Multi-Mechanism Antibacterial Strategies Enabled by Synergistic Activity of Metal-Organic Framework-Based Nanosystem for Infected Tissue Regeneration.

Drug-resistant bacterial infection impairs tissue regeneration and is a challenging clinical problem. Metal-organic frameworks (MOFs)-based photodynamic therapy (PDT) opens up a new era for antibiotic-free infection treatment. However, the MOF-based PDT normally encounters limited photon absorbance under visible light and notorious recombination of photogenerated holes and electrons, which significantly impede their applications. Herein, a MOFs-based nanosystem (AgNPs@MOFs) with enhanced visible light response and charge carrier separation is developed by modifying MOFs with silver nanoparticles (AgNPs) to improve PDT efficiency. The AgNPs@MOFs with enhanced photodynamic performance under visible light irradiation mainly disrupt bacteria translation process and the metabolism of purine and pyrimidine. In addition, the introduction of AgNPs endows nanosystems with chemotherapy ability, which causes destructive effect on bacterial cell membrane, including membrane ATPase protein and fatty acids. AgNPs@MOFs show excellent synergistic drug-resistant bacterial killing efficiency through multiple mechanisms, which further restrain bacterial resistance. In addition, biocompatible AgNPs@MOFs pose potential tissue regeneration ability in both Methicillin-resistant Staphylococcus aureus (MRSA)-related soft and hard tissue infection. Overall, this study provides a promising perspective in the exploration of AgNPs@MOFs as nano antibacterial medicine against drug-resistant bacteria for infected tissue regeneration in the future.

Biomechanical behavior analysis of four types of short implants with different placement depths using the finite element method.

STATEMENT OF PROBLEM: The clinical application of short implants has been increasing. However, studies on the marginal bone loss of short implants are sparse, and clinicians often choose short implants based on their own experience rather than on scientific information. PURPOSE: The purpose of this finite element analysis study was to evaluate the microstrain-stress distribution in the peri-implant bone and implant components for 4 types of short implants at different placement depths of platform switching. MATERIAL AND METHODS: By using short implants as prototypes, 4 short implant models were 1:1 modeled. The diameter and length of the implants were 5×5, 5×6, 6×5, and 6×6 mm. The restoration was identical for all implants. Three different depths of implant platform switching were set: equicrestal, 0.5-mm subcrestal, and 1-mm subcrestal. The models were then assembled and assigned an occlusal force of 200 N (vertical or 30-degree oblique). A finite element analysis was carried out to evaluate the maximum equivalent elastic strain and von Mises stress in the bone and the stress distribution in the implant components. RESULTS: The 5×5 implant group showed the largest intraosseous strain (21.921×103 µÎµ). A 1-mm increase in implant diameter resulted in a 17.1% to 37.4% reduction in maximum intraosseous strain when loaded with oblique forces. The strain in the bone tended to be much smaller than the placement depth at the equicrestal and 0.5-mm subcrestal positions than that at the 1-mm subcrestal position, especially under oblique force loading, with an increase of approximately 37.4% to 81.8%. In addition, when the cortical bone thickness was less than 4 mm, 5×6 implants caused significantly higher intraosseous stresses than 6×6 implants. CONCLUSIONS: Large implant diameters, rather than long implants, led to reduced intraosseous strain, especially under oblique loading. Regarding the implant platform switching depth, the short implant showed small intraosseous strains when the platform switching depth was equicrestal or 0.5-mm subcrestal.

pH-Triggered Size-Tunable Silver Nanoparticles: Targeted Aggregation for Effective Bacterial Infection Therapy.

The rapid spread of drug-resistant pathogens threatens human health. To address the current antibacterial dilemma, the development of antibiotic-free strategies using nanotechnology is imperative. In this study, silver nanoparticles (Ag-P&C NPs) with pH-sensitive charge reversal and self-aggregation capacities are successfully synthesized. In the acidic microenvironment of bacterial biofilms, protonation of the surface peptide enhances the affinity of Ag-P&C NPs for bacteria, which can make Ag-P&C NPs prone to target and penetrate into biofilms, and the self-aggregated capacity helps Ag-P&C NPs remain in biofilms for a long time to disrupt bacterial biofilm formation. In addition, biocompatible Ag-P&C NPs are utilized in three types of bacteria-infected animal models. They exhibit an excellent performance in killing bacteria, inhibiting plaque biofilms, and ameliorating inflammatory responses. In conclusion, this study offers new insights into antibiotic-free antibacterial strategies, and exhibits promising application prospects.

