Piezoelectric hydrogels are a class of novel biomaterials fabricated by integrating piezoelectric materials with conventional hydrogel networks. Endowed with piezoelectric properties, they are capable of converting mechanical stimuli into bioelectrical signals that orchestrate tissue regeneration. By utilizing the microelectric fields derived from the piezoelectric effect to actively regulate cellular behaviors, they provide a novel strategy for achieving functional tissue repair. This review systematically delineates their application potential in promoting oral mucosal healing, periodontal and peri-implant bone regeneration, and jawbone defect repair. It further explores the biological mechanisms underlying tissue regeneration and the critical factors governing material performance. Additionally, it analyzes current challenges in mechanistic elucidation, material property matching, and preclinical evaluation, and provides an outlook on future development directions.
Biomineralization is the biological process by which organisms produce inorganic minerals within a regulated microenvironment through the coordinated actions of cells and the extracellular organic matrix. It underpins the formation of mineralized tissues such as bone, teeth, and shells. During this process, mineral nucleation, crystal growth, and hierarchical assembly are tightly regulated by specific matrix proteins. In recent years, functional amyloid proteins have attracted considerable attention for their regulatory role in biomineralization due to their unique structure, remarkable mechanical stability, and self-assembly capability. Increasing evidence indicates that functional amyloid proteins, together with their intrinsically disordered precursor proteins, play critical roles in controlling mineral nucleation, crystal growth, and the hierarchical organization of mineral phases in vivo. Although amyloid proteins are best known for their association with neurodegenerative diseases such as Alzheimer's disease, their unique self-assembly behavior has also opened new opportunities in biomaterials, regenerative medicine, and nanotechnology. This review systematically summarizes both classical and non-classical theories of biomineralization, discusses the structural characteristics of amyloid proteins and the molecular mechanisms underlying amyloid-mediated mineralization, and highlights recent advances in the application of amyloid proteins for the biomimetic regeneration of mineralized tissues, particularly bone and dental hard tissues.
The repair and reconstruction of tissue damage and degenerative diseases pose significant clinical challenges. Traditional biomaterials provide only static support and fail to adapt to the dynamic pathological microenvironment of tissue repair. In contrast, stimuli-responsive biomaterials can sense endogenous biochemical signals and exogenous physical stimuli, and achieve precise spatiotemporal regulation through dynamic changes in structure and function, making them a research hotspot in regenerative medicine. This article systematically elaborates the core mechanisms of stimuli-responsive biomaterials in tissue repair and regeneration, including dynamic mechanical support, controlled release of bioactive molecules, regulation of cellular behaviors, and remodeling of the inflammation-immunity-angiogenesis microenvironment. According to the types of triggering signals, the design principles and recent advances of materials responsive to pH, temperature, light, ultrasound, magnetic fields, and multiple stimuli are discussed. It also summarizes their application status in bone tissue repair, soft tissue repair, and targeted tumor therapy. Furthermore, it analyzes key issues in clinical translation, such as response specificity, biosafety, and large-scale preparation, and discusses future development directions, including interdisciplinary integration and intelligent closed-loop regulation. Stimuli-responsive biomaterials provide new strategies for precise and personalized tissue repair and regeneration, with significant basic research value and clinical translation potential.
Early enamel caries is characterized by mineral loss beneath a relatively intact surface. Because mature enamel lacks ameloblasts and endogenous regenerative capacity, therapeutic goals should extend beyond surface mineral deposition to subsurface mineral recovery, restoration of crystal orientation and hierarchical organization, and durable mechanical function. Recent strategies based on calcium-phosphate ionic or pre-nucleation clusters, amorphous calcium phosphate precursors, amelogenin-derived peptides, and other organic templates have improved precursor stabilization and the regulation of ordered crystallization. Tooth-surface functionalization, wet adhesion, pH-responsive release, and targeted antimicrobial systems are also promoting a transition from the simple combination of anticaries and remineralizing functions toward their spatial and temporal coordination. Nevertheless, most available evidence has been obtained from simplified in vitro demineralization or monospecies biofilm models, while repair remains largely confined to micrometer-scale surface layers. Robust evidence is still lacking for mineral recovery throughout clinically representative subsurface lesions, reconstruction of enamel rod/interrod architecture and interfacial continuity, and resistance to recurrent acid challenge, wear, and fatigue. Nonselective antimicrobial interventions may additionally disrupt oral microbial ecology. This expert perspective summarizes advances in surface mineral deposition, subsurface repair, structural and functional reconstruction, and antimicrobial and ecological regulation, while examining the major barriers to clinical translation. Future studies should employ clinically relevant subsurface caries lesions and multispecies biofilm models, integrate lesion-responsive activation and durable material retention with selective virulence control, and establish an evaluation framework linking mineralization depth, structural continuity, and long-term function. The central objective of enamel caries prevention and remineralization is to restore mineral within deep subsurface lesions and rebuild an enamel-continuous, hierarchically organized, and durable structure without compromising oral microbial homeostasis.
