Fibrin-konjac glucomannan-black phosphorus hydrogel scaffolds loaded with nasal ectodermal mesenchymal stem cells accelerated alveolar bone regeneration.

BACKGROUND: Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels. METHODS: Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration. RESULTS: The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated. CONCLUSIONS: EMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix.

Black phosphorus quantum dot-modified ADSCs as a novel therapeutic for periodontitis bone loss coupling of osteogenesis and osteoimmunomodulation.

Alveolar bone defect repair remains a persistent clinical challenge for periodontitis treatment. The use of peripheral functional seed cells is a hot topic in periodontitis. Herein, we explored the cellular behaviors and osteogenic ability of adipose-derived mesenchymal stem cells (ADSCs) treated with black phosphorus quantum dots (BPQDs). Additionally, macrophage polarization, osteogenic effects and angiogenesis were investigated through the paracrine pathway regulated by BPQD-modified ADSCs. Our results demonstrated that BPQDs showed good biocompatibility with ADSCs and BPQD-modified ADSCs could improve the bone repair in vivo inflammatory microenvironment by regulating osteogenesis and osteoimmunomodulation. The BPQDs increased the osteogenic differentiation of ADSCs via the Wnt/ß-catenin and BMP2/SMAD5/Runx2 signaling pathway. In addition, BPQD-modified ADSCs promoted the osteogenic effect of BMSCs and facilitated the polarization of macrophages from M1 towards M2 phenotype transformation through the paracrine pathway in the periodontitis microenvironment. This strategy provides a novel idea for treatment of alveolar bone defects for periodontitis in the foreseeable future.

A novel approach in biomedical engineering: The use of polyvinyl alcohol hydrogel encapsulating human umbilical cord mesenchymal stem cell-derived exosomes for enhanced osteogenic differentiation and angiogenesis in bone regeneration.

Developing effective methods for alveolar bone defect regeneration is a significant challenge in orthopedics. Exosomes from human umbilical cord mesenchymal stem cells (HUMSC-Exos) have shown potential in bone repair but face limitations due to undefined application methods and mechanisms. To address this, HUMSC-Exos were encapsulated in polyvinyl alcohol (PVA) hydrogel (Exo@PVA) to create a novel material for alveolar bone repair. This combination enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) more effectively than Exos alone. Additionally, Exo@PVA significantly improved alveolar bone regeneration and defect repair in rats. The microRNA-21-5p (miR-21-5p) in Exo@PVA, identified through the GEO database and analyzed via in silico methods, played a crucial role. miR-21-5p promoted BMSC osteogenic differentiation by inhibiting WWP1-mediated KLF5 ubiquitination and enhanced HUVEC angiogenesis by targeting ATP2B4. These findings underscore the potential of an Exo-based approach with PVA hydrogel scaffolds for bone defect repair, operating through the miR-21-5p/WWP1/ATP2B4 signaling axis.

Recent Advances in Scaffolds for Guided Bone Regeneration.

The rehabilitation of alveolar bone defects of moderate to severe size is often challenging. Currently, the therapeutic approaches used include, among others, the guided bone regeneration technique combined with various bone grafts. Although these techniques are widely applied, several limitations and complications have been reported such as morbidity, suboptimal graft/membrane resorption rate, low structural integrity, and dimensional stability. Thus, the development of biomimetic scaffolds with tailor-made characteristics that can modulate cell and tissue interaction may be a promising tool. This article presents a critical consideration in scaffold's design and development while also providing information on various fabrication methods of these nanosystems. Their utilization as delivery systems will also be mentioned.

Polymethylmethacrylate-hydroxyapatite antibacterial and antifungal activity against oral bacteria: An in vitro study.