Interimplant papilla reconstruction at second-stage surgery: A technique.

Reconstructing an esthetic interimplant papilla remains challenging with implant-supported restorations, especially for patients with a thin gingival biotype. This technique report describes a modified approach to rebuilding an interimplant papilla by joining 2 elevated connective tissue flaps at the second-stage surgery.

A Modified Transalveolar Sinus Floor Elevation Approach With a Bilaterally Enlarged Osteotomy.

Sinus floor elevation is the most commonly used method for vertical bone augmentation in the maxillary posterior area. This clinical report describes a modified transalveolar approach to elevate the Schneiderian membrane when placing implants on a severely resorbed maxillary posterior ridge with a buccal-palatal width of more than 8.0 mm. In this approach, the osteotomy prepared on the crestal is bilaterally enlarged to 8.0-10.0 mm. The enlarged osteotomies provide better access, allowing instruments to be in direct contact with the bone of the sinus floor and thus elevate the Schneiderian membrane with a reduced risk of perforation.

A Combined Lateral-Crestal Approach of Sinus Floor Elevation: Three Case Reports.

This clinical report describes a combined lateral-crestal approach to elevate the sinus floor when placing implants on a wide maxillary posterior ridge. The buccally enlarged osteotomy broadens the vision of practitioners and facilitates access of instruments in the sinus. Compared with the traditional lateral approach of sinus lift, the proposed technique offers a more conservative treatment modality. A clinical study with sufficient subjects and long-term follow-up is needed to validate the potential and limitations of the proposed technique.

Effects of platelet concentrates on implant stability and marginal bone loss: a systematic review and meta-analysis.

BACKGROUND: Osseointegration is essential for the success and stability of implants. Platelet concentrates were reported to enhance osseointegration and improve implant stability. The purpose of this review is to systematically analyze the effects of platelet concentrates on implant stability and marginal bone loss. METHODS: Two researchers independently performed searches in the following databases (last searched on 21 July 2021): MEDLINE (PubMed), Cochrane Library, EMBASE, and Web of Science. In addition, a manual search was carried out on references of relevant reviews and initially included studies. All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on the application of platelet concentrates in the implant surgery procedure were included. The risk of bias of RCTs and CCTs were assessed with a revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and the risk of bias in non-randomized studies-of interventions (ROBINS-I) tool, respectively. Meta-analyses on implant stability and marginal bone loss were conducted. Researchers used mean difference or standardized mean difference as the effect size and calculated the 95% confidence interval. In addition, subgroup analysis was performed based on the following factors: type of platelet concentrates, method of application, and study design. RESULTS: Fourteen studies with 284 participants and 588 implants were included in the final analysis. 11 studies reported implant stability and 5 studies reported marginal bone level or marginal bone loss. 3 studies had high risk of bias. The meta-analysis results showed that platelet concentrates can significantly increase implant stability at 1 week (6 studies, 302 implants, MD 4.26, 95% CI 2.03-6.49, P < 0.001) and 4 weeks (8 studies, 373 implants, MD 0.67, 95% CI 0.46-0.88, P < 0.001) after insertion, significantly reduced marginal bone loss at 3 months after insertion (4 studies, 95 implants, mesial: MD - 0.33, 95% CI - 0.46 to - 0.20, P < 0.001; distal: MD - 0.38, 95% CI - 0.54 to - 0.22, P < 0.001). However, the improvement of implant stability at 12 weeks after insertion was limited (P = 0.10). Subgroup analysis showed that PRP did not significantly improve implant stability at 1 week and 4 weeks after insertion (P = 0.38, P = 0.17). Platelet concentrates only placed in the implant sites did not significantly improve implant stability at 1 week after insertion (P = 0.20). CONCLUSIONS: Platelet concentrates can significantly improve implant stability and reduce marginal bone loss in the short term. Large-scale studies with long follow-up periods are required to explore their long-term effects and compare effects of different types. TRIAL REGISTRATION: This study was registered on PROSPERO, with the Registration Number being CRD42021270214.

Guided residual root preparation for socket-shield procedures: A clinical report.

Tooth extraction in the esthetic area is usually accompanied by hard- and soft-tissue changes. The socket-shield technique is an effective method for preventing these undesirable changes. However, difficulty in preparing the socket shield and controlling the implant position might increase the complication rate along with the time needed for the surgery, limiting its widespread use. This clinical report demonstrates a digital protocol for accurate and rapid socket-shield preparation and implant placement with surgical guides.