Antimicrobial peptides (AMPs) have become a major focus in the development of novel antimicrobial agents due to their broad-spectrum antimicrobial properties and extremely low risk of inducing resistance. Traditional AMP design strategies have relied primarily on the isolation and extraction of natural products, along with limited sequence modifications, which has greatly restricted the discovery of new candidate molecules and led to inefficient in vitro screening processes. With rapid advancements in artificial intelligence (AI), significant breakthroughs have been achieved in the virtual screening of AMPs, preliminary prediction of antibacterial activity, de novo design of peptide sequences, and targeted optimization of peptide structures and functions, thereby significantly shortening research timelines and reducing overall development costs. This article systematically reviews the core features of mainstream antimicrobial peptide databases and the fundamental mechanisms of commonly used AI algorithms, and further elaborates on feasible strategies for applying AI to antimicrobial peptide screening, design, and structural optimization. At the same time, it identifies key bottlenecks in current research, such as the lack of standardized datasets, immature in vivo evaluation systems, and insufficient interdisciplinary collaboration. This review provides valuable insights and theoretical support for the subsequent research, translational development, and clinical application of next-generation antimicrobial peptides.
To investigate the anti-biofouling effect of a polymer coating that combines cell membrane-mimetic phosphorylcholine groups and benzophenone (BP) photoresponsive groups on polymethyl methacrylate (PMMA) denture base material.
Methods
A photoreactive monomer containing BP groups, 4- (3-methacryloyloxy-2-hydroxypropyloxy) benzophenone (MHPBP), was synthesized and copolymerized with cell membrane-mimetic 2-methacryloyloxyethyl phosphorylcholine (MPC) via free-radical polymerization to prepare photoreactive three PMH polymers with different MPC/MHPBP molar ratios (9∶1, 8∶2, 7∶3). Coatings were constructed on PMMA surfaces by dip-coating followed by UV irradiation. The optimal formulation (PMH82) was selected based on water contact angle measurements. Anti-fouling performance was evaluated by protein adsorption, cell adhesion, and bacterial adhesion assays, and biocompatibility was assessed using CCK-8 and hemolysis tests. Multiple group comparisons were performed using one-way ANOVA with Tukey′s test, while comparisons between two groups were performed using independent samples t-test.
Results
The MHPBP monomer and three polymers, PMH91, PMH82, and PMH73, were successfully synthesized. The protein adsorption amount on bare PMMA was (4.0 ± 0.5) μg/cm2, which was significantly reduced to (2.6 ± 0.2) μg/cm2 on the PMH82-coated surface (t = 4.8, P = 0.008). The adhesion of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) on bare PMMA was (4.2 ± 0.9) × 105 and (4.3 ± 0.5) × 105 CFU/cm2, respectively, and these values decreased to (2.2 ± 0.2) × 103 and (1.4 ± 0.1) × 103 CFU/cm2 on the PMH82-coated surface (tS. aureus = 7.5, PS. aureus = 0.002; tE. coli = 13, PE. coli<0.001). Cell adhesion assays showed that almost no cells adhered to the PMH82 coating. After 5 days of co-culture, cell viability exceeded 95% in the CCK-8 assay. The hemolysis rate of the coating was only (0.22 ± 0.15) %.
Conclusions
The polymer coating significantly inhibits cell adhesion, bacterial adhesion, and protein adsorption, exhibits good cytocompatibility and an extremely low hemolysis rate, and provides a simple and efficient chairside anti-fouling modification strategy for PMMA denture bases, showing promising prospects for clinical translation.
To construct polyacrylamide hydrogel models with graded Young's moduli and comparable surface roughness, and to evaluate their feasibility for studying stiffness-related changes in the actin cytoskeleton, spreading, and early osteogenic gene expression of mouse bone marrow mesenchymal stem cells (mBMSCs) .
Methods
Three groups of polyacrylamide hydrogels with low, medium, and high stiffness were prepared, characterized for Young's modulus and surface roughness, activated with sulfo-SANPAH, and functionalized with type I collagen. The morphology of F-actin and the relative spreading area of mBMSCs were assessed by fluorescence imaging. Actin polymerization was perturbed with cytochalasin D, followed by 7 days of osteogenic induction and measurement of Alpl and Runx2 expression. Statistical analyses were performed using GraphPad Prism 8. Comparisons among multiple groups were conducted using one-way analysis of variance (ANOVA) or the Kruskal-Wallis test, as appropriate, according to the data distribution and homogeneity of variances. Post hoc pairwise comparisons were performed using Tukey's multiple comparisons test or Dunn's multiple comparisons test, respectively. A two-sided P value of <0.05 was considered statistically significant.
