Modulating cell stiffness for improved vascularization: leveraging the MIL-53(fe) for improved interaction of titanium implant and endothelial cell.

Vascularization plays a significant role in promoting the expedited process of bone regeneration while also enhancing the stability and viability of artificial bone implants. Although titanium alloy scaffolds were designed to mimic the porous structure of human bone tissues to facilitate vascularization in bone repair, their biological inertness restricted their broader utilization. The unique attribute of Metal-organic framework (MOF) MIL-53(Fe), known as "breathing", can facilitate the efficient adsorption of extracellular matrix proteins and thus provide the possibility for efficient interaction between scaffolds and cell adhesion molecules, which helps improve the bioactivity of the titanium alloy scaffolds. In this study, MIL-53(Fe) was synthesized in situ on the scaffold after hydrothermal treatment. The MIL-53(Fe) endowed the scaffold with superior protein absorption ability and preferable biocompatibility. The scaffolds have been shown to possess favorable osteogenesis and angiogenesis inducibility. It was indicated that MIL-53(Fe) modulated the mechanotransduction process of endothelial cells and induced increased cell stiffness by promoting the adsorption of adhesion-mediating extracellular matrix proteins to the scaffold, such as laminin, fibronectin, and perlecan et al., which contributed to the activation of the endothelial tip cell phenotype at sprouting angiogenesis. Therefore, this study effectively leveraged the intrinsic "breathing" properties of MIL-53 (Fe) to enhance the interaction between titanium alloy scaffolds and vascular endothelial cells, thereby facilitating the vascularization inducibility of the scaffold, particularly during the sprouting angiogenesis phase. This study indicates that MIL-53(Fe) coating represents a promising strategy to facilitate accelerated and sufficient vascularization and uncovers the scaffold-vessel interaction from a biomechanical perspective.

Synergistic effect of hierarchical topographic structure on 3D-printed Titanium scaffold for enhanced coupling of osteogenesis and angiogenesis.

The significance of the osteogenesis-angiogenesis relationship in the healing process of bone defects has been increasingly emphasized in recent academic research. Surface topography plays a crucial role in guiding cellular behaviors. Metal-organic framework (MOF) is an innovative biomaterial with nanoscale structural and topological features, enabling the modulation of scaffold physicochemical properties. This study involved the loading of varying quantities of UiO-66 nanocrystals onto alkali-heat treated 3D-printed titanium scaffolds, resulting in the formation of hierarchical micro/nano topography named UiO-66/AHTs. The physicochemical properties of these scaffolds were subsequently characterized. Furthermore, the impact of these scaffolds on the osteogenic potential of BMSCs, the angiogenic potential of HUVECs, and their intercellular communication were investigated. The findings of this study indicated that 1/2UiO-66/AHT outperformed other groups in terms of osteogenic and angiogenic induction, as well as in promoting intercellular crosstalk by enhancing paracrine effects. These results suggest a promising biomimetic hierarchical topography design that facilitates the coupling of osteogenesis and angiogenesis.

Improving osteoinduction and osteogenesis of Ti6Al4V alloy porous scaffold by regulating the pore structure.

Titanium alloy scaffolds with a porous structure have attracted much attention in bone defect repair. However, which pore structure is more beneficial to bone defect repair is controversial. In the present research, the Ti6Al4V alloy porous scaffolds with gradient pore sizes were designed and fabricated. The microstructure characterization, tests of mechanical properties, and in vitro and in vivo experiments have been performed to systematically evaluate the effect of pore size on osteoinduction and osteogenesis. The results revealed that the contact angle with water, compressive strength, and elastic modulus of the Ti6Al4V alloy porous scaffolds decreased gradually with the increase of pore size. However, there were obvious drops when the pore size of the porous scaffold was around 600 µm. As the pore size increased, the proliferation and integrin ß1 of RAW 264.7 macrophages seeded on Ti6Al4V alloy porous scaffolds increased at first, reaching a maximum value at a pore size of around 600 µm, and then decreased subsequently. The proliferation, integrin ß1, and osteogenic gene-related expressions of Bone marrow mesenchymal stem cells (BMSCs) seeded on Ti6Al4V alloy porous scaffolds with different pore sizes all exhibited similar variations which rose with increased pore size firstly, obtaining the maximum value at pore size about 600 µm, and then declined. The in vivo experiments confirmed the in vitro results, and the Ti6Al4V alloy porous scaffold with a pore size of 600 µm possessed the better capability to induce new bone formation. Therefore, for the design of Ti6Al4V alloy with a regular porous scaffold, the surface morphology, porosity, strength, and elastic modulus should be considered systematically, which would determine the capability of osteoinduction and osteogenesis.