Evaluation of needle movement effect on root canal irrigation using a computational fluid dynamics model.

BACKGROUND: Irrigation is considered to be a critical part of root canal treatment. However, little is known about the effect of needle movement on the irrigation process. Therefore, this study aimed to investigate the influence of the syringe and needle movement on root canal irrigation using a three-dimensional computational fluid dynamics (CFD) numerical model. METHODS: The CFD codes Flow-3D was adopted to simulate the root canal irrigation process with the syringe and needle moving up and down in motions at different amplitudes and frequencies. One stationary needle was adopted to allow comparison with the needles in up-and-down motions. Six cases where the needles were moving up and down with different amplitudes and frequencies were used to investigate the relationships between the motion of needle and irrigation efficacy. RESULTS: The stationary needle gained relatively higher flow velocity and apical pressure all through the irrigation process, while the needles in constant up-and-down motions exhibited lower mean flow velocity and apical pressure. The larger the amplitude, the less mean flow velocity and apical pressure were developed. In addition, the needles moving with different frequencies were similar in the terms of irrigant replacement and apical pressure. CONCLUSIONS: To avoid periapical extrusion accidents while obtaining adequate irrigant replacement, the needle should be moving up and down with a moderate amplitude during manual root canal irrigation; and the motion frequency was not highly relevant in terms of the irrigation efficiency.

An evaluation of fluid distribution at the implant site during implant placement by using a computational fluid dynamics model.

STATEMENT OF PROBLEM: Heat reduction during implant site preparation is critical. However, studies that assess fluid distribution at the implant site by using saline irrigation as the cooling method during osteotomies are lacking. PURPOSE: The purpose of this study was to evaluate the effect of various parameters on fluid distribution at the implant site by using a computational fluid dynamics numerical model and thus predict the cooling effect at the drill site. MATERIAL AND METHODS: The computational fluid dynamics code Flow-3D was adopted to simulate implant site preparation. A 10-mm-deep implant site was prepared by using a 2.2-mm pilot drill, with 4 °C saline sprayed onto the drill from an external injection hole. Different drilling procedures were performed with irrigation volumes of 20, 40, 60, and 80 mL/min at various drill speeds (600, 800, 1000, 1200 rpm) and feed rates (0.5, 1.0, 1.5, 2.0 mm/s), and the fluid distribution under various circumstances was respectively investigated and compared. Data were analyzed by using 1-way ANOVA or the Friedman test according to the normality of the data distribution (P>.05). RESULTS: Below the irrigation volume of 60 mL/min, the saline inside the implant site increased with the irrigation volume (P<.001), but further increase in irrigation volume to 80 mL/min had no significant influence on the fluid distribution (P>.05). The obtained fluid had an inverse relationship with the drill speed under the irrigation volumes 20 and 40 mL/min (P<.001), and deeper areas received less cooling under 20 mL/min (P<.001). However, no significant differences were observed under 60 and 80 mL/min (P>.05). In addition, the variation of feed rate had no significant effect on the mean fluid fraction for all the tested groups (P>.05). CONCLUSIONS: The fluid distribution at the implant site could be affected by the irrigation volume and drill speed but was not correlated with the feed rate.

A Systematic Review of the Survival and Complication Rates of All-Ceramic Resin-Bonded Fixed Dental Prostheses.

PURPOSE: The aim of this systematic review was to investigate the survival and complication rates of all-ceramic resin-bonded fixed dental prostheses (RBFDPs). MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied. A systematic search was conducted by an electronic search in PubMed, EMBASE, Cochrane Library, and CNKI databases complemented by a manual search. Only clinical studies on all-ceramic RBFDPs with a mean follow-up period of at least 3 years qualified for data analyses. RESULTS: Among 1503 screened articles, one randomized controlled trial (RCT) and seven prospective or retrospective cohort studies were included in this study. The estimated 5-year survival rate of all-ceramic RBFDPs was 91.2%. Debonding and framework fracture were the two most frequent technical complications, and the estimated 5-year debonding rate and fracture rate were 12.2% and 4.8%, respectively. Additionally, cantilevered all-ceramic RBFDPs had a higher survival rate (p < 0.01), lower debonding rate, (p < 0.05), and fracture rate (p < 0.01) compared with two-retainer all-ceramic RBFDPs. Zirconia ceramic RBFDPs had a lower incidence of failure but a higher debonding rate compared with glass-ceramic RBFDPs (p < 0.01). CONCLUSION: Within the limitations of this systematic review, although all-ceramic RBFDPs have a favorable 5-year survival rate, this rate cannot represent the complete success of the treatment, since it may include typical complications such as debonding and fractures. There is an urgent need for long-term clinical studies, especially for well-designed RCTs on all-ceramic RBFDPs.