Results
The average Young's moduli of the low-, medium-, and high-stiffness hydrogels were 1.09, 11.37, and 29.24 kPa, respectively, with statistically significant differences (F = 766.60, P<0.001 for all pairwise comparisons), whereas surface roughness did not differ significantly among groups (H = 5.956, P>0.05). Increasing stiffness was associated with more prominent actin bundles and greater cell spreading (H = 14.73, low stiffness group-high stiffness group: P = 0.000 4). Under control conditions, Alpl and Runx2 expression were higher on the high-stiffness group than in the low-stiffness group (FAlpl = 91.54, PAlpl = 0.003 9; FRunx2 = 12.93, PRunx2 = 0.002 5). After cytochalasin D treatment, the differences between the low- and high-stiffness groups were not significant (FAlpl = 91.54, PAlpl = 0.401 9; FRunx2 = 12.93, PRunx2 = 0.887 3) .
Conclusions
The polyacrylamide hydrogel model developed in this study exhibited distinct levels of Young's modulus while maintaining comparable surface roughness. The effects of matrix stiffness on the early osteogenic responses of stem cells may depend, at least in part, on cytoskeletal actin filaments.
Peri-implantitis is a major cause of implant failure, and conventional treatments are limited by incomplete debridement, insufficient drug concentration, and poor bone regeneration capacity. Extracellular vesicles (EVs), as membrane-enclosed structures secreted by cells, show promise in regulating inflammation, promoting tissue regeneration, and enabling targeted therapy. However, natural EVs suffer from insufficient targeting and rapid clearance in vivo. The functional combination of EVs with biomaterials enables local sustained release, enhanced stability, and synergistic promotion of bone regeneration together with scaffold materials. This article reviews the construction strategies for EV-functionalized biomaterials and the research progress on the application of engineered EVs in the prevention and treatment of peri-implantitis, aiming to provide novel engineering strategies and theoretical foundations for the precise management of peri-implantitis.
Vat photopolymerization (VPP) is a crucial 3D printing technology for fabricating ceramic dentures. However, nonlinear dimensional deviations and warpage distortion during the fabrication process severely restrict their clinical adaptability. This review aims to systematically summarize the latest research progress in digital morphological design and deformation compensation strategies for VPP 3D-printed ceramic dentures, providing theoretical guidance for high-precision manufacturing. In geometric morphology design, the applications of artificial intelligence (AI) algorithms, such as 3D convolutional neural networks, generative adversarial networks, and PointNet methods, were analyzed. Regarding deformation compensation, linear compensation algorithms like anisotropic scaling factors and slice contour offsets were examined. Crucially, nonlinear pre-deformation compensation strategies, including finite element thermodynamic simulations, AI-based nonlinear shrinkage prediction models, and conformal support structures, were discussed in detail. Results indicated that AI algorithms are driving the transition of denture design from experience-based paradigms to data-driven and high-fidelity intelligent models. While linear compensation algorithms effectively correct macroscopic dimensional deviations, they struggle with non-uniform distortions. Conversely, finite element simulations and AI nonlinear shrinkage prediction models can effectively suppress complex nonlinear deformations, significantly improving the final clinical adaptation accuracy of ceramic dentures. Ultimately, digital morphological design and nonlinear deformation compensation technologies are fundamental to improving the accuracy of VPP ceramic dentures. Future research should further explore denture design under dynamic biomechanical coupling and promote the clinical application of AI pre-deformation algorithms for complex, personalized dentures.
To systematically elucidate the molecular mechanism by which Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) modulates carnitine palmitoyltransferase 1A (CPT1A) to influence metabolic reprogramming and apoptosis in foam cells, and to explore the potential link between periodontal pathogen infection and the progression of atherosclerosis.
Methods
Transcriptome sequencing was employed to analyze the whole-genome expression profiles of foam cells stimulated by P. gingivalis-LPS. Differentially expressed genes (DEGs) were screened, and functional enrichment analysis was conducted using bioinformatics methods. Further validation of the core regulatory role of CPT1A in lipid metabolism and apoptosis was performed through gene overexpression and apoptosis assays.
Results
Transcriptomic analysis identified 427 DEGs (318 upregulated and 109 downregulated) under the thresholds of |log2FC|>1 and FDR<0.05. GO and KEGG enrichment analyses based on these DEGs indicated significant enrichment in lipid- and sterol-related biological processes, as well as the PPAR signaling pathway, fatty acid metabolism, and steroid biosynthesis. GSEA results showed that cholesterol/sterol biosynthesis-related pathways were negatively enriched, whereas fatty acid transport and adaptive lipid metabolic processes were positively enriched. In addition, apoptosis-related pathways, including the p53 pathway, were also positively enriched. Among these, CPT1A expression was markedly elevated and confirmed as a key regulator. Functional studies demonstrated that CPT1A overexpression enhanced cell viability and suppressed apoptosis (P<0.05) .
Conclusions
CPT1A may mediate the promotion of atherosclerotic foam cell pathogenesis by periodontal pathogen infection via coordinating lipid metabolic reprogramming and apoptosis resistance.