Spatiotemporal controlled released hydrogels for multi-system regulated bone regeneration.

Bone defect is one of the urgent problems to be solved in clinics, and it is very important to construct efficient scaffold materials to facilitate bone tissue regeneration. Hydrogels, characterized by their unique three-dimensional network structure, serve as excellent biological scaffold materials. Their internal pores are capable of loading osteogenic drugs to expedite bone formation. The rate and quality of new bone formation are intimately linked with immune regulation and vascular remodeling. The strategic sequential release of drugs to balance inflammation and regulate vascular remodeling is crucial for initiating the osteogenic process. Through the design of hydrogel microstructures, it is possible to achieve sequential drug release and the drug action time can be prolonged, thereby catering to the multi-systemic collaborative regulation needs of osteosynthesis. The drug release rate within the hydrogel is governed by swelling control systems, physical control systems, chemical control systems, and environmental control systems. Utilizing these control systems to design hydrogel materials capable of multi-drug delivery optimizes the construction of the bone microenvironment. Consequently, this facilitates the spatiotemporal controlled released of drugs, promoting bone tissue regeneration. This paper reviews the principles of the controlled release system of various sustained-release hydrogels and the advancements in research on hydrogel multi-drug delivery systems for bone tissue regeneration.

Mild Thermotherapy-Assisted GelMA/HA/MPDA@Roxadustat 3D-Printed Scaffolds with Combined Angiogenesis-Osteogenesis Functions for Bone Regeneration.

Early reconstruction of the vascular network is a prerequisite to the effective treatment of substantial bone defects. Traditional 3D printed tissue engineering scaffolds designed to repair large bone defects do not effectively regenerate the vascular network, and rely only on the porous structure within the scaffold for nutrient transfer and metabolic waste removal. This leads to delayed bone restoration and hence functional recovery. Therefore, strategies for generation scaffolds with the capacity to efficiently regenerate vascularization should be developed. This study loads roxarestat (RD), which can stabilize HIF-1α expression in a normoxic environment, onto the mesopore polydopamine nanoparticles (MPDA@RD) to enhance the reconstruction of vascular network in large bone defects. Subsequently, MPDA@RD is mixed with GelMA/HA hydrogel bioink to fabricate a multifunctional hydrogel scaffold (GHM@RD) through 3D printing. In vitro results show that the GHM@RD scaffolds achieve good angiogenic-osteogenic coupling by activating the PI3K/AKT/HSP90 pathway in BMSCs and the PI3K/AKT/HIF-1α pathway in HUVECs under mild thermotherapy. In vivo experiments reveal that RD and mild hyperthermia synergistically induce early vascularization and bone regeneration of critical bone defects. In conclusion, the designed GHM@RD drug delivery scaffold with mild hyperthermia holds great therapeutic value for future treatment of large bone defects.

Isolation, identification and osteogenic capability analysis of mesenchymal stem cells derived from different layers of human maxillary sinus membrane.

AIM: To discover the populations of mesenchymal stem cells (MSCs) derived from different layers of human maxillary sinus membrane (hMSM) and evaluate their osteogenic capability. MATERIALS AND METHODS: hMSM was isolated into a monolayer using the combined method of physical separation and enzymatic digestion. The localization of MSCs in hMSM was performed by immunohistological staining and other techniques. Lamina propria layer-derived MSCs (LMSCs) and periosteum layer-derived MSCs (PMSCs) from hMSM were expanded using the explant cell culture method and identified by multilineage differentiation assays, colony formation assay, flow cytometry and so on. The biological characteristics of LMSCs and PMSCs were compared using RNA sequencing, reverse transcription and quantitative polymerase chain reaction, immunofluorescence staining, transwell assay, western blotting and so forth. RESULTS: LMSCs and PMSCs from hMSMs were both CD73-, CD90- and CD105-positive, and CD34-, CD45- and HLA-DR-negative. LMSCs and PMSCs were identified as CD171+/CD90+ and CD171-/CD90+, respectively. LMSCs displayed stronger proliferation capability than PMSCs, and PMSCs presented stronger osteogenic differentiation capability than LMSCs. Moreover, PMSCs could recruit and promote osteogenic differentiation of LMSCs. CONCLUSIONS: This study identified and isolated two different types of MSCs from hMSMs. Both MSCs served as good potential candidates for bone regeneration.