Effects of Hyperlipidemia on Osseointegration of Dental Implants and Its Strategies.

Hyperlipidemia refers to the abnormal increase in plasma lipid level exceeding the normal range. At present, a large number of patients require dental implantation. However, hyperlipidemia affects bone metabolism, promotes bone loss, and inhibits the osseointegration of dental implants through the mutual regulation of adipocytes, osteoblasts, and osteoclasts. This review summarized the effects of hyperlipidemia on dental implants and addressed the potential strategies of dental implants to promote osseointegration in a hyperlipidemic environment and to improve the success rate of dental implants in patients with hyperlipidemia. We summarized topical drug delivery methods to solve the interference of hyperlipidemia in osseointegration, which were local drug injection, implant surface modification and bone-grafting material modification. Statins are the most effective drugs in the treatment of hyperlipidemia, and they also encourage bone formation. Statins have been used in these three methods and have been found to be positive in promoting osseointegration. Directly coating simvastatin on the rough surface of the implant can effectively promote osseointegration of the implant in a hyperlipidemic environment. However, the delivery method of this drug is not efficient. Recently, a variety of efficient methods of simvastatin delivery, such as hydrogels and nanoparticles, have been developed to boost bone formation, but few of them were applied to dental implants. Applicating these drug delivery systems using the three aforementioned ways, according to the mechanical and biological properties of materials, could be promising ways to promote osseointegration under hyperlipidemic conditions. However, more research is needed to confirm.

Type H blood vessels in coupling angiogenesis-osteogenesis and its application in bone tissue engineering.

One specific capillary subtype, termed type H vessel, has been found with unique functional characteristics in coupling angiogenesis with osteogenesis. Researchers have fabricated a variety of tissue engineering scaffolds to enhance bone healing and regeneration through the accumulation of type H vessels. However, only a limited number of reviews discussed the tissue engineering strategies for type H vessel regulation. The object of this review is to summary the current utilizes of bone tissue engineering to regulate type H vessels through various signal pathways including Notch, PDGF-BB, Slit3, HIF-1α, and VEGF signaling. Moreover, we give an insightful overview of recent research progress about the morphological, spatial and age-dependent characteristics of type H blood vessels. Their unique role in tying angiogenesis and osteogenesis together via blood flow, cellular microenvironment, immune system and nervous system are also summarized. This review article would provide an insight into the combination of tissue engineering scaffolds with type H vessels and identify future perspectives for vasculized tissue engineering research.

Alginate-based biomaterial-mediated regulation of macrophages in bone tissue engineering.

Many studies in the bone tissue engineering field have focused on the interactions between materials and bone marrow stem cells. With the development of osteoimmunology, the immune cells' essential role in biomaterial-mediated osteogenesis has increasingly been recognized. As a promising therapeutic candidate for bone defects due to their prominent biocompatibility, tuneability, and versatility, it is necessary to develop alginate-based biomaterials that can regulate immune cells, especially macrophages. Moreover, modified alginate-based biomaterials may facilitate better regulation of macrophage phenotypes by the newly endowed physicochemical properties, including stiffness, porosity, hydrophilicity, and electrical properties. This review summarizes the role of macrophages in bone regeneration and the recent research progress related to the effects of alginate-based biomaterials on macrophages applied in bone tissue engineering. This review also emphasizes the strategies adopted by material design to regulate macrophage phenotypes, the corresponding macrophage responses, and their contribution to osteogenesis.

Gold nanoparticles: promising biomaterials for osteogenic/adipogenic regulation in bone repair.

