Shengao Qin

Bisphosphonates (BPs) are cornerstone therapeutic agents for the management of metabolic bone disorders and skeletal complications associated with malignant tumors. However, their long-term administration is accompanied by the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ). In recent years, the pathogenesis of BRONJ has remained a major focus at the intersection of osteoimmunology and oral medicine. This review systematically summarizes the latest advances in the understanding of BRONJ pathogenesis, including the direct disruption of osteoclast differentiation and bone remodeling coupling by bisphosphonates, the systemic reprogramming of immune cell subsets and inflammatory signaling pathways, the multifaceted suppression of angiogenesis and the endothelial–stromal–immune axis, and the toxic impairment of oral soft tissue repair capacity. Building upon these mechanistic insights, we further discuss the modifying and synergistic effects of local oral risk factors, microbial dysbiosis, systemic comorbidities, and genetic susceptibility on the initiation and progression of BRONJ. Furthermore, emerging therapeutic strategies targeting these pathogenic mechanisms are highlighted, including restoration of small GTPase prenylation through modulation of metabolic pathways, reconstruction of T-cell subset homeostasis via immunomodulatory approaches, enhancement of local vascularization through pro-angiogenic interventions, and preservation of soft tissue barrier integrity. Collectively, this review provides a comprehensive and multidimensional overview of the pathological landscape of BRONJ and offers a theoretical framework for clinical risk stratification and the development of personalized prevention and treatment strategies.

Aging is a major risk factor for impaired bone-defect healing, and dysregulation of the immune microenvironment, especially macrophage dysfunction, is closely linked to this process. Interleukin-34 (IL-34) plays a crucial role in macrophage biology; however, its role in aging-related bone-defect healing remains elusive. Herein, young and aged male C57BL/6 mice were utilized to establish a tibial bone defect model. Microcomputed tomography, histological staining, flow cytometry, RNA sequencing and in vitro cell experiments were conducted to explore the role and mechanism of action of IL-34 in aging-impaired bone healing. Aging markedly decreased bone mass, inhibited osteogenic differentiation and impaired bone defect healing in mice. Moreover, aging reduces macrophage numbers at bone defects and suppresses M2 polarization, with the drop likely driven by recruitment, survival or proliferation defects rather than impaired recruitment exclusively. IL-34 was a key differentially expressed gene that was downregulated in aged mice, which was further confirmed at the protein level. Furthermore, aging decreased IL-34 secretion by macrophages and impaired macrophage proliferation and M2 polarisation. Thus, aging impairs tibial bone-defect healing by downregulating IL-34 expression, decreasing macrophage infiltration, and inhibiting M2 polarisation. Furthermore, IL-34 acts as a pro-reparative cytokine that promotes bone healing by regulating macrophage function, suggesting its role as a potential therapeutic target for enhancing age-related bone repair.

Bone tissue engineering, as an important branch of regenerative medicine, integrates multidisciplinary knowledge from cell biology, materials science, and biomechanics, aiming to develop novel biomaterials and technologies for functional repair and regeneration of bone tissue. Hydrogels are among the most commonly used scaffold materials; however, conventional hydrogels exhibit significant limitations in physical properties such as strength, tensile strength, toughness, and fatigue resistance, which severely restrict their application in load-bearing bone defect repair. As a result, the development of high-strength hydrogels has become a research hotspot in the field of bone tissue engineering. This paper systematically reviews the latest research progress in this area: First, it delves into the physicochemical characteristics of high-strength hydrogels at the molecular level, focusing on core features such as their crosslinking network structure, dynamic bonding mechanisms, and energy dissipation principles. Next, it categorically summarizes novel high-strength hydrogel systems and different types of biomimetic hydrogels developed based on various reinforcement strategies. Furthermore, it provides a detailed evaluation of the application effects of these advanced materials in specific anatomical sites, including cranial reconstruction, femoral repair, alveolar bone regeneration, and articular cartilage repair. This review aims to provide systematic theoretical guidance and technical references for the basic research and clinical translation of high-strength hydrogels in bone tissue engineering, promoting the effective translation of this field from laboratory research to clinical application.