Concentration-Dependent Cellular Uptake of Graphene Oxide Quantum Dots Promotes the Odontoblastic Differentiation of Dental Pulp Cells via the AMPK/mTOR Pathway.

As zero-dimension nanoparticles, graphene oxide quantum dots (GOQDs) have broad potential for regulating cell proliferation and differentiation. However, such regulation of dental pulp cells (DPSCs) with different concentrations of GOQDs is insufficiently investigated, especially on the molecular mechanism. The purpose of this study was to explore the effect and molecular mechanism of GOQDs on the odontoblastic differentiation of DPSCs and to provide a theoretical basis for the repair of pulp vitality by pulp capping. CCK-8, immunofluorescence staining, alkaline phosphatase activity assay and staining, alizarin red staining, qRT-PCR, and western blotting were used to detect the proliferation and odontoblastic differentiation of DPSC coculturing with different concentrations of GOQDs. The results indicate that the cellular uptake of low concentration of GOQDs (0.1, 1, and 10 µg/mL) could promote the proliferation and odontoblastic differentiation of DPCSs. Compared with other concentration groups, 1 µg/mL GOQDs show better ability in such promotion. In addition, with the activation of the AMPK signaling pathway, the mTOR signaling pathway was inhibited in DPSCs after coculturing with GOQDs, which indicates that low concentrations of GOQDs could regulate the odontoblastic differentiation of DPSCs by the AMPK/mTOR signaling pathway.

Two Novel Mutations in Ectodysplasin-A Identified in Syndromic Tooth Agenesis.

OBJECTIVE: To discover novel ectodysplasin-A (EDA) and wingless-type MMTV integration site family, member 10A (WNT10A) mutations in tooth agenesis (TA) patients. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Guanghua School of Stomatology, Guangzhou, China, from March 2018 to August 2020. METHODOLOGY: EDA and WNT10A were analysed in eleven TA families by PCR and Sanger sequencing. Bioinformatics and structure modelling analyses were performed after identifying different variants, to predict the resulting conformational alterations in WNT10A and EDA. RESULTS:  Two novel mutations (c.796C>A (p.L266I), c.769G>A (p.G257R)) in EDA and two reported mutations (c.637G>A (p.G213S), c.511C>T (p.R171C))in WNT 10A were detected. Combined with the 3D structural analysis, we discovered a correlation between alterations in hydrogen bond formation and the observed phenotypes, potentially affecting protein binding. CONCLUSIONS: The mutations were predicted to be pathogenic through bioinformatics analyses. In addition, by identifying novel mutations, our knowledge regarding the TA spectrum and tooth development was considerably expanded. KEY WORDS:  Anodontia, EDA, WNT 10A, Whole exome sequencing, Odontogenesis.

Effects of Low-Concentration Graphene Oxide Quantum Dots on Improving the Proliferation and Differentiation Ability of Bone Marrow Mesenchymal Stem Cells through the Wnt/ß-Catenin Signaling Pathway.

