Yufeng Zhang

Hyperlipidemia compromises implant integration, but the molecular mechanisms linking dyslipidemic environments to the biomaterial performance remain largely unknown. Here, we identify interfacial charge remodeling as a key regulator of the protein-mediated cell adhesion. Fibronectin (FN) is shown to govern endothelial attachment under hyperlipidemic conditions through charge-dependent interactions with the material surfaces. Molecular dynamics simulations reveal that the local charge distribution governs FN adsorption and conformational stability, while total internal reflection fluorescence (TIRF) single-molecule tracking demonstrates that charged adhesion domains regulate FN residence and adhesion stability in lipoprotein-rich environments. Deletion of negatively charged residues stabilizes FN–surface interactions, attenuates lipid-dependent disruption of adhesion signaling, and enhances endothelial responses. Similar charge-dependent behavior is observed on poly(lactic acid) (PLA), extending this interfacial charge remodeling from inorganic to organic biomaterials. These findings establish interfacial charge as a molecular determinant of implant integration under hyperlipidemic conditions and provide a general strategy for designing metabolism-responsive biomaterials.

Periodontal disease is a highly prevalent chronic inflammatory condition worldwide, significantly impairing patients’ quality of life and imposing a substantial burden on healthcare systems. In recent years, significant progress has been made in the immunopathogenesis of periodontal diseases, highlighting the crucial role of immune regulation in restoring periodontal homeostasis and promoting tissue regeneration. Meanwhile, the rapid development of osteoimmunology in tissue engineering has provided a theoretical framework for elucidating periodontal bone regeneration from the perspective of immune–bone coupling and offered new insights into therapeutic optimization. This review systematically summarizes the osteoimmunological basis of periodontal bone regeneration, focusing on how the physicochemical properties of biomaterials modulate the periodontal osteoimmune microenvironment. Recent progress in osteoimmunomodulatory biomaterials for periodontal bone regeneration is summarized, highlighting strategies involving physical and chemical modifications, bioactive molecule enhancements, as well as cell- and cell-derived product–based modifications. Considering the complexity of the periodontal immune microenvironment, advances in stimuli-responsive biomaterials for immune modulation and their roles in periodontal bone regeneration are further discussed. Finally, key challenges in material design and clinical translation of osteoimmunomodulatory biomaterials are addressed, and future perspectives are proposed to provide theoretical guidance for the rational design and translational development of immunomodulatory biomaterials for periodontal bone regeneration.

Mineralization is a critical process in the formation of hard tissues such as bones and teeth, yet the cellular mechanisms underlying this process remain incompletely understood. To address this, we constructed a comprehensive single-cell atlas of tooth development, integrating data from 261,929 cells across 15 projects and encompassing both odontogenesis and amelogenesis. We developed a novel algorithm, TrajDTW, to identify genes with concordant trajectory dynamics across these large-scale datasets, allowing us to detect robust developmental signals. To define a shared mineralization trajectory architecture, we then integrated our tooth atlas with a previously constructed bone atlas. Applying TrajDTW to this combined resource revealed common molecular pathways governing the formation of distinct hard tissues, including bone, enamel, and dentin. Furthermore, cross-species analysis between human and mouse data uncovered cross-species conserved mesenchymal/odontoblast programs. This study provides an unprecedented resource for developmental biology and defines a molecular framework for mineralization that is shared across tissues and species.

Objectives: Adequate horizontal bone width is essential for successful implant placement and long‐term stability. This study aimed to compare the outcomes of two techniques for horizontal alveolar ridge augmentation: the horizontal platelet‐rich fibrin (H‐PRF) bone block technique and the Sausage technique. Materials and Methods: Fifty patients, presenting 63 tooth sites, were enrolled between 2023 and 2025. Twenty five patients were treated with H‐PRF bone block technique (H‐PRF group), while 25 patients were treated using the “Sausage” technique (Sausage group) for horizontal bone augmentation. The bone width gain, bone stability rate, and bone volume change at 6 months after surgery were quantified by measurements through cone beam computed tomography (CBCT) scans. Furthermore, the correlation between bone width gain, bone stability rate, and gender, defect site, and bone defect type was analyzed. The complication rates were also recorded. Results: The H‐PRF group demonstrated significantly greater horizontal bone gain at the crestal level compared with the Sausage group (0 mm level: 2.85 ± 4.05 mm vs. 0.79 ± 2.35 mm; p = 0.043), while no significant differences were observed at 2, 4, 6, 8 mm levels ( p > 0.05). The bone stability rate was 63.21% ± 27.67% for the H‐PRF group and 63.88% ± 16.64% for the Sausage group ( p = 0.791). Both bone width gain and bone stability rate were not associated with gender or defect site. However, defect type showed a significant association with horizontal bone width gain at the most apical levels (6 and 8 mm). Conclusions: The H‐PRF bone block technique achieved comparable bone augmentation outcomes to the Sausage technique; this technique represents a promising approach that may be considered for horizontal bone augmentation.