Wound healing progresses through three distinct stages: inflammation, proliferation, and remodeling. Immune regulation is a central component throughout, crucial for orchestrating inflammatory responses, facilitating tissue repair, and restraining scar tissue formation. Elements such as mitochondria, reactive oxygen species (ROS), macrophages, autophagy, ferroptosis, and cytokines collaboratively shape immune regulation in this healing process. Skin wound dressings, recognized for their ability to augment biomaterials’ immunomodulatory characteristics via antimicrobial, antioxidative, pro- or anti-inflammatory, and tissue-regenerative capacities, have garnered heightened attention. Notwithstanding, a lack of comprehensive research addressing how these dressings attain immunomodulatory properties and the mechanisms thereof persists. Hence, this paper pioneers a systematic review of biomaterials, emphasizing immune regulation and their underlying immunological mechanisms. It begins by highlighting the importance of immune regulation in wound healing and the peculiarities and obstacles faced in skin injury recovery. This segment explores the impact of wound metabolism, infections, systemic illnesses, and local immobilization on the immune response during healing. Subsequently, the review examines a spectrum of biomaterials utilized in skin wound therapy, including hydrogels, aerogels, electrospun nanofiber membranes, collagen scaffolds, microneedles, sponges, and 3D-printed constructs. It elaborates on the immunomodulatory approaches employed by these materials, focusing on mitochondrial and ROS modulation, autophagic processes, ferroptosis, macrophage modulation, and the influence of cytokines on wound healing. Acknowledging the challenge of antibiotic resistance, the paper also summarizes promising plant-based alternatives for biomaterial integration, including curcumin. In its concluding sections, the review charts recent advancements and prospects in biomaterials that accelerate skin wound healing via immune modulation. This includes exploring mitochondrial transplantation materials, biomaterial morphology optimization, metal ion incorporation, electrostimulation-enabled immune response control, and the benefits of composite materials in immune-regulatory wound dressings. The ultimate objective is to establish a theoretical foundation and guide future investigations in the realm of skin wound healing and related materials science disciplines.

Introduction: Immune cells are dynamic in the inflammatory environment and play a key role in eradicating periodontal pathogens, modulating immune responses, and instigating tissue destruction. Identifying specific immune cell phenotypes associated with periodontitis risk is essential for targeted immunotherapeutic interventions. However, the role of certain specific immune cell phenotypes in the development of periodontitis is unknown. Mendelian randomization offers a novel approach to reveal causality and address potential confounding factors through genetic instruments.Methods: This two-sample Mendelian randomization study assessed the causal relationship between 731 immune cell phenotypes and periodontitis using the inverse variance weighting method with the GWAS catalog genetic database. Methodological robustness was ensured through Cochran’s Q test, MR-Egger regression, MR-PRESSO, and Leave-One-Out analysis.Results: 14 immune cell phenotypes showed potential positive causal associations with periodontitis risk (p < 0.05), suggesting an increased risk, while 11 immune cell phenotypes exhibited potential negative causal associations (p < 0.05), indicating a reduced risk. No significant heterogeneity or pleiotropy was observed.Conclusion: This study underscores certain immune cell types as potential periodontitis risk biomarkers, laying a theoretical foundation for future individualized treatment and precision medicine development.

Background: Targeted therapy for Sjögren’s syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets.Methods: We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets.Results: Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56–3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04–3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins.Conclusion: Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.

Aloe vera is a kind of herb rich in polysaccharides. Acemannan (AC) is considered to be a natural polysaccharide with good biodegradability and biocompatibility extracted from Aloe vera and has a wide range of applications in the biomedical field due to excellent immunomodulatory, antiviral, antitumor, and tissue regeneration effects. In recent years, clinical case reports on the application of AC as a novel biomedical material in tissue regenerative medicine have emerged; it is mainly used in bone tissue engineering, pulp–dentin complex regeneration engineering, and soft tissue repair, among other operations. In addition, multiple studies have proved that the new composite products formed by the combination of AC and other compounds have excellent biological and physical properties and have broader research prospects. This paper introduces the preparation process, surface structure, and application forms of AC; summarizes the influence of acetyl functional group content in AC on its functions; and provides a detailed review of the functional properties, laboratory studies, clinical cutting-edge applications, and combined applications of AC. Finally, the current application status of AC from basic research to clinical treatment is analyzed and its prospects are discussed.