Case report and literature review: autonomous robotic system assisted palatal implantation at an anterior teeth site compromised by periapical cyst.

Background: Immediate implant placement (IIP), which preserves gingival height and papilla shape while simultaneously accelerating the implant treatment period, has become a popular method due to its commendable clinical outcomes. Nonetheless, deploying immediate implants demands specific preconditions concerning the remaining alveolar bone. This poses a challenge to the accuracy of implant surgery. Case presentation: In this report, we present the case of a 60-year-old woman with a left upper anterior tooth crown dislodged for over a month. Cone beam computed tomography (CBCT) revealed the absence of a labial bone wall on tooth 22, a remaining 1 mm bone wall on the labial side of the root apex, and a 17.2 mm*8.9 mm*4.7 mm shadow in the periapical region of the root apices of teeth 21 and 22, with the narrowest width on the sagittal plane being approximately 5 mm. After the surgeon removed the cyst, they completed the subsequent implantation surgery using an autonomous robot in a challenging aesthetic area. This method circumvented the potential exposure of the screw thread on the labial implant surface, assured initial implant stability. Conclusion: Five months after the operation, the dental crown was restored. The implant remained stable, with yielding notable clinical results. To the best of our knowledge, this clinical case is the first to report the feasibility and precision of immediate implantation in anterior teeth site with periapical cyst removal, performed by an autonomous robotic surgical system. Autonomous robots exhibit exceptional accuracy by accurately controlling axial and angular errors. It can improve the accuracy of implant surgery, which may become a key technology for changing implant surgery. However, further clinical trials are still needed to provide a basis for the rapid development of robotic surgery field.

Black Phosphorus - A Rising Star in the Antibacterial Materials.

Antibiotics are the most commonly used means to treat bacterial infection at present, but the unreasonable use of antibiotics induces the generation of drug-resistant bacteria, which causes great problems for their clinical application. In recent years, researchers have found that nanomaterials with high specific surface area, special structure, photocatalytic activity and other properties show great potential in bacterial infection control. Among them, black phosphorus (BP), a two-dimensional (2D) nanomaterial, has been widely reported in the treatment of tumor and bone defect due to its excellent biocompatibility and degradability. However, the current theory about the antibacterial properties of BP is still insufficient, and the relevant mechanism of action needs to be further studied. In this paper, we introduced the structure and properties of BP, elaborated the mechanism of BP in bacterial infection, and systematically reviewed the application of BP composite materials in the field of antibacterial. At the same time, we also discussed the challenges faced by the current research and application of BP, which laid a solid theoretical foundation for the further study of BP in the future.

Amplification of oxidative damage using near-infrared II-mediated photothermal/thermocatalytic effects for periodontitis treatment.

Periodontitis is a biofilm-related disease characterized by damage to the periodontal tissue and the development of systemic diseases. However, treatment of periodontitis remains unsatisfactory, especially with deep-tissue infections. This study describes rationally designed multifunctional photothermocatalytic agents for near-infrared-II light-mediated synergistic antibiofilm treatment, through modification of Lu-Bi2Te3 with Fe3O4 and poly(ethylene glycol)-b-poly(l-arginine) (PEG-b-PArg). Notably, 1064-nm laser irradiation led to photothermal/thermocatalytic effects, resulting in the synergistic generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consequent damage to the biofilm. This treatment was based on the thermoelectric and photothermal conversion properties of Lu-Bi2Te3, the peroxidase-like catalytic capacity of Fe3O4, and the guanidinium polymer, PEG-b-PArg. Oxidative damage to biofilm was further enhanced by H2O2, resulting in the effective elimination of biofilm both in vitro and in vivo. These findings suggest that this synergistic therapeutic strategy is effective for the clinical treatment of periodontitis. STATEMENT OF SIGNIFICANCE: The current treatment for periodontitis involves time-consuming and labor-intensive clinical scaling of the teeth. The present study is the first to assess the efficacy of a photothermal catalyst for periodontitis treatment. This used near-infrared-II light at 1064 nm to induce oxidative damage in the biofilm, resulting in its degradation. The synergistic photothermal/thermoelectric effect produced deep tissue penetration and was well tolerated, and can kill the biofilm formed by periodontitis pathogens up to 5 orders of magnitude, effectively treating the biofilm-induced periodontitis.