Bone defects are a common bone disease, which are usually caused by accidents, trauma and tumors. However, the treatment of bone defects is still a great clinical challenge. In recent years, research on bone repair materials has continued with great success, but there are few reports on the repair of bone defects at a high lipid level. Hyperlipidemia is a risk factor in the process of bone defect repair, which has a negative impact on the process of osteogenesis, increasing the difficulty of bone defect repair. Therefore, it is necessary to find materials that can promote bone defect repair under the condition of hyperlipidemia. Gold nanoparticles (AuNPs) have been applied in the fields of biology and clinical medicine for many years and developed to modulate osteogenic differentiation and adipogenic differentiation. In vitro and vivo studies displayed that they promoted bone formation and inhibited fat accumulation. Further, the metabolism and mechanisms of AuNPs acting on osteogenesis/adipogenesis were partially revealed by researchers. This review further clarifies the role of AuNPs in osteogenic/adipogenic regulation during the process of osteogenesis and bone regeneration by summarizing the related in vitro and in vivo research, discussing the advantages and challenges of AuNPs and highlighting several possible directions for future research, with the aim to provide a new strategy for dealing with bone defects in hyperlipidemic patients.

Rapid Additive Manufacturing of a Superlight Obturator for Large Oronasal Fistula in Pediatric Patient.

This study developed a novel digital workflow to fabricate a 3D printed hollow obturator for the prosthetic reconstruction of palatal fistula. It will provide cleft surgeons and therapists a choice for treating children with large palatal fistula before the appropriate age for surgical reconstruction. Laryngoscope, 133:1507-1512, 2023.

Vascular and lymphatic heterogeneity and age-related variations of dental pulps.

OBJECTIVES: Dental pulp tissue is highly vascularized. However, age-related vascular changes of the dental pulp in mice and humans remain poorly understood. We modified a novel tissue clearing method, mapped the vasculature, pericytes, and perivascular matrix in the dental pulp via high-resolution 3D imaging. METHODS: We isolated young and aged pulps from mouse teeth, and mapped vasculature through a high-resolution thick frozen sections imaging method and a modified tissue clearing method. Human dental pulps were also mapped for vasculature studying. Furthermore, young and aged human dental pulps were collected and were compared with mouse pulps through RNA- sequencing. RESULTS: Five vascular subtypes of blood vessels were found in the mouse dental pulp, which constituted the arterioles-capillaries-venules network. The density of capillaries and venules of molars declined obviously in aged mice. Among the age-dependent changes in the perivascular pulp matrix, the perivascular macrophages remarkably increased, lymphatic capillaries increased, while the nerves and extracellular matrix remained unchanged. Furthermore, the vascular patterns of human formed a complex vascular network. Both mouse and human dental pulps exhibited an inflammaging state. TNF pathway and Rap1 pathway might become promising targets for combating inflammaging and promoting angiogenesis. CONCLUSIONS: Five subtypes of blood vessels were identified within the dental pulp of mice. Notably, the density of capillaries and venules in pulps of aged mice was reduced. Furthermore, partial similarities were observed in the vascular patterns between the dental pulps of humans and mice. RNA-sequencing analysis revealed that both mouse and human dental pulps exhibit indications of an inflammaging state. CLINICAL SIGNIFICANCE: This study may contribute to unraveling potential therapeutic targets in the pulp regeneration and treatment of relevant diseases in the elderly.

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery.

Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers' healing speed or halting early tumor progression.

Drug-Delivery Nanoplatform with Synergistic Regulation of Angiogenesis-Osteogenesis Coupling for Promoting Vascularized Bone Regeneration.

It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the half-life of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis-osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO@ZIF-8. Additionally, due to the sustained release of DFO and Zn2+, DFO@ZIF-8 NPs were able to promote angiogenesis in human umbilical vein endothelial cells (HUVECs) culture and osteogenesis in bone marrow stem cells (BMSCs) in vitro. Furthermore, the DFO@ZIF-8 NPs promoted vascularization by enhancing the expression of type H vessels and a vascular network. The DFO@ZIF-8 NPs promoted bone regeneration in vivo by increasing the expression of OCN and BMP-2. RNA sequencing analysis revealed that the PI3K-AKT-MMP-2/9 and HIF-1α pathways were upregulated by DFO@ZIF-8 NPs in HUVECs, ultimately leading to the formation of new blood vessels. In addition, the mechanism by which DFO@ZIF-8 NPs promoted bone regeneration was potentially related to the synergistic effect of angiogenesis-osteogenesis coupling and Zn2+-mediation of the MAPK pathway. Taken together, DFO@ZIF-8 NPs, which were demonstrated to have low cytotoxicity and excellent coupling of angiogenesis and osteogenesis, represent a promising strategy for the reconstruction of critical-sized bone defects.

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention.

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention.