The Effect of COVID-19 Infection on Orofacial Pain: A Cross-sectional Study.

BACKGROUND: COVID-19 infection shows variant symptoms apart from respiratory symptoms, including the orofacial pain. We aim to research the morbidity, characteristics and potential risk factors of orofacial pain associated with COVID-19 pandemic in China from December 2022 to early 2023. METHODS: A cross-sectional survey was conducted in Fujian Province, China. The demographic and characteristic data of the subjects were collected and analysed. RESULTS: A total of 1526 subjects responded to the survey. The morbidity of orofacial pain increased significantly before and after COVID-19 infection. (42.26% vs. 46.52%, P < .001) A total of 217 (14.22%) subjects with orofacial pain before COVID-19 infection reported the phenomenon of "COVID-19 infection with orofacial pain" (CIOP). Univariate and multivariate logistic regression showed that male (OR = 1.761, P < .001) and other symptoms of COVID-19 (OR = 1.494, P < .001) may be the risk factors for the aggravation of CIOP, while the time of first infection (OR = 0.580, P = .004) and preference for drinking tea or coffee (OR = 0.610, P = .003) may be the protective factors for the aggravation of CIOP. While, the subjects who did not concern about the spread of COVID-19 in oral treatment (OR = 0.639, P = .001), female (OR = 0.749, P = .03), education level (OR = 1.687, P < .001) and income level (OR = 1.796, P < .001), higher PSS-10 score (OR = 1.076, P < .001), and more drugs taken for infection (OR = 1.330, P < .001) were more willing to seek medical treatment. CONCLUSION: The morbidity of orofacial pain appears to have increased significantly due to the COVID-19 epidemic; a number of factors can influence the CIOP including gender, infection period, and beverage preference' psychological factors, gender, education and income level can also influence the intent to seek a dentist.

Nanoporous, Ultrastiff, and Transparent Plastic-like Polymer Hydrogels Enabled by Hydrogen Bonding-Induced Self-Assembly.

Most natural supporting tissues possess both exceptional mechanical strength, a significant amount of water, and the anisotropic structure, as well as nanoscale assembly. These properties are essential for biological processes, but have been challenging to emulate in synthetic materials. In an effort to achieve simultaneous improvement of these trade-off features, a hydrogen bonding-induced self-assembly strategy was introduced to create nanoporous plastic-like polymer hydrogels. Multiple hydrogen bonding-mediated networks and nanoporous orientation structures endow transparent hydrogels with remarkable mechanical robustness. They exhibit Young's modulus of up to 223.7 MPa and a breaking strength of up to 10.3 MPa, which are superior to those of most common polymer hydrogels. The uniform porous nanostructures of hydrogen-bonded hydrogels contribute to a significantly larger specific surface area compared to conventional hydrogels. This allows for the retention of high mechanical properties in environments with a high water content of 70 wt %. A rubbery stage is observed during the heating process, which can reverse and reshape the manufacture of objects with various desired 2D or 3D shapes using techniques such as origami and kirigami. Finally, as a proof-of-concept, the outstanding mechanical properties of poly(MAA-co-AA-co-NVCL) hydrogel, combined with its high water content, make it suitable for applications such as smart temperature monitors, multilevel information anticounterfeiting, and artificial muscles.

Lactate promotes bone healing by regulating the osteogenesis of bone marrow mesenchymal stem cells through activating Olfr1440.

Bone malunion or nonunion leads to functional and esthetic problems and is a major healthcare burden. Activation of bone marrow mesenchymal stem cells (BMSCs) and subsequent induction of osteogenic differentiation by local metabolites are crucial steps for bone healing, which has not yet been completely investigated. Here, we found that lactate levels are rapidly increased at the local injury site during the early phase of bone defect healing, which facilitates the healing process by enhancing BMSCs regenerative capacity. Mechanistically, lactate serves as a ligand for the Olfr1440 olfactory receptor, to trigger an intracellular calcium influx that in turn activates osteogenic phenotype transition of BMSCs. Conversely, ablation of Olfr1440 delays skeletal repair and remodelling, as evidenced by thinner cortical bone and less woven bone formation in vivo. Administration of lactate in the defect area enhanced bone regeneration. These findings thus revealed the key roles of lactate in the osteogenic differentiation of BMSCs, which deepened our understanding of the bone healing process, as well as provided cues for a potential therapeutic option that might greatly improve bone defect treatment.