3D printing of MXene composite hydrogel scaffolds for photothermal antibacterial activity and bone regeneration in infected bone defect models.

The repair of infected bone defects with irregular shapes is still a challenge in clinical work. Infected bone defects are faced with several major concerns: the complex shapes of bone defects, intractable bacterial infection and insufficient osseointegration. To solve these problems, we developed a personalized MXene composite hydrogel scaffold GelMA/ß-TCP/sodium alginate (Sr2+)/MXene (Ti3C2) (GTAM) with photothermal antibacterial and osteogenic abilities by 3D printing. In vitro, GTAM scaffolds could kill both Gram-positive and Gram-negative bacteria by NIR irradiation due to the excellent photothermal effects of MXene. Furthermore, rat bone marrow mesenchymal stem cells were mixed into GTAM bioinks for 3D bioprinting. The cell-laden 3D printed GTAM scaffolds showed biocompatibility and bone formation ability depending on MXene, crosslinked Sr2+, and ß-TCP. In vivo, we implanted 3D printed GTAM scaffolds in S. aureus-infected mandible defects of rats with NIR irradiation. GTAM scaffolds could accelerate the healing of infection and bone regeneration, and play synergistic roles in antibacterial and osteogenic effects. This study not only provides a strategy for the precise osteogenesis of infected bone defects, but also broadens the biomedical applications of MXene photothermal materials.

Flapless osteotome-mediated sinus floor elevation using platelet-rich fibrin versus lateral approach using deproteinised bovine bone mineral for residual bone height of 2-6 mm: A randomised trial.

OBJECTIVES: To evaluate patient-reported outcomes and radiographic results of simultaneous implant placement in severely atrophic maxilla using flapless endoscope-assisted osteotome sinus floor elevation with platelet-rich fibrin (PRF), also defined as PESS, and to compare the results with those of lateral sinus floor elevation (LSFE). METHODS: Patients with a residual bone height (RBH) of 2-6 mm were included in a randomised controlled trial. PESS was performed with PRF as the sole grafting material. LSFE was performed using deproteinised bovine bone matrix. Patient-reported outcomes were recorded on a visual analogue scale (VAS-pain) and visual rating scale (VRS-swelling and VRS-willingness). Peri-implant bone height (PBH), bone mineral density (BMD) and sinus grafting remodelling index were measured using CBCT immediately postoperatively and 3rd, 6th and 18th months post-surgery. RESULTS: The study population consisted of 20 patients in each group. The RBH of two groups averaged 3.35 ± 0.79 mm and 2.92 ± 0.63 mm with no significant difference (p > .05). VAS-pain was 18.0 (IR 15.0-22.5) and 35.0 (IR 32.5-37.0) in the PESS and LSFE groups, respectively (p < .01). VAS-pain decreased with time in both groups. VRS-swelling was lower in the PESS group than LSFE group. VRS-willingness was higher in the PESS group than LSFE group (p < .01). At 18 months post-surgery, the marginal bone loss was 0.60 ± 0.25 mm and 0.69 ± 0.35 mm in the two groups with no significant difference (p = .52). CONCLUSIONS: Within the limitations of this study, PESS was associated with lower postoperative morbidity and was more tolerable than LSFE. PESS could be a reliable procedure for sinus floor elevation in patients with insufficient RBH.

Screening for odorant receptor genes expressed in Aedes aegypti involved in host-seeking, blood-feeding and oviposition behaviors.