Graphene oxide quantum dots (GOQDs) are considered to be a new method for regulating the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). However, there are few reports on such regulation with different concentrations of GOQDs, and the molecular mechanism has not been fully elucidated. The purposes of this study were, first, to explore the effects of GOQDs on the proliferation and differentiation of BMSCs in vitro and in vivo, and, second, to provide a theoretical basis for the repair of bone defects. Live/Dead staining, EdU staining, immunofluorescence staining, alkaline phosphatase (ALP), western blotting, and qT-PCR were used for detecting the proliferation and differentiation of BMSCs after coculture with GOQDs of different concentrations. Hematoxylin and eosin (HE) staining and Van Gieson (VG) staining were used to detect new bone regeneration in vivo. The results showed that low-concentration GOQDs (0.1 and 1 µg/mL) promoted the proliferation and differentiation of BMSCs. Compared with the 1 µg/mL GOQD group, the 0.1 µg/mL GOQD group had better ability to promote the proliferation and differentiation of BMSCs. HE and VG staining results showed the greatest proportion of new bone area on sandblasted, large-grit, and acid-etched (SLA)/GOQD scaffolds. Furthermore, the ratio of active ß-catenin and the phosphorylation level of GSK-3ß (p-GSK-3ß) increased after BMSCs treatment with 0.1 µg/mL GOQDs. Low concentrations of GOQDs improved the osteogenic differentiation ability of BMSCs by activating the Wnt/ß-catenin signaling pathway.

Large-pore-size Ti6Al4V scaffolds with different pore structures for vascularized bone regeneration.

Porous Ti6Al4V scaffolds are characterized by high porosity, low elastic modulus, and good osteogenesis and vascularization, which are expected to facilitate the repair of large-scale bone defects in future clinical applications. Ti6Al4V scaffolds are divided into regular and irregular structures according to the pore structure, but the pore structure more capable of promoting bone regeneration and angiogenesis has not yet been reported. The purpose of this study was to explore the optimal pore structure and pore size of the Ti6Al4V porous scaffold for the repair of large-area bone defects and the promotion of vascularization in the early stage of osteogenesis. 7 groups of porous Ti6Al4V scaffolds, named NP, R8, R9, R10, P8, P9 and P10, were fabricated by Electron-beam-melting (EBM). Live/dead staining, immunofluorescence staining, SEM, CCK8, ALP, and PCR were used to detect the adhesion, proliferation, and differentiation of BMSCs on different groups of scaffolds. Hematoxylin-eosin (HE) staining and Van Gieson (VG) staining were used to detect bone regeneration and angiogenesis in vivo. The research results showed that as the pore size of the scaffold increased, the surface area and volume of the scaffold gradually decreased, and cell proliferation ability and cell viability gradually increased. The ability of cells to vascularize on scaffolds with irregular pore sizes was stronger than that on scaffolds with regular pore sizes. Micro-CT 3D reconstruction images showed that bone regeneration was obvious and new blood vessels were thick on the P10 scaffold. HE and VG staining showed that the proportion of bone area on the scaffolds with irregular pores was higher than that on scaffolds with regular pores. P10 had better mechanical properties and were more conducive to bone tissue ingrowth and blood vessel formation, thereby facilitating the repair of large-area bone defects.

Evaluation of factors affecting alveolar ridge height and facial bone thickness in Chinese maxillary central incisors by cone beam CT.

BACKGROUND/PURPOSE: In the immediate implantation of maxillary central incisors, the height of the alveolar bone is lost, and there is often a risk of bone fracture due to the thin buccal bone wall (BBW). The purpose of this study was to assess the effects of smoking, age, and root position in the alveolar bone on the BBW and the distance between the cemento-enamel junction (CEJ) and the facial bone crest (FBC) of Chinese maxillary central incisors. MATERIALS AND METHODS: The patients were divided by smoking, gender, age, and root sagittal position in the alveolar bone. BBW thickness was measured at the following sites: the 4 mm apical to the CEJ, the middle of the root, and the apex. The distance from the CEJ to the FBC was also evaluated. RESULTS: Cone beam CT (CBCT) data for the maxillary central incisors of 645 patients (323 males and 322 females) were selected and analyzed. The CEJ-FBC distance in patients who smoked (2.79 ±â€¯0.78 mm) was significantly greater than that of non-smokers (2.54 ±â€¯0.69 mm). The BBW in subtype III (0.74 ±â€¯0.43 mm, 0.81 ±â€¯0.36 mm) was thinner than that in subtypes I and II at 4 mm apical to the CEJ and in the middle of the root, with a statistically significant difference (p < 0.05). CONCLUSION: In most Chinese people, smoking, gender, age, and the position of the root in alveolar bone are all important factors that must be considered before immediate implantation is undertaken.

