Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation.

BACKGROUND: Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. METHODS: FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. RESULTS: The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. CONCLUSION: In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials.

Unraveling the multi-pollutant removal using M-MoWTi (M = Fe, Mn, Cr) catalyst: experiment and mechanistic study of competition for active sites.

Multi-pollutant removal (MPR) of NO and VOCs simultaneously is efficient of flue gas treatment in coal-fired power plants. But reducing the competition for active sites between NH3, NO, C6H6, and C7H8 remains challenging. Herein, Cr, Mn, and Fe were respectively doped to MoWTi catalyst via wet impregnation. The Fe3+ + Mo5+ ↔ Fe2+ + Mo6+ redox cycle led to an increased proportion of low valence ions (Mo5+ and W5+) and facilitated the creation of active oxygen vacancies with several active sites. It also possessed plentiful mild to strong acid sites with ideal ratio. These factors enhanced catalytic activity of Fe-MoWTi. Remarkable MPR efficiencies of NO, C6H6, and C7H8 were achieved under industrial SCR condition, characterized by low oxygen but high SO2 levels at 340 °C, with removal rates reaching 89.85%, 97.57%, and 86.30% respectively. Theory calculations further revealed that Fe-MoWTi favor NH3 and O2 adsorptions. NO elimination was found to follow both Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) processes, supported by in situ DRIFTS analysis. The reactions involving NO/NO2/nitrite/nitrate occurred with NH3(ads)/ NH4+(ads)/NH2 (ads). C6H6 and C7H8 underwent gradual oxidation, formatting alcohols, aldehydes, acids, and maleic acids, before eventually being mineralized to gaseous CO2 and H2O. Findings hold significant potential for application, providing guidance for the development of catalysts with improved resistance against SO2 poisoning and enhanced MPR capabilities.

Transcriptome analysis of Chinese mitten crabs (Eriocheir sinensis) gills in response to ammonia stress.

The Chinese mitten crab (Eriocheir sinensis) is an important commercial species in China. E. sinensis is typically farmed in rice-crab symbiosis, as an important ecological farming model. However, E. sinensis is often exposed to a high ammonia environment due to the application of nitrogen fertilizers essential for rice growth. We investigated the molecular mechanisms in the gills of E. sinensis exposed to high ammonia at transcriptional and histological levels. We randomly assigned E. sinensis to two groups (control group, CG; ammonia stress group, AG), and gill samples were excised from the CG and AG groups for histopathological and transcriptome analyses. The histopathological evaluation revealed that ammonia stress damaged the gills of E. sinensis. The transcriptome analysis showed that some essential genes, including Xanthine dehydrogenase (XDH), Ubiquitin C-terminal hydrolase-L3 (UCHL3), O-linked N-acetylglucosamine transferase (OGT), Cathepsin B (CTSB), and Ubiquitin-conjugating enzyme E2 W (UBE2W) changed significantly during ammonia exposure. These genes are related to ammonia detoxification, the immune response, and apoptosis. This study demonstrated the molecular response mechanism of E. sinensis gills to ammonia stress at the transcriptional and histological levels. This study provides insight for further study on the molecular mechanism of ammonia stress in crustaceans and supplies technical support for rice crab symbiosis.

Copper/Nickel/Cobalt modified molybdenum-tungsten-titanium dioxide-based catalysts for multi-pollution control of nitrogen oxide, benzene, and toluene: Enhanced redox capacity and mechanism study.

Previous studies have indicated the potential of monometallic-modified TiO2 catalysts in controlling nitrogen oxide (NOx) and volatile organic compounds (VOCs) in coal-fired flue gas. Unfortunately, increasing selective catalytic reduction (SCR) activity under complicated coal-fired flue gas status is tricky. In this study, modified Co-MoWTiO2 catalysts with multiple active sites were synthesized using the wet impregnation method, which exhibited excellent multi-pollution control ability of NO, benzene and toluene under low oxygen and high SO2 concentrations. The modification of Mo and Co achieved high dispersion and electron transfer. The interaction between W5+/W6+ and Co2+/Co3+ promoted gas-phase O2 adsorption on the catalyst surface, forming of reactive oxygen species (Oα). Density functional theory (DFT) calculations informed that the doping of Co effectively enhanced the NH3 and O2 adsorption capacity of the catalyst, and Co possessed the maximum adsorption energy for NH3 and O2. Possible pathways of multi-pollution control of NO, C6H6, and C7H8 were speculated. NH3/NH4+ on the Lewis/Bronsted acid site is reacted with intermediates of NO (e.g., NO2, nitrite, nitrate) via the Langmuir-Hinshelwood and Eley-Rideal mechanism. The introduction of NO and NH3 did not disrupt the oxidation pathways of benzene and toluene. Following the Mars-van Krevelen mechanism, C6H6 and C7H8 were progressively mineralized by Oα into CO2 and H2O.

Surgical performance of dental students using computer-assisted dynamic navigation and freehand approaches.

INTRODUCTION: Nowadays, the training of implant placement has shifted from once entirely instructor-student teaching to the increasing use of computer-assisted simulation. Based on computerized virtual planning, dynamic navigation has been used for implant placement with higher accuracy than the traditional freehand protocol. However, whether dynamic navigation benefits to the training of dental students in implant placement remains controversial. This study aimed to compare the surgical performance of dental students in implant placement using computer-assisted dynamic navigation and freehand approaches. MATERIALS AND METHODS: A total of 20 dental students (6 males, 14 females, age: 25.6 ± 0.5 years) were enrolled in this study. With the traditional freehand approach (training 1) as the control protocol, computer-assisted dynamic navigation (training 2) was used in the training of dental students in implant placement. For each training, both the operating time (OT) of students and placement accuracy represented by the linear (at the implant platform, Dpl, and apex, Dap) and angular (Dan) deviations between the virtually planned and placed implants were recorded. Statistical comparisons were made between the two training protocols as well as male and female surgeons. RESULTS: OT2 was around twice of OT1 (p < .0001), whereas Dan1 was almost three times of Dan2 (p < .0001). Dap1 and Dpl1 were significantly higher than Dap2 (p = .014) and Dpl2 (p = .033) respectively. Besides, male students showed statistically higher Dpl1 (p = .033) and Dan1 (p = .002) than females. No significant difference was found between male and female students in OT1, OT2, Dpl2, Dap1, Dap2 and Dan2. CONCLUSIONS: Within the limitations of this study, the use of computer-assisted dynamic navigation in the preclinical training could improve the surgical performance of the dental students in implant placement. The combination of dynamic navigation with the traditional preclinical surgical training may benefit to dental students and could be applied in dental education.

The influence of guide stabilizers and their application sequences on trueness and precision of surgical guides in free end situations: An in vitro analysis.

OBJECTIVES: To evaluate the impact of guide stabilizers and their application sequences on implant placement accuracy of guided implant surgery in multiple teeth loss at free end. MATERIALS AND METHODS: In this study, 96 implants were placed in the regions of #34, #36, and #37 of 32 identical mandibular models. The influence of using guide stabilizers or not (group A and group B) and various guide stabilizers application sequences (group B: #34 → #36 → #37; group C: #36 → #34 → #37; group D: #37 → #34 → #36) on implant placement trueness and precision was investigated. Data were analyzed using T-tests and one-way ANOVA. RESULTS: Group B showed significant benefits in enhancing implant placement precision. Compared to group A, it resulted in reducing 3D-deviation at crest and 2D deviation in vestibular-oral direction at both crest and apex. Furthermore, group D demonstrated greater improvement in global implant placement precision by reducing 2D deviation in mesial-distal direction at both crest and apex. Among the three different stabilizer application sequences, group D exhibited the highest level of implant placement precision. CONCLUSIONS: In cases of missing teeth at distal free end, the use of guide stabilizers and their application sequences does not have a significant impact on implant placement trueness. However, they do improve implant placement precision compared to methods that do not utilize guide stabilizers. Specifically, applying a guide stabilizer first at the furthest implant site to change teeth loss classification from free end to edentulous space with posterior support is the most reliable sequence.

Prediction of primary stability via the force feedback of an autonomous dental implant robot.