BACKGROUND: Aedes aegypti is one of the most important vectors of zoonotic diseases worldwide, and its survival and reproductive processes depend heavily on its olfactory system. In this study, the expression levels of all odorant receptor (OR) genes of Ae. aegypti were explored during different physiological periods to identify olfactory genes that may be associated with mosquito blood-feeding and the search for oviposition sites. METHODS: Four experimental groups, consisting of Ae. aegypti males, pre-blood-feeding females, post-blood-feeding females and post-oviposition females, were established. A total of 114 pairs of primers targeting all messenger RNA encoded by OR genes were designed based on the whole genome of Ae. aegypti. The expression of OR genes was evaluated by real-time fluorescence quantitative PCR for relative quantification and the comparison of differences between groups. RESULTS: A total of 53 differentially expressed OR genes were identified between males and females in Ae. aegypti antennae. Also, eight, eight and 13 differentially expressed OR genes were identified in pre- versus post-blood-feeding females, in pre- versus post-oviposition females and in post-blood-feeding versus post-oviposition females, respectively. In addition, 16 OR genes were significantly differentially expressed in multiple physiological periods of the mosquitoes. CONCLUSIONS: A large number of ORs with significant intergroup differences and high expression levels were screened in this study. Some of these genes are reported for the first time, providing possible targets for the development of mosquito control pathways based on the olfactory system.

Immediate implant placement in combination with platelet rich-fibrin into extraction sites with periapical infection in the esthetic zone: A case report and review of literature.

BACKGROUND: In this case, platelet-rich fibrin (PRF) was added to guided tissue regeneration as a biomaterial in proper order for immediate planting in aesthetic area with periapical infection. CASE SUMMARY: With the history of endodontic failure in maxillary central incisor, a 34-year-old female patient required the extraction of maxillary anterior residual root and immediate implantation. Cone beam computed tomography and clinical observation were used to assess the regeneration of soft and bone tissue. Before operation, cone beam computed tomography showed the anterior residual root had serious periapical periodontitis with insufficient labial bone in the aesthetic zone. The patient underwent immediate implant placement and reconstruction of the bone substitution by modified guided bone regeneration. The barrier was a three-layer structure of PRF-collagen membrane-PRF that covered the mixture of PRF and Bio-Oss to promote both osteogenesis and soft tissue healing. At 6 mo postoperatively, the definitive crown was placed after accomplished finial impression. One-year follow-up showed a satisfactory aesthetic effect with no obvious absorption of the labial bone and soft tissue. CONCLUSION: The use of PRF in combination with guided bone regeneration can serve as a reliable and simple adjuvant for immediate implanting in infected socket and result in a stable osteogenic effect with good aesthetic outcome.

Endoscope-Assisted Maxillary Sinus Floor Elevation with Platelet-Rich Fibrin Grafting and Simultaneous Implant Placement: A Prospective Clinical Trial.

PURPOSE: To evaluate the clinical and radiographic outcomes of endoscope-assisted maxillary sinus floor elevation with platelet-rich fibrin grafting and simultaneous implant placement (PESS) in atrophic maxillae. MATERIALS AND METHODS: Twenty-three implants were placed to rehabilitate atrophic maxillae. Patient satisfaction was measured with a visual analog scale (VASpain). CBCT was taken to assess the bone changes for the elevated sites. RESULTS: Twenty-two of 23 implants fulfilling the survival criteria represented a 1-year survival rate of 95.65%. The VASpain score decreased with time. The residual bone height was 4.45 ± 1.44 mm. The elevation height was 6.72 ± 1.84 mm. The definitive restoration was completed in the 4th month postsurgery. The peri-implant bone level value was 6.04 ± 2.30 mm, 6.32 ± 2.25 mm, and 6.71 ± 1.97 mm at the 3rd, 9th, and 15th month postsurgery. The crestal bone level value decreased by 0.22 ± 0.56 mm from the 3rd month to the 15th month postsurgery (P > .05). Bone mineral density increased with time at the neck, middle, and root site of implant. CONCLUSION: PESS in the maxilla resulted in predictable peri-implant bone formation. This strategy is a relatively safe and effective approach with less invasion, which provides new insights into the choice of implant treatment plans.

Effects of quercetin on human oral keratinocytes during re-epithelialization: An in vitro study.

BACKGROUND: The width of keratinized mucosa plays an important role in esthetic and functional outcomes of dental implants. Lack of keratinized mucosa may lead to poor oral hygiene and greater soft-tissue recession. This study aimed at assessing the potential of quercetin in promoting human oral keratinocyte (HOK) proliferation and re-epithelialization in vitro. MATERIALS AND METHODS: HOK were detected in the absence or presence of test substances. The Cell Counting Kit-8 was used to assess cell viability and proliferation capacity. Re-epithelization was assessed using a keratinocyte monolayer scratch assay. Cell migration was monitored via Transwell chambers. Porphyromonas gingivalis lipopolysaccharide was used to stimulate keratinocytes for mimicking the inflammatory situation. mRNA expression of inflammatory cytokines (interleukin-1beta, IL-1ß and tumor necrosis factor alpha, TNF-α), cell adhesion molecules (Integrin-α6, Integrin-ß4), and growth factors (transforming growth factor beta 1,TGF-ß1 and transforming growth factor beta 3, TGF-ß3) were estimated using RT-qPCR. Protein contents of TGF-ß1 and TGF-ß3 were investigated by enzyme-linked immunosorbent assay. RESULTS: Multiplex analysis revealed that quercetin enhances HOK proliferation via an upregulation of adhesion molecules (Integrin-α6ß4). Additionally, re-epithelialization rate was significantly greater in the presence of quercetin than in the control (P < 0.01). Furthermore, 20 µM of quercetin increases both mRNA and protein levels of TGF-ß3 under basal and wound conditions without affecting TGF-ß1 production. Expressions of pro-inflammatory cytokines were downregulated by quercetin treatment. CONCLUSION: Quercetin promotes HOKs proliferation and oral re-epithelialization in vitro.

Sineoculis homeobox homolog 1 protein as an independent biomarker for gastric adenocarcinoma.

Sine oculis homeobox homolog 1 (SIX1) protein is a member of the homeobox transcription factor family. Overexpression of SIX1 contributes to cancer progression and is associated with adverse outcomes in various cancer types including breast, ovarian, uterine cervical and liver. To investigate the clinicopathological significance of SIX1 protein expression in gastric adenocarcinomas (GAC), localization of the SIX1 protein was determined in MKN-1, a gastric cancer cell line, using immunofluorescence (IF) staining; SIX1 mRNA level was detected in fresh tissues of GAC and normal gastric mucosa using quantitative real-time polymerase chain reaction (qRT-PCR); and SIX1 protein expression was assessed in 163 GAC, 35 gastric dysplasia and 26 normal gastric mucosa using immunohistochemical (IHC) staining. Correlations between SIX1 protein expression and pathological parameters of GAC were analyzed using Chi-square tests, differences in survival curves were analyzed using log-rank tests, and multivariate survival analysis was performed using the Cox proportional hazards regression model. SIX1 protein showed a mainly cytoplasmic staining pattern in GAC using IF and IHC staining. The positive SIX1 protein expression rate was 80.4% in GAC, which was significantly higher than in either gastric dysplasia (45.7%) or normal gastric mucosa (26.9%) (P<0.01). qRT-PCR data also confirmed increased levels of SIX1 mRNA expression in GAC compared with the normal gastric mucosa in fresh tissues. In addition, the strongly positive SIX1 protein expression rate was significantly correlated with clinical stage, lymph node metastasis and serosal invasion of GAC (P<0.01 or P<0.05), while there was no association with gender, age, tumor size, Lauren classification or histological types of GAC. Notably, strongly positive signals were frequently observed in tumor blood vessels and/or lymphatic vessels. GAC patients with high expression of the SIX1 had shorter overall and disease-free survival rates than those with low SIX1 protein expression (P<0.01). Furthermore, using multivariate analysis, SIX1 protein expression was found to be an independent risk factor for survival in patients with GAC along with clinical stage and serosal invasion (P<0.01). In conclusion, SIX1 protein expression status may be an independent biomarker for prognostic evaluation of GAC.