Objective: Reconstruction of alveolar bone defects resulting from aging, trauma, ablative surgery or pathology, remains a significant clinical challenge. The objective of this study was to investigate the antibacterial and antifungal activities of mixed polymethylmethacrylate-hydroxyapatite (PMMA-HA) against oral microorganisms. Our findings could provide valuable insights into the prospective application of PMMA-HA as a synthetic bone graft material to manage alveolar bone defects via tissue engineering. Methods: HA powder was obtained from the Center for Ceramics in Indonesia and PMMA granules were obtained from HiMedia Laboratories; these were prepared in 20:80, 30:70, and 40:60 ratios. The antibacterial diffusion method was then performed against Staphylococcusaureus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum, while the antifungal diffusion method was used to test against Candida albicans. Standardized protocols were used for microbial culturing and inhibition zones were measured with digital calipers. Statistical analyses included one-way ANOVA and Kruskal-Wallis tests, supplemented by post-hoc Tukey HSD tests. Results: A PMMA-HA scaffold with a 20:80 ratio demonstrated the highest antibacterial activity against S. aureus, A. actinomycetemcomitans, P. gingivalis, and F. nucleatum. This was followed by the 30:70 and 40:60 ratios in terms of antibacterial activity. Statistical significance was achieved with p < 0.05 in comparison to controls. However, none of the PMMA-HA ratios showed antifungal activity against C. albicans. Conclusion: PMMA-HA scaffolds have significant activity against bacteria, but not against fungi.

Preparation and characterization of silk fibroin/bioactive glass composite fiber membrane / 中国组织工程研究

BACKGROUND:In the construction of guided bone regeneration membrane with biological function,a single material cannot meet the clinical needs due to its insufficient function,so the composite of multiple materials has become a trend of tissue repair engineering. OBJECTIVE:To prepare silk fibroin/bioactive glass composite fiber membranes by electrospinning technology,and to characterize the physicochemical properties and biocompatibility in vitro. METHODS:The solution of electrospinning was prepared by dissolving 0.8 g silk fibroin protein in 10 mL hexafluoro-isopropanol alcohol,and the nanofiber membrane of silk fibroin protein was prepared by electrospinning technology(denoted as SF fiber membrane).0.1,0.3,0.5,and 0.8 g of bioactive glass were added to the electrospinning solution,and the silk fibroin/bioactive glass composite fiber membrane was prepared by electrospinning technology(recorded as SF/1BG,SF/3BG,SF/5BG,and SF/8BG fiber membrane in turn).The physicochemical properties and biocompatibility of five groups of fiber membranes were characterized. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results showed that nanofibers of the prepared composite membrane were smooth,continuous and uniform and had no beaded structure.There was no obvious adhesion between the silk fibers,and they all showed random arrangement of disordered porous structures.The fiber diameter of the fiber membrane decreased after the addition of bioactive glass.Fourier infrared spectroscopy and X-ray diffraction detection results showed that the chemical structure of silk fibroin protein and bioactive glass in fiber membrane was stable.The water contact angles of SF,SF/1BG,SF/3BG,SF/5BG,and SF/8BG were 105.02°,72.58°,78.13°,79.35°,and 72.50°,respectively.(2)Bone marrow mesenchymal stem cells were inoculated on five groups of fiber membranes.CCK-8 assay results showed that SF/1BG,SF/3BG,and SF/5BG fiber membranes could promote the proliferation of bone marrow mesenchymal stem cells compared with SF and SF/8BG.Live cell/dead cell staining showed that the cell vitality on the surface of the five groups of fiber membranes was better,and the number and distribution of cells on the surface of SF/5BG fiber membrane were more uniform.Rhodamine phalloidin staining and scanning electron microscopy exhibited that compared with SF fiber membrane,the SF/5BG fiber membrane was more favorable to the adhesion of bone marrow mesenchymal stem cells.Bone marrow mesenchymal stem cells were inoculated on the fiber membrane of the five groups for osteogenic induction differentiation,and the alkaline phosphatase activity of the SF/3BG and SF/5BG groups was higher than that of the other three groups(P＜0.05,P＜0.01,P＜0.001).Alizarin red staining showed that the formation of calcium nodules in fiber membrane increased after the addition of bioactive glass,and the formation of calcium nodules in the SF/5BG group was the most.(3)The results show that silk fibroin/bioactive glass composite fiber membrane has good biosafety and biocompatibility.

Alveolar bone remodelling and stability of mandibular incisors in adult patients after orthodontic treatment with premolar extractions: A prospective follow-up study.