STATEMENT OF PROBLEM: While the high osteotomy and implant placement accuracy via robotic implant surgery has been verified, whether the force feedback in the osteotomy process can be used to determine appropriate primary implant stability remains unknown. PURPOSE: The purpose of this in vitro study was to explore the relationship between the force feedback and the primary stability of implants placed by using an autonomous dental implant robot. MATERIAL AND METHODS: Five groups (n=7) of wooden and polyurethane foam blocks were used to execute an implant surgery by using an autonomous implant robot. Tapered bone-level titanium dental implant replicas were placed in the blocks. The Young modulus, the maximal vertical and lateral drilling resistances, the position accuracy, and the insertion torque of implants were recorded. Simple linear regression, principal component analysis, and multiple linear regression were used. The osteotomy strategy for the implant site was adjusted according to the maximal vertical resistance of the pilot drill to achieve appropriate insertion torque. The correlation, Gompertz growth curve fitting of the insertion torque, and Young modulus were determined. The effect of the drilling resistances on the insertion torque was analyzed using 2-way ANOVA, simple linear regression, and the principal component analysis. RESULTS: The vertical resistance of the Ø2.2-mm pilot drill, the Ø3.5-mm twist drill, and the Ø4.1-mm profile drill had a strong simple linear correlation with the insertion torque of the implants, and the lateral resistance had a moderate linear correlation with the insertion torque. The contributions of these 6 variables to the implant torque, among which the vertical resistance of the twist drill and the pilot drill ranked first and second, were comparable. Adjustments to the strategy of site preparation according to the vertical resistance of the pilot drill achieved appropriate insertion torque (P<.001). CONCLUSIONS: The force feedback of the autonomous dental implant robot was significantly correlated with the insertion torque of implants, which may fit an interpretable mathematical model, allowing dental implants to be placed with predictable primary stability.

Balance between the CMC/ACP Nanocomplex and Blood Assimilation Orchestrates Immunomodulation of the Biomineralized Collagen Matrix.

Calcium phosphate-based biomineralized biomaterials have broad application prospects. However, the immune response and foreign body reactions elicited by biomineralized materials have drawn substantial attention recently, contrary to the immune microenvironment optimization concept. Therefore, it is important to clarify the immunomodulation properties of biomineralized materials. Herein, we prepared the biomineralized collagen matrix (BCM) and screened the key immunomodulation factor carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP) nanocomplex. The immunomodulation effect of the BCM was investigated in vitro and in vivo. The BCM triggered evident inflammatory responses and cascade foreign body reactions by releasing the CMC/ACP nanocomplex, which activated the potential TLR4-MAPK/NF-κB pathway, compromising the collagen matrix biocompatibility. By contrast, blocking the CMC/ACP nanocomplex release via the blood assimilation process of the BCM mitigated the inflammation and foreign body reactions, enhancing biocompatibility. Hence, the immunomodulation of the BCM was orchestrated by the balance between the CMC/ACP nanocomplex and the blood assimilation process. Controlling the release of the CMC/ACP nanocomplex to accord the biological effects of ACP with the temporal regenerative demands is key to developing advanced biomineralized materials.

A Layered Aluminophosphate [C17H21N2]3[Al3(PO4)4]·5H2O with Fluorescent Property Derived from Carbazolyl-Modified Template.

Designing and innovating organic structure-directing agents is the key to synthesizing novel molecular sieve structures. Herein, we design a novel carbazolyl-modified template and further synthesize a two-dimensional layered aluminophosphate with [C17H21N2]3[Al3(PO4)4]·5H2O (denoted as ZHKU-2). ZHKU-2 is composed of AA-stacked [Al3P4O16]3- layers constructed from alternating AlO4 and PO3(=O) tetrahedrons to form a 4.6.8 network featured by capped six-ring secondary building units. Carbazolyl-templated ZHKU-2 exhibits strong purple fluorescence with a high quantum yield of 25.98%. This work expands aluminophosphate materials of the [Al3P4O16]3- family and provides a view for synthesizing new molecular sieves by exploring the organic luminescence structure-directing agents.

Regulating Blood Clot Fibrin Films to Manipulate Biomaterial-Mediated Foreign Body Responses.

The clinical efficacy of implanted biomaterials is often compromised by host immune recognition and subsequent foreign body responses (FBRs). During the implantation, biomaterials inevitably come into direct contact with the blood, absorbing blood protein and forming blood clot. Many studies have been carried out to regulate protein adsorption, thus manipulating FBR. However, the role of clot surface fibrin films formed by clotting shrinkage in host reactions and FBR is often ignored. Because of the principle of fibrin film formation being relevant to fibrinogen or clotting factor absorption, it is feasible to manipulate the fibrin film formation via tuning the absorption of fibrinogen and clotting factor. As biological hydroxyapatite reserved bone architecture and microporous structure, the smaller particle size may expose more microporous structures and adsorb more fibrinogen or clotting factor. Therefore, we set up 3 sizes (small, <0.2 mm; medium, 1 to 2 mm; large, 3 to 4 mm) of biological hydroxyapatite (porcine bone-derived hydroxyapatite) with different microporous structures to investigate the absorption of blood protein, the formation of clot surface fibrin films, and the subsequent FBR. We found that small group adsorbed more clotting factors because of more microporous structures and formed the thinnest and sparsest fibrin films. These thinnest and sparsest fibrin films increased inflammation and profibrosis of macrophages through a potential signaling pathway of cell adhesion-cytoskeleton-autophagy, leading to the stronger FBR. Large group adsorbed lesser clotting factors, forming the thickest and densest fibrin films, easing inflammation and profibrosis of macrophages, and finally mitigating FBR. Thus, this study deepens the understanding of the role of fibrin films in host recognition and FBR and demonstrates the feasibility of a strategy to regulate FBR by modulating fibrin films via tuning the absorption of blood proteins.

Optimized osteogenesis of porcine bone-derived xenograft through surface coating of magnesium-doped nanohydroxyapatite.

As one of the key factors influencing the outcome of guided bone regeneration, the currently used xenografts possess insufficient capability in osteogenesis. With the aim of improving the osteogenic performance of xenografts, porcine bone-derived hydroxyapatite (PHA) was prepared and subsequently coated by magnesium-doped nano hydroxyapatite (nMgHA, 10%, 20%, and 30% of Mg/Ca + Mg) through a straightforward and cost-efficient approach. The physiochemical and biological properties of nMgHA/PHAs were examinedin vitroandin vivo. The inherent three-dimensional (3D) porous framework with the average pore size of 300 µm was well preserved in nMgHA/PHAs. Meanwhile, excess magnesium released from the so-called 'surface pool' of PHA was verified. In contrast, slower release of magnesium at lower concentrations was detected for nMgHA/PHAs. Significantly more newly-formed bone and microvessels were observed in 20%nMgHA/PHA than the other specimens. With the limitations of the present study, it could be concluded that PHA coated by 20%nMgHA may have the optimized osteogenic performance due to the elimination of the excess magnesium from the 'surface pool', the preservation of the inherent 3D porous framework with the favorable pore size, and the release of magnesium at an appropriate concentration that possessed osteoimmunomodulatory effects on macrophages.

2-DG Regulates Immune Imbalance on the Titanium Surface after Debridement.

Peri-implantitis requires clinical treatments comprised of mechanical and chemical debridement to remove bacterial biofilms. Bone regeneration on the titanium surface after debridement has been a topical issue of peri-implantitis treatments. Increasing evidence has revealed that the immune microenvironment plays a key role in regulating the bone regeneration process. However, it remains unclear what kind of immune microenvironment the titanium surface induces after debridement. In the study, model titanium surface after debridement was prepared via biofilm induction and mechanical and chemical debridement in vitro. Then, the macrophages and naïve CD4+ T lymphocytes were cultured on the titanium surface after debridement for immune microenvironment evaluation, with the original titanium surface as the control. Next, to regulate the immune microenvironment, 2-DG, a glycolysis inhibitor, was further incorporated to regulate macrophages and CD4+ T lymphocytes at the same time. Surface characterization results showed that the bacterial biofilms were completely removed, while the micro-morphology of titanium surface altered after debridement, and the element composition did not change. Compared with the original titanium disc, titanium surface after debridement can lead to the inflammatory differentiation of macrophages and CD4+ T lymphocytes. The percentage of M1 and Th17 inflammatory cells and the expression of their inflammatory factor genes are upregulated. However, 0.3 mmol of 2-DG can significantly reduce the inflammatory differentiation of both macrophages and CD4+ T lymphocytes and inhibit their expression of inflammatory genes. In conclusion, although bacterial biofilms were removed from titanium surface after debridement, the surface topography changes could still induce immune imbalance and form an inflammatory immune microenvironment. However, this inflammatory immune microenvironment can be effectively reversed by 2-DG in vitro, thus creating an immune microenvironment conducive to osteogenesis, which might provide a new perspective for future therapy of peri-implantitis.

Clinical and radiographic results of crestal vs. subcrestal placement of implants in posterior areas: A split-mouth randomized controlled clinical trial.

OBJECTIVE: The objective of this study was to evaluate the peri-implant soft tissue and marginal bone loss (MBL) around implants with platform-switching and internal conical connection placed at crestal and subcrestal levels in posterior areas. MATERIALS AND METHODS: Nineteen partially edentulous patients with at least two adjacent missing teeth in posterior areas unilaterally or bilaterally were included. Forty-two implants were placed randomly at the crestal or subcrestal (1 mm) level in a split-mouth design. Implant-supported fixed dental prostheses with screw retention were delivered after 4 months of healing. Clinical and radiological measurements were performed at implant placement (T0), restoration delivery (T1), and 1-year follow-up after loading (T2). MBL was calculated as the change in distance from the implant-abutment interface to the first radiographically visible bone-implant contact. A repeated-measures mixed ANOVA followed by a paired Student's t-test with the Bonferroni correction was used for statistical analysis. p < 0.05 was considered statistically significant. RESULTS: Eighteen patients with thirty-eight implants completed the study at T2. The MBL was lower in the subcrestal group than in the crestal group (0.04 ± 0.08 vs. 0.17 ± 0.17 mm, p = 0.004). The peri-implant probing depth (PD) was 2.31 ± 0.48 mm in the subcrestal group and 1.92 ± 0.43 mm in the crestal group; this difference was statistically significant (p = 0.002). Intragroup comparison showed no significant differences in MBL, or PD around the crestal group and subcrestal group from T1 to T2. CONCLUSION: After 1 year of functional loading, subcrestal placement of implants with platform-switching and internal conical connection showed lower MBL and was associated with greater PD and peri-implant soft tissue height than implants placed at the crestal level.

Tailoring the multiscale mechanics of tunable decellularized extracellular matrix (dECM) for wound healing through immunomodulation.

With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.

Transcriptome analysis of human peri-implant soft tissue and periodontal gingiva: a paired design study.

OBJECTIVES: Limited information is available about the biological characterization of peri-implant soft tissue at the transcriptional level. The aim of this study was to investigate the effect of dental implant on the soft tissue in vivo by using paired samples and compare the differences between peri-implant soft tissue and periodontal gingiva at the transcriptional level. METHODS: Paired peri-implant soft tissue and periodontal gingiva tissue from 6 patients were obtained, and the pooled RNAs were analyzed by deep sequencing. Venn diagram was used to further screen out differentially expressed genes in every pair of samples. Annotation and enrichment analysis was performed. Further verification was done by quantitative real-time PCR. RESULTS: Totally 3549 differentially expressed genes (DEGs) were found between peri-implant and periodontal groups. The Venn diagram further identified 185 DEGs in every pair of samples, of which the enrichment analysis identified significant enrichment for cellular component was associated with external side of plasma membrane, for molecular function was protein binding, for biological process was immune system process, and for KEGG pathway was cytokine-cytokine receptor interaction. Among the DEGs, CST1, SPP1, AQP9, and SFRP2 were verified to be upregulated in peri-implant soft tissue. CONCLUSIONS: Peri-implant soft tissue showed altered expressions of several genes related to the cell-ECM interaction compared to periodontal gingiva. CLINICAL RELEVANCE: Compared to periodontal gingiva, altered cell-ECM interactions in peri-implant may contribute to the susceptibility of peri-implant diseases. At the transcriptional level, periodontal gingiva is generally considered the appropriate control for peri-implantitis, except regarding the cell-ECM interactions.

Optimizing the biodegradability and osteogenesis of biogenic collagen membrane via fluoride-modified polymer-induced liquid precursor process.

Biogenic collagen membranes (BCM) have been widely used in guided bone regeneration (GBR) owing to their biodegradability during tissue integration. However, their relatively high degradation rate and lack of pro-osteogenic properties limit their clinical outcomes. It is of great importance to endow BCM with tailored degradation as well as pro-osteogenic properties. In this study, a fluoride-modified polymer-induced liquid precursor (PILP) based biomineralization strategy was used to convert the collagen membrane from an organic phase to an apatite-based inorganic phase, thus achieving enhanced anti-degradation performance as well as osteogenesis. As a result, three phases of collagen membranes were prepared. The original BCM in the organic phase induced the mildest inflammatory response and was mostly degraded after 4 weeks. The organic-inorganic mixture phase of the collagen membrane evoked a prominent inflammatory response owing to the fluoride-containing amorphous calcium phosphate (F-ACP) nanoparticles, resulting in active angiogenesis and fibrous encapsulation, whereas the inorganic phase induced a mild inflammatory response and degraded the least owing to the transition of F-ACP particles into calcium phosphate with high crystallinity. Effective control of ACP is key to building novel apatite-based barrier membranes. The current results may pave the way for the development of advanced apatite-based membranes with enhanced barrier performances.

Optimized osteogenesis of biological hydroxyapatite-based bone grafting materials by ion doping and osteoimmunomodulation.

BACKGROUND: Biological hydroxyapatite (BHA)-based bone grafting materials have been widely used for bone regeneration in implant surgery. Much effort has been made in the improvement of their osteogenic property as it remains unsatisfactory for clinical use. Osteoimmunomodulation plays a significant role in bone regeneration, which is highly related to active inorganic ions. Therefore, attempts have been made to obtain osteoimmunomodulatory BHA-based bone grafting materials with optimized osteogenic property by ion doping. OBJECTIVE: To summarize and discuss the active inorganic ions doped into BHA and their effects on BHA-based bone grafting materials. METHOD: A literature search was performed in databases including Google Scholar, Web of Science and PubMed, with the elementary keywords of "ion doped" and "biological hydroxyapatite", as well as several supplementary keywords. All document types were included in this search. The searching period and language were not limited and kept updated to 2022. RESULTS: A total of 32 articles were finally included, of which 32 discussed the physiochemical properties of BHA-based biomaterials, while 12 investigated their biological features in vitro, and only three examined their biological performance in vivo. Various ions were doped into BHA, including fluoride, zinc, magnesium and lithium. Such ions improved the biological performance of BHA-based biomaterials, which was attributed to their osteoimmunomodulatory effect. CONCLUSION: The doping of active inorganic ions is a reliable strategy to endow BHA-based biomaterials with osteoimmunomodulatory property and promote bone regeneration. Further studies are still in need to explore more ions and their effects in the crosstalk between the skeletal and immune systems.

Improving hard metal implant and soft tissue integration by modulating the "inflammatory-fibrous complex" response.

Soft tissue integration is one major difficulty in the wide applications of metal materials in soft tissue-related areas. The inevitable inflammatory response and subsequent fibrous reaction toward the metal implant is one key response for metal implant-soft tissue integration. It is of great importance to modulate this inflammatory-fibrous response, which is mainly mediated by the multidirectional interaction between fibroblasts and macrophages. In this study, macrophages are induced to generate M1 and M2 macrophage immune microenvironments. Their cytokine profiles have been proven to have potentially multi-regulatory effects on fibroblasts. The multi-reparative effects of soft tissue cells (human gingival fibroblasts) cultured on metal material (titanium alloy disks) in M1 and M2 immune microenvironments are then dissected. Fibroblasts in the M1 immune microenvironment tend to aggravate the inflammatory response in a pro-inflammatory positive feedback loop, while M2 immune microenvironment enhances multiple functions of fibroblasts in soft tissue integration, including soft tissue regeneration, cell adhesion on materials, and contraction to immobilize soft tissue. Enlighted by the close interaction between macrophages and fibroblasts, we propose the concept of an "inflammatory-fibrous complex" to disclose possible methods of precisely and effectively modulating inflammatory and fibrous responses, thus advancing the development of metal soft tissue materials.

"Brain-inspired intelligence" in dental implant decision-making / 口腔疾病防治

@#At present, implant surgery robots have basically achieved "surgical intelligence", but "brain-inspired intelligence" of robots is still in the stage of theory and exploration. The formulation of a clinical implantation plan depends on the timing of implantation, implantation area, bone condition, surgical procedure, patient factors, etc., which need to evaluate the corresponding clinical decision indicators and clinical pathways. Inspired by evidence-based medicine and the potential of big data and deep learning, combined with the data characteristics of clinical decision indicators and clinical pathways that can be quantitatively or qualitatively analyzed, this review simulates the cognitive behavior and neural mechanisms of the human brain and proposes a feasible brain-inspired intelligence scheme by predicting the decision indices and executing clinical pathways intelligently, that is, "select clinical indicators and clarify clinical pathways -- construct database -- use deep learning to intelligently predict decision indicators -- intelligent execution of clinical pathways -- brain-inspired intelligence of implant decision-making". Combined with the previous research results of our team, this review also describes the process of realization of brain-inspired intelligence for immediate implant timing decisions, providing an example of the comprehensive realization of brain-inspired intelligence of implant surgery robots in the future. In the future, how to excavate and summarize other clinical decision factors and select the best way to realize the automatic prediction of evidence-based clinical indicators and pathways and finally realize the complete intellectualization of clinical diagnosis and treatment processes will be one of the directions that dental clinicians need to strive for.

Placement accuracy and primary stability of implants in the esthetic zone using dynamic and static computer-assisted navigation: A retrospective case-control study.

STATEMENT OF PROBLEM: Both the placement accuracy and primary stability of implants are important to implant therapy in the esthetic zone. The effect of dynamic and static computer-assisted navigation on the primary stability of implants in the esthetic zone remains uncertain. PURPOSE: The purpose of this case-control study was to investigate the effect of dynamic and static computer-assisted navigation on the placement accuracy and primary stability of implants in the esthetic zone. MATERIAL AND METHODS: Partially edentulous participants who received at least 1 implant in the anterior maxilla using either fully guided static or dynamic computer-assisted implant surgery (s-CAIS, d-CAIS) from January 2020 to February 2022 were screened. Participant demographic information, timing of implant placement, primary stability represented by the insertion torque value (ITV) in Ncm, and implant survival were collected from the treatment record. Bone quality at the implant sites was determined according to the Lekholm and Zarb classification. The accuracy of implant placement represented by the linear (platform: Dpl, mm; apex: Dap, mm) and angular deviations (axis: Dan, degree) between the planned and placed implants was evaluated based on the preoperative surgical plan and postoperative cone beam computed tomography (CBCT) data. A statistical analysis of the data was completed by using the chi-square, Fisher exact, Student t, and Mann-Whitney U tests (α=.05). RESULTS: A total of 32 study participants (38 implants) were included. The groups of s-CAIS (16 participants, 18 implants) and d-CAIS (16 participants, 20 implants) were statistically comparable in sex (P=.072), age (P=.548), bone quality (P=.671), and timing of implant placement (P=.719). All implants survived during an average follow-up period of 13 months. The d-CAIS group showed close linear deviations (Dpl 1.07 ±0.57 mm, Dap 1.26 ±0.53 mm) but lower angular deviation (Dan 2.14 ±1.20 degrees) and primary stability (ITV 25.25 ±7.52 Ncm) than the s-CAIS group (Dpl 0.92 ±0.46 mm, Dap 1.31 ±0.43 mm, Dan 3.31 ±1.61 degrees, ITV 30.56 ±11.23 Ncm, PDpl=.613, PDap=.743, PDan=.016, PITV=.028). CONCLUSIONS: Comparable linear positioning accuracy and higher angular deviation were found for implants placed in the esthetic zone by using s-CAIS than when using d-CAIS. Higher primary stability of implants may be achieved by using s-CAIS, as s-CAIS seemed to have higher osteotomy accuracy than d-CAIS.