Macrophages have been found to regulate the effects of biomaterials throughout the entire tissue repair process as an antigen-presenting cell. As a well-defined osteoconductive biomaterial for bone defect regeneration, tricalcium phosphate (TCP) has been found to facilitate a favourable osteoimmunomodulatory response that can shift macrophage polarization towards the M2 phenotype. In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Furthermore, the NF-κB pathway in macrophages was significantly downregulated through stimulation of TCP, suggesting a potential interaction between EZH1 and the NF-κB pathway. Utilizing gene knock-down therapy in macrophages, it was found that depletion of EZH1 induced M2 macrophage polarization but did not downregulate NF-κB. When the NF-κB pathway was inhibited, the expression of EZH1 was significantly downregulated, suggesting that the inhibition of EZH1 may be regulated by the NF-κB pathway. These novel findings provide valuable insights into a potential gene target system that controls M2 macrophage polarization which ultimately favours a microenvironment suitable for bone repair.

Purpose: As the population ages, there is an increased risk of fracture and morbidity diseases associated with aging, such as age-related osteoporosis and other bone diseases linked to aging skeletons. Results: Several bone-related cells, including multipotent bone mesenchymal stem cells, osteoblasts that form bone tissue, and osteoclasts that break it down, are in symbiotic relationships throughout life. Growing evidence indicates that epigenetic modifications of cells caused by aging contribute to compromised bone remodeling and lead to osteoporosis. A number of epigenetic mechanisms are at play, including DNA/RNA modifications, histone modifications, microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), as well as chromatin remodeling. Conclusion: In this review, we summarized the epigenetic modifications of different bone-related cells during the development and progression of osteoporosis associated with aging. Additionally, we described a compensatory recovery mechanism under epigenetic regulation that may lead to new strategies for regulating bone remodeling in age-related osteoporosis.

Oral diseases, encompassing conditions such as periodontitis, head and neck squamous cell carcinoma, pulpitis, and mucosal infections, remain a major global health burden due to their high prevalence and complex, multifactorial pathophysiology. The unique anatomical structure of the oral cavity, together with persistent microbial challenges and dynamic immune responses, imposes substantial limitations on conventional drug delivery strategies. Biomimetic cell membrane-based materials have recently emerged as a promising class of delivery platforms, leveraging natural biological interfaces to confer inherent biocompatibility, immune evasion, prolonged circulation, specific targeting, and biofilm-interactive capabilities. These features position them as a transformative approach for improving therapeutic precision and efficacy in oral disease management. In this review, we provide a systematic and materials-oriented overview of biomimetic cell membrane-based drug delivery systems. Specifically, we discuss: (1) the biological sources, classification, and physicochemical properties of membrane-coated systems, along with their fabrication and engineering strategies; (2) the mechanistic basis of targeting, immune modulation, and nanobiointerface interactions, and their applications across representative oral diseases; and (3) current challenges, including scalable manufacturing, functional controllability, biosafety, and clinical translation. Furthermore, we highlight emerging directions such as stimuli-responsive membrane systems and multifunctional integrated platforms, aiming to provide a conceptual framework for the rational design and clinical advancement of biomimetic drug delivery systems in complex disease settings.

Dental caries, primarily caused by Streptococcus mutans (S. mutans), remains a significant global health challenge. Conventional treatments often disrupt commensal oral flora, necessitating targeted antimicrobial strategies. This study investigated L‑serine-O-sulfate (LSOS), a substrate analog of glutamate racemase (MurI), as a potential agent for interfering with S. mutans UA159 virulence. Computational docking predicted LSOS binding to MurI, while circular dichroism spectroscopy confirmed LSOS-induced structural perturbations in recombinant MurI. LSOS exhibited concentration-dependent bactericidal effects, with 5.0 mM completely suppressing growth and 2.5 mM significantly extending doubling time (11.37 hrs vs. 5.68 hrs in controls). Transmission electron microscopy revealed progressive ultrastructural damage, characterized by membrane blebs and cell wall disintegration. Biofilm formation was severely impaired, with 63 % reduction in biomass and significant disruption of extracellular matrix integrity. Microarray-based gene expression analysis identified 119 differentially expressed genes, predominantly downregulated (111/119), affecting translation machinery, metabolic pathways, and transmembrane transport. Biosafety evaluation in L929 fibroblasts showed reduced proliferation (67.59 % of control at 2.5 mM after 48 hrs) with both G1-phase reduction and S-phase cell cycle accumulation. Caenorhabditis elegans demonstrated uncompromised survival and early development at concentrations <10 mM, with developmental toxicity emerging only at higher doses (≥20 mM). These findings establish LSOS as a promising anti-virulence agent targeting MurI in S. mutans UA159, with favorable biosafety profiles that warrant further investigation for dental caries prevention and treatment.