During homeostasis, osteocyte apoptosis is typically associated with bone loss through enhanced osteoclast recruitment and bone resorption. However, whether apoptotic osteocytes also regulate bone formation remains elusive. Here we report that conditional deletion of Mdm2 , an E3 ubiquitin ligase regulating cell survival, causes osteocyte apoptosis but paradoxically results in a marked increase in bone mass attributed to up-regulated osteogenic activity. Single-cell RNA sequencing reveals enhanced osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) in conditional knockout mice, with enrichment of cellular calcium related pathways. Mechanistically, apoptotic vesicles (apovs) from Mdm2 -deleted osteocytes are engulfed by BMSCs. TRPM8, a calcium channel protein, is enriched in osteocyte-derived apovs and transported into BMSCs, thereby promoting osteoblastic differentiation. Additionally, pharmacological inhibition of TRPM8 attenuates the high bone mass phenotype in conditional knockout mice. Therefore, Mdm2 deletion in osteocytes leads to osteocyte apoptosis, which enhances bone formation through communicating with BMSCs via TRPM8-enriched apovs. Our findings underscore the pivotal role of osteocytes in bone homeostasis and unveil a previously unrecognized mechanism whereby osteocyte apoptosis stimulates osteogenesis through affecting the fate of BMSCs in a TRPM8-mediated paracrine mechanism.

Aim: Platelet‐rich fibrin (PRF) has been widely utilized in oral and craniofacial tissue regeneration owing to its autologous origin and favorable biological properties. However, the limited structural stability of conventional PRF restricts its space‐maintaining capacity and osteogenic performance in guided bone regeneration (GBR). To address these shortcomings, a novel heat‐modified PRF (Heat‐H‐PRF) was developed to improve the structural stability and osteogenic performance of PRF. Methods: Human PRF was subjected to brief thermal treatment to generate Heat‐H‐PRF. Material microstructure was examined by scanning electron microscopy. In vitro biocompatibility and osteogenic potential were assessed using MC3T3‐E1 preosteoblasts through analyses of cell adhesion, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenic marker expression in comparison to a commercially available collagen membrane. Bone regeneration was also evaluated in vivo using a murine critical‐size calvarial defect model, with micro‐computed tomography, histological staining, and immunohistochemical analysis performed at 4 weeks post‐implantation. Results: Heat‐H‐PRF demonstrated excellent cytocompatibility and significantly enhanced osteoblast‐lineage cell proliferation, spreading, osteogenic differentiation, and mineralized matrix formation in vitro compared with collagen membrane. In a murine calvarial defect model, Heat‐H‐PRF resulted in significantly greater new bone volume, bone surface, and collagen deposition, accompanied by stronger expression of osteogenic markers Runx2, Osterix, osteocalcin, and collagen 1. Furthermore, the improved structural integrity of Heat‐H‐PRF suggests enhanced handling stability and potential space‐maintaining properties, which may contribute to improved bone regeneration. Conclusion: Heat‐modified PRF represents a simple and autologous biomaterial with improved handling properties and enhanced osteogenic potential. These findings suggest that Heat‐H‐PRF may serve as a promising adjunctive membrane‐like scaffold for guided bone regeneration.

Background: Extracellular vesicles (EVs), especially exosomes, are nanoparticles increasingly recognized as key regulators of intercellular communication in both physiological and pathological aspects. Despite rapid progress, inconsistencies in nomenclature, isolation, and characterization continue to restrict translational advancement. This review aims to offer a comprehensive synthesis of EV biology, with a focus on biogenesis, molecular composition, heterogeneity, and methodological considerations for isolation and characterization. Methods: A narrative review of the literature was performed, assessing historical progress, molecular mechanisms regulating EV biogenesis and payload selection, and existing experimental methods for EV isolation and analysis. Moreover, a comparative analysis of classical and emerging isolation approaches was conducted. Results: EVs are shown to carry diverse bioactive cargo, such as proteins, lipids, and nucleic acids, allowing modulation of cascades implicated in immunity, tissue regeneration, and disease progression. Considerable variability exists across EV subpopulations, complicating categorization and functional attribution. Isolation techniques demonstrate unique trade‐offs between scalability, yield, purity, and functional integrity, with no universally optimal strategy. Crucially, methodological selection is highly based on downstream applications, with therapeutic and diagnostic uses necessitating fundamentally varying performance criteria. Conclusion: EVs serve as dynamic signaling systems with significant therapeutic and diagnostic potential. Advancing the discipline needs standardized techniques, enhanced classification platforms, and context‐specific optimization of isolation approaches. A deeper comprehension of EV biology and methodological rigor will be necessary to unravel their full application in precision medicine.