OBJECTIVE: To evaluate alveolar bone remodelling and stability of mandibular incisors in adult orthodontic extraction patients. MATERIALS AND METHODS: Cone-beam computed tomography images of 25 adult patients undergoing extraction were collected before orthodontic treatment (T1), after orthodontic treatment (T2), and after at least 1 year of retention (T3). The labial and lingual alveolar bone heights (ABH), thickness (ABT), and tooth movement of the mandibular incisors were measured during the retraction (T2-T1) and retention (T3-T2) periods. According to the tooth movement during the retention period, the mandibular incisors were further divided into stable and unstable groups, and the correlation between L1-BMe and stability was evaluated. RESULTS: The labial and lingual ABHs significantly increased after orthodontic treatment and decreased during the retention period. The lingual ABH was 7.36 ± 2.27 mm at T2 and 5.37 ± 1.98 mm at T3, indicating a great bone remodelling capacity. The labial ABT exhibited a significant increase during orthodontic treatment and a slight decrease during the retention period, while the lingual ABT showed an opposite trend. During the retention period, the root apex moved labially into the alveolar bone housing. L1-BMe significantly increased during orthodontic treatment and decreased during the retention period. Compared to the stable group, lingual ABH and L1-BMe at T2 was significantly higher, and lingual ABT was smaller in the unstable group. CONCLUSION: Post-treatment lingual alveolar bone defects of the mandibular incisors could recover to some extent during the retention period. There was a negative correlation between post-treatment L1-BMe and mandibular incisor stability.

Long-term bone remodeling of maxillary anterior teeth with post-treatment alveolar bone defect in adult patients with maxillary protrusion: a prospective follow-up study.

BACKGROUND: Alveolar bone defects, particularly palatal bone dehiscence (PBD) and labial bone fenestration (LBF), occur frequently as a result of retraction of the maxillary anterior teeth. The study aims to explore the long-term bone remodeling of maxillary anterior teeth in adult patients with post-orthodontic treatment PBD and LBF. MATERIALS AND METHODS: The study includes 24 adult patients with maxillary protrusion (8 males, 16 females) who were treated with extraction of four first premolars and had alveolar bone defects (PBD or LBF) in maxillary anterior teeth following orthodontic treatment. Cone-beam computed tomography imaging measurements were obtained before (T1), after (T2) orthodontic treatment, and after at least 1-year removable thermoplastic retainer retention (T3). The maxillary anterior teeth with PBD or LBF at T2 were divided into the PBD or LBF groups, respectively. The labial and palatal alveolar bone height (ABH), alveolar bone thickness (ABT), and movement of maxillary anterior teeth were measured during retraction (T2-T1) and retention (T3-T2) periods. RESULTS: The incidence of PBD and LBF in maxillary anterior teeth significantly increased after orthodontic treatment and decreased during the retention period. In the PBD group, the palatal ABH of all maxillary anterior teeth significantly increased from T1 to T2 but decreased from T2 to T3. The ABT of the maxillary central incisor and canine significantly increased on the palatal side and decreased on the labial side during the retention period. In the LBF group, the labial ABT of the maxillary central incisor at the apical level showed a significant decrease from T1 to T2, followed by an increase from T2 to T3. In both groups, the maxillary central incisor showed significant labial movement, with a relative intrusion during the retention period. CONCLUSION: For adult patients with maxillary protrusion, the alveolar bone defect of maxillary anterior teeth caused by orthodontic retraction significantly improved during the retention period, indicating good long-term bone remodeling. Our findings suggest that a combination of spontaneous reorientation of maxillary anterior teeth and bone remodeling contributed to alveolar bone covering in these patients.

Human alveolar bone-derived mesenchymal stem cell cultivation on a 3D-printed PDLLA scaffold for bone formation.

This study aimed to assess effects of 3-dimensionally (3D) printed poly-d,l-lactin (PDLLA) on human alveolar bone-derived mesenchymal stem cell (h-ABMSC) osteogenic proliferation and differentiation. Human ABMSCs were cultured and identified using flow cytometry and morphological analysis. Control and PDLLA experimental groups were assessed using a Cell Counting Kit-8 (CCK-8) to detect cellular cytotoxicity and proliferative activity. Real-time quantitative polymerase chain reaction was used to determine expression levels of osteogenesis genes including alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), and osteocalcin (OCN). The results showed that h-ABMSCs were successfully cultured and revealed by microscopic observation. Human ABMSCs were spindle-shaped, with clustered and fish-like primary cells. Cell surface markers were negative for CD34 and positive for CD44 and CD90. PDLLA had no cytotoxicity. Human ABMSCs proliferated normally, and osteogenic differentiation of the cells was observed on the surface of PDLLA. Cellular proliferative activity and expression levels of osteogenesis-related genes of PDLLA and control groups showed no significant difference, including ALP, Runx-2, OPN, and OCN. These results suggest that 3D-printed PDLLA has good cell compatibility and biological activity.

Endogenous Regeneration of Alveolar Bone by Decellularized Tooth Matrix.

The efficiency of bone tissue regeneration by decellularized tooth matrix, demineralized tooth matrix, and commercial xenograft Bio-Oss Spongiosa was compared on the model of a critical-size circular defect in the alveolar bone of the upper jaw of adult Wistar rats. The defect healing dynamics was assessed using histological, histomorphometrical, and immunohistochemical methods on days 30 and 60. In contrast to demineralized matrix and commercial xenograft, decellularized matrix induces the formation of the new bone tissue by day 60. Decellularized matrix can be considered as a biomaterial for cell-free tissue engineering for alveolar bone restoration in dentistry and maxillofacial surgery.

Injectable platelet-rich fibrin polymerized with hydroxyapatite bone graft for the treatment of three-wall intrabony defects: A randomized control clinical trial.

Background: The study was aimed to compare and evaluate the clinical and radiographic outcomes of injectable platelet-rich fibrin (i-PRF) polymerized with hydroxyapatite (HA) bone graft and HA bone graft alone for treating three-wall intrabony defects (IBDs). Materials and Methods: The trial was planned as a randomized, prospective clinico-radiographic study with inclusion of 34 three-wall IBDs in patients with stage III periodontitis. IBDs were assigned randomly to one of the groups, i.e., Group I - experimental (i-PRF + HA) and Group II - control (HA alone). At baseline and 6 and 9-month intervals, both the clinical and radiographic measurements were taken and baseline and 9-month data were tabulated and imported into SPSS 22 software. Student unpaired and paired t- tests were used to find significant differences (p<0.05). Results: Both the groups showed substantial changes in all clinical and radiographic measures on comparison from baseline values. On intergroup comparison, the i-PRF + HA group reported significantly higher original defect resolution and original defect fill as compared to the HA group. Conclusion: i-PRF polymerized with HA graft has shown better results as compared to HA graft alone in three-wall IBDs and therefore can be used as a better possible alternative for the treatment of three-wall IBDs.

Application of three-dimensional printing individualized titanium mesh in alveolar bone defects with different Terheyden classifications: A retrospective case series study.

OBJECTIVE: To present the results of guided bone regeneration (GBR) with three-dimensional printing individualized titanium mesh (3D-PITM) applied to alveolar bone defects with different Terheyden classifications and the factors affecting the osteogenic outcome. MATERIALS AND METHODS: Fifty-nine patients, presenting with 61 defect sites, were enrolled between 2018 and 2021. GBR+3D-PITM was obtained with simultaneous or second stage implant placement. The complication rate, the success rate of the bone grafting procedure and the survival rate of the implant were documented. Bone gain, thickness of pseudo-periosteum and peri-implant marginal bone loss (MBL) were measured through digital methods by imaging data (CBCT and X-ray). RESULTS: Out of 61 sites, 20 were exposed (exposure rate: 32.8%). The width, height, and volume bone gain at P3 (mesh removal) were 5.22 ± 3.19 mm, 5.01 ± 2.83 mm, and 588.91 ± 361.23 mm3 , respectively. From P2 (3D-PITM+GBR) to P3 , changes in bone gain were not statistically different in the different Terheyden classifications, the occurrence of exposure (p < .001 for all dimensions) and the different type of pseudo-periosteum (p = .030 for width and p = .002 for height) were significantly correlated with the reduction of bone gain. Terheyden classification of the defect sites was significantly associated with the occurrence of exposure (p = .014) and types of the pseudo-periosteum (p = .015). CONCLUSION: The 3D-PITM can be used in alveolar bone defects with different Terheyden classification, but cases with severe vertical bone defects have a greater chance of the 3D-PITM exposure and the exposure can affect the outcome of bone augmentation.

PF127 Hydrogel-Based Delivery of Exosomal CTNNB1 from Mesenchymal Stem Cells Induces Osteogenic Differentiation during the Repair of Alveolar Bone Defects.