Adaptive truncation of the S gene in IBV during chicken embryo passaging plays a crucial role in its attenuation.

Like all coronaviruses, infectious bronchitis virus, the causative agent of infectious bronchitis in chickens, exhibits a high mutation rate. Adaptive mutations that arise during the production of live attenuated vaccines against IBV often decrease virulence. The specific impact of these mutations on viral pathogenicity, however, has not been fully elucidated. In this study, we identified a mutation at the 3' end of the S gene in an IBV strain that was serially passaged in chicken embryos, and showed that this mutation resulted in a 9-aa truncation of the cytoplasmic tail (CT) of the S protein. This phenomenon of CT truncation has previously been observed in the production of attenuated vaccines against other coronaviruses such as the porcine epidemic diarrhea virus. We next discovered that the 9-aa truncation in the S protein CT resulted in the loss of the endoplasmic-reticulum-retention signal (KKSV). Rescue experiments with recombinant viruses confirmed that the deletion of the KKSV motif impaired the localization of the S protein to the endoplasmic-reticulum-Golgi intermediate compartment (ERGIC) and increased its expression on the cell surface. This significantly reduced the incorporation of the S protein into viral particles, impaired early subgenomic RNA and protein synthesis, and ultimately reduced viral invasion efficiency in CEK cells. In vivo experiments in chickens confirmed the reduced pathogenicity of the mutant IBV strains. Additionally, we showed that the adaptive mutation altered the TRS-B of ORF3 and impacted the transcriptional regulation of this gene. Our findings underscore the significance of this adaptive mutation in the attenuation of IBV infection and provide a novel strategy for the development of live attenuated IBV vaccines.

Cadmium contamination decreased bacterial network complexity and stability in coastal reclamation areas.

Cadmium(Cd) contamination can exert significantly adverse effects on soil microbiota in reclaimed areas, however, its effects on bacterial network structure are still limitedly understood. Here we collected soil samples from typical reclaimed wetlands (RW) and ditch wetlands (DW) in coastal reclamation areas and examined the effects of Cd contamination on the bacterial network complexity and stability. The results showed that the bacterial networks were destabilized by the Cd contamination, while bacteria in DW soils showed robust invulnerability characterized by higher node constancy and compositional stability compared with RW soils. Soil bacteria resisted Cd stress by forming a network with intensive connections in the module but sparser connections among the modules. Especially, network modularity was higher in DW soils than in RW soils, but made it more vulnerable to nodes removal. In addition, Cd contamination promoted bacterial positive cohesion but decreased negative cohesion in RW soils. Flavobacteriaceae, Xanthomonadaceae, and Alcaligenaceae were identified as core phylotypes, which played pivotal roles in regulating interspecies interactions due to higher contributions to cohesion and significant correlations with soil nutrients. The findings of this work indicate the changes of bacterial network structure and the indispensable role of core phylotypes in regulating interactions and maintaining network sustainability under Cd contamination.

Discovery of a novel DYRK1A inhibitor with neuroprotective activity by virtual screening and in vitro biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is implicated in accumulation of amyloid ß-protein (Aß) and phosphorylation of Tau proteins, and thus represents an important therapeutic target for neurodegenerative diseases. Though many DYRK1A inhibitors have been discovered, there is still no marketed drug targeting DYRK1A. This is partly due to the lack of effective and safe chemotypes. Therefore, it is still necessary to identify new classes of DYRK1A inhibitors. By performing virtual screening with the workflow mainly composed of pharmacophore modeling and molecular docking as well as the following DYRK1A inhibition assay, we identified compound L9, ((Z)-1-(((5-phenyl-1H-pyrazol-4-yl)methylene)-amino)-1H-tetrazol-5-amine), as a moderately active DYRK1A inhibitor (IC50: 1.67 µM). This compound was structurally different from the known DYRK1A inhibitors, showed a unique binding mode to DYRK1A. Furthermore, compound L9 showed neuroprotective activity against okadaic acid (OA)-induced injury in the human neuroblastoma cell line SH-SY5Y by regulating the expression of Aß and phosphorylation of Tau protein. This compound was neither toxic to the SH-SY5Y cells nor to the human normal liver cell line HL-7702 (IC50: >100 µM). In conclusion, we have identified a novel DYRK1A inhibitor with neuroprotective activity through virtual screening and in vitro biological evaluation, which holds the promise for further study.

Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

HtrA3 paves the way for MSC migration and promotes osteogenesis.

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin ß1 expression. Subsequently, integrin ß1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

Discovery of a novel chemotype as DYRK1A inhibitors against Alzheimer's disease: Computational modeling and biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) plays an essential role in Tau and Aß pathology closely related to Alzheimer's disease (AD). Accumulative evidence has demonstrated DYRK1A inhibition is able to reduce the pathological features of AD. Nevertheless, there is no approved DYRK1A inhibitor for clinical use as anti-AD therapy. This is somewhat due to the lack of effective and safe chemotypes of DYRK1A inhibitors. To address this issue, we carried out in silico screening, in vitro assays and in vivo efficacy evaluation with the aim to discover a new class of DYRK1A inhibitors for potential treatment of AD. By in silico screening, we selected and purchased 16 potential DYRK1A inhibitors from the Specs chemical library. Among them, compound Q17 (Specs ID: AO-476/40829177) potently inhibited DYRK1A. The hydrogen bonds between compound Q17 and two amino acid residues named GLU239 and LYS188, were uncovered by molecular docking and molecular dynamics simulation. The cell-based assays showed that compound Q17 could protect the SH-SY5Y human neuroblastoma cell line from okadaic acid (OA)-induced injury by targeting DYRK1A. More importantly, compound Q17 significantly improved cognitive dysfunction of 3 × Tg-AD mice, ameliorated pathological changes, and attenuated Tau hyperphosphorylation as well as Aß deposition. In summary, our computational modeling strategy is effective to identify novel chemotypes of DYRK1A inhibitors with great potential to treat AD, and the identified compound Q17 in this study is worthy of further study.

An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy.

Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in the TME. To leverage TBYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding TBYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing TBYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration.

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Cafestol inhibits colon cancer cell proliferation and tumor growth in xenograft mice by activating LKB1/AMPK/ULK1-dependent autophagy.

Chemotherapy failure in colorectal cancer patients is the major cause of recurrence and poor prognosis. As a result, there is an urgent need to develop drugs that have a good chemotherapy effect while also being extremely safe. In this study, we found cafestol inhibited colon cancer growth and HCT116 proliferation in vivo and in vitro, and improved the composition of intestinal flora. Further metabolomic data showed that autophagy and AMPK pathways were involved in the process of cafestol's anti-colon cancer effects. The functional validation studies revealed that cafestol increased autophagy vesicles and LC3B-II levels. The autophagic flux induced by cafestol was prevented by using BafA1. The autophagy inhibitor 3-MA blocked the cafestol-induced increase in LC3B-II and cell proliferation inhibition. Then we found that cafestol induced the increased expressions of LKB1, AMPK, ULK1, p-LKB1, p-AMPK, and p-ULK1 proteins in vivo and in vitro. Using the siRNA targeted to the Lkb1 gene, the levels of AMPK, ULK1, and LC3B-II were suppressed under cafestol treatment. These results indicated that the effect of cafestol is through regulating LKB1/AMPK/ULK1 pathway-mediated autophagic death. Finally, a correlation matrix of the microbiome and autophagy-related proteins was conducted. We found that cafestol-induced autophagic protein expression was positively correlated with the beneficial intestinal bacteria (Muribaculaceae, Bacteroides, Prevotellacece, and Alloprevotella) and negatively correlated with the hazardous bacteria. Conclusions: This study found that cafestol inhibited colon cancer in vitro and in vivo by the mechanism that may be related to LKB1/AMPK/ULK1 pathway-mediated autophagic cell death and improved intestinal microenvironment.

Multi-scale and multi-view network for lung tumor segmentation.

Lung tumor segmentation in medical imaging is a critical step in the diagnosis and treatment planning for lung cancer. Accurate segmentation, however, is challenging due to the variability in tumor size, shape, and contrast against surrounding tissues. In this work, we present MSMV-Net, a novel deep learning architecture that integrates multi-scale multi-view (MSMV) learning modules and multi-scale uncertainty-based deep supervision (MUDS) for enhanced segmentation of lung tumors in computed tomography images. MSMV-Net capitalizes on the strengths of multi-view analysis and multi-scale feature extraction to address the limitations posed by small 3D lung tumors. The results indicate that MSMV-Net achieves state-of-the-art performance in lung tumor segmentation, recording a global Dice score of 55.60% on the LUNA dataset and 59.94% on the MSD dataset. Ablation studies conducted on the MSD dataset further validate that our method enhances segmentation accuracy.

Life's Essential 8, Life's Simple 7 and the odds of hyperuricaemia: results from the China Multi-Ethnic Cohort Study.

Objective: Life's Essential 8 (LE8) is a new comprehensive metric based on Life's Simple 7 (LS7). Few studies have investigated the association between LE8 and the odds of hyperuricaemia (HUA). This study examined the association between LE8, LS7 with odds of HUA. Methods: We cross-sectionally analysed data from the China Multi-Ethnic Cohort (CMEC) study. LE8 and LS7 were categorized as low, moderate and high. The CMEC provided an ideal and unique opportunity to characterize the association between LE8, LS7 and the odds of HUA. Results: Of the 89 823 participants, 14 562 (16.2%) had HUA. A high level of LE8 was associated with lower odds of HUA after full adjustment. The adjusted odds ratios (ORs) were 1 (reference), 0.70 (95% CI 0.67, 0.73) and 0.45 (0.42, 0.48) across low, moderate and high LE8 groups, respectively (Ptrend < 0.001). Similar results were observed in LS7 and HUA. The adjusted ORs were 1 (reference), 0.68 (95% CI 0.65, 0.71) and 0.46 (95% CI 0.43, 0.49) across low, moderate and high LS7 groups, respectively (Ptrend < 0.001). There were significant interactions between LE8 and age, gender, ethnicity and drinking habits on HUA. Receiver operating characteristics analysis showed that the area under the curve for LE8 and LS7 were similar (0.638 and 0.635, respectively). Conclusion: This study indicated a clearly inverse gradient association between the cardiovascular health metrics LE8 and LS7 and the odds of HUA.

CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

[Bionic design, preparation and clinical translation of oral hard tissue restorative materials].

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

Manipulating the Generation of Photonic Moiré Lattices Using Plasmonic Metasurfaces.

The generation of moiré lattices by superimposing two identical sublattices at a specific twist angle has garnered significant attention owing to its potential applications, ranging from two-dimensional materials to manipulating light propagation. While macroscale moiré lattices have been widely studied, further developments in manipulating moiré lattices at the subwavelength scale would be crucial for miniaturizing and integrating platforms. Here, we propose a plasmonic metasurface design consisting of rotated nanoslits arranged within N + N' round apertures for generating focused moiré lattices. By introducing a spin-dependent geometric phase through the rotated nanoslits, an overall lens and spiral phase can be achieved, allowing each individual set of round apertures to generate a periodic lattice in the focal plane. Superimposing two sets of N and N' apertures at specific twist angles and varying phase differences allows for the superposition of two sublattices with different periods, leading to the formation of diverse moiré patterns. Our simulations and theoretical results demonstrate the feasibility of our proposed metasurface design. Due to their compactness and tunability, the utilization of metasurfaces in creating nanoscale photonic moiré lattices is anticipated to find extensive applications in integrated and on-chip optical systems.

Programmable Electro-Assembly of Collagen: Constructing Porous Janus Films with Customized Dual Signals for Immunomodulation and Tissue Regeneration in Periodontitis Treatment.

Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability- in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti-inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro-assembly under pre-programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS-containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS-containing porous layer delivers dual bio-signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine.

Lithiated porous silicon nanowires stimulate periodontal regeneration.

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/ß-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/ß-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.