Effect of Pore Size on the Physicochemical Properties and Osteogenesis of Ti6Al4V Porous Scaffolds with Bionic Structure.

Ti6Al4V is widely used in implants in the fields of orthopedics and dentistry due to its high compressive strength and good biocompatibility. Nevertheless, Ti6Al4V has a certain degree of biological inertness and the elastic modulus of Ti6Al4V is much higher than the cortex and trabecular bone. In this study, we designed and printed a new type of pore size Ti6Al4V with like-trabecular structure scaffold (the pore size is 800/900/1000 µm, named P8/P9/P10, respectively) with electron beam melting (EBM). Its elastic modulus, compressive strength, and other physical and chemical properties, as well as cell adhesion, proliferation, and differentiation ability and in vitro biological properties were studied. The physical and chemical performance test results showed that as the pore size increased, the surface wettability increased and the elastic modulus decreased. As the pore size increased, F-actin and alkaline phosphatase (ALP) increased significantly, and osteogenesis-related genes including BMP2, OCN, RUNX2, and ALP were upregulated significantly. The reason may be that the components on the Ti6Al4V pore size may have an influence on intracellular signal conversion and then change the mode of cell proliferation and diffusion. In summary, the like-trabecular porous structure can effectively reduce the elastic modulus of metal materials, thereby avoiding stress concentration and promoting the adhesion and proliferation of osteoblasts. Porous materials with larger pores are more conducive to the proliferation and differentiation of osteoblasts. The irregular porous Ti6Al4V scaffold prepared by the EBM technology has good mechanical properties and the potential to promote adhesion, proliferation, and differentiation of osteoblasts, and has the possibility of application in the field of implantation.

Comparative analysis of the stress distribution in five anatomical types of maxillary central incisor.

BACKGROUND: The maxillary central incisor is one of the most important anatomical indicators in esthetics, and stress distribution may vary among its five anatomical views (labial, palatal, mesial, distal, and incisal). OBJECTIVE: To compare stress distribution among the five anatomical views of the maxillary central incisor under loading force at five angles and to observe and analyze the stress distribution in the dentin and periodontal ligament. METHODS: We established three-dimensional finite element models of the five different views, which simulated the bite force with a static load force at 0∘, 30∘, 45∘, 60∘, and 90∘. The stress and displacement values for the cementoenamel junction (CEJ)-apical labial, palatal, mesial, and distal and the equivalent stress values on the periodontal ligament of the maxillary central incisor were calculated. RESULTS: As the angle increased, the equivalent stress on the periodontal ligament, overall tooth displacement, equivalent stress, and displacement over the four views increased. The peaks of equivalent stress over the four views appeared within 0.8-17 mm below the CEJ, although all equivalent stress values decreased while approaching the peak. Within 1-19 mm below the CEJ, the equivalent stress over the M1 and P1 views of the maxillary central incisor decreased substantially. CONCLUSION: The peaks of the equivalent stress over the M1 and P1 views of the maxillary central incisor and their stress distribution were lower than those of the other three types. Our findings provided theoretical data on the biomechanics of this esthetically important tooth, which may be useful during implantation of missing maxillary central incisors.

Classification of the Root Position of the Maxillary Central Incisors and its Clinical Significance in Immediate Implant Placement.

PURPOSE: The aim was to classify the relationship of the sagittal root positions of the maxillary central incisor to alveolar bone using cone beam computed tomography (CBCT). METHODS: CBCT images of 934 maxillary central incisors were retrospectively reviewed included 542 men and 392 women. The sagittal root position in the alveolar bone was classified as buccal, middle, or palatal. The sagittal buccal type was further classified into 3 subtypes: I, II, and III. RESULTS: The root position type was buccal in 95.4% of the 934 incisors, middle in 4.4%, and palatal in 0.2%. In the buccal type, 47.5%, 44.2%, and 8.3% were subtypes I, II, and III, respectively. There was no significant difference in the major and subtypes of root position between the male and female subjects (both P > 0.05). CONCLUSIONS: In Chinese adults, the predominant type of sagittal root position of the maxillary central incisor is buccal. This classification system is useful in planning the implant site for immediate placement in the maxillary esthetic zone.