs were identified classifying two subtypes related to HNSCC.Significant differences were found in immune cell infiltration and immunophenoscore in CTLA4 and PD1/PD-L1/PD-L2 + CTLA4 between high and low ferroptosis & radiotherapy scores(F&Rs) groups. The 1-year calibration curve of the prognostic risk model showed better and more accurate performance and performance for the five-year prediction. RT-qPCR identified significant differences in the genes ALOX12, EMP1, PIM1, and CA9 between the control and HNSCC groups, with WB confirming radiotherapy-induced upregulation of VDAC1/TFRC (pro-ferroptosis) and downregulation of GPX4/SLC7A11/FTH1 (anti-ferroptosis) in irradiated HNSCC cells. Conclusion ALOX12, EMP1, PIM1, and CA9 exhibited promising potential as diagnostic biomarkers. This study applies immune infiltration analysis to HNSCC research, offering fresh perspectives on patient-specific treatment plans, and accelerating the creation of focused therapies.