Pluronic F127 (PF127) hydrogel has been highlighted as a promising biomaterial for bone regeneration, but the specific molecular mechanism remains largely unknown. Herein, we addressed this issue in a temperature-responsive PF127 hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exos) (PF127 hydrogel@BMSC-Exos) during alveolar bone regeneration. Genes enriched in BMSC-Exos and upregulated during the osteogenic differentiation of BMSCs and their downstream regulators were predicted by bioinformatics analyses. CTNNB1 was predicted to be the key gene of BMSC-Exos in the osteogenic differentiation of BMSCs, during which miR-146a-5p, IRAK1, and TRAF6 might be the downstream factors. Osteogenic differentiation was induced in BMSCs, in which ectopic expression of CTNNB1 was introduced and from which Exos were isolated. The CTNNB1-enriched PF127 hydrogel@BMSC-Exos were constructed and implanted into in vivo rat models of alveolar bone defects. In vitro experiment data showed that PF127 hydrogel@BMSC-Exos efficiently delivered CTNNB1 to BMSCs, which subsequently promoted the osteogenic differentiation of BMSCs, as evidenced by enhanced ALP staining intensity and activity, extracellular matrix mineralization (p < 0.05), and upregulated RUNX2 and OCN expression (p < 0.05). Functional experiments were conducted to examine the relationships among CTNNB1, microRNA (miR)-146a-5p, and IRAK1 and TRAF6. Mechanistically, CTNNB1 activated miR-146a-5p transcription to downregulate IRAK1 and TRAF6 (p < 0.05), which induced the osteogenic differentiation of BMSCs and facilitated alveolar bone regeneration in rats (increased new bone formation and elevated BV/TV ratio and BMD, all with p < 0.05). Collectively, CTNNB1-containing PF127 hydrogel@BMSC-Exos promote the osteogenic differentiation of BMSCs by regulating the miR-146a-5p/IRAK1/TRAF6 axis, thus inducing the repair of alveolar bone defects in rats.

Development and validation of intraoral periapical radiography-based machine learning model for periodontal defect diagnosis.

Radiographic determination of the bone level is useful in the diagnosis and determination of the severity of the periodontal disease. Various two- and three-dimensional imaging modalities offer choices for imaging pathologic processes that affect the periodontium. In recent years, innovative computer techniques, especially artificial intelligence (AI), have begun to be used in many areas of dentistry and are helping increase treatment and diagnostic performance. This study was aimed at developing a machine-learning (ML) model and assessing the extent to which it was capable of classifying periodontal defects on 2D periapical images. Eighty-seven periapical images were examined as part of this research. The existence or absence of periodontal defects in the aforementioned images were evaluated by a human observer. The evaluations were subsequently repeated using a radiomics platform. A comparison was made of all data acquired through human observation and ML techniques by SVM analysis. According to the study findings the ability of human observers and the ML model to detect periodontal defects was significantly different in comparison to the gold standard. However, ML and human observers performed similarly for the detection of periodontal defects without a significant difference. This study reveals that the prediction of periodontal defects can be achieved by combining particular radiomic features with image variables. The proposed machine leaning model can be utilized for supporting clinical practitioners and eventually substitute evaluations conducted by human observers while enhancing future levels of performance.

Research progress on "sandwich" osteotomy to increase alveolar bone / 口腔疾病防治

@#Lack of alveolar bone height is a major challenge for dental implants. In recent years, the use of "sandwich" osteotomy to increase alveolar bone height has become a topic of discussion within the research community. In theory, "sandwich" osteotomy is a U-shaped osteotomy in the bone defect area, to preserve the blood supply of the mucoperiosteal on the lingual side and to create an artificial "four-wall bone bag" to build a favorable space for osteogenesis and to increase the height of the alveolar bone. Histological studies have shown that the osteogenesis speed of "sandwich" osteotomy is fast, and the bone is good. Sandwich osteotomy is suitable for buccal-lingual alveolar bone height defects less than 50% of the implant length or for unilateral defects more than 50% of the implant length. In the operation of "sandwich" osteotomy, the horizonal incision should be 10-12 mm below the crest of the buccal alveolar ridge. The design of the osteotomy line should ensure the height of the osteotomy block and that the mandibular canal does not sustain damage and that it fits the shape of the bone defect. There was no significant difference in the osteogenic effect of different types of bone graft materials used for "sandwich" osteotomy. The osteotomy block was rigorously fixed by a titanium plate, titanium nail, implant and other materials, and finally, the intraoperative area was tensioned and sutured. The effect of bone augmentation was evaluated and compared with other bone augmentation techniques; the evaluation showed that sandwich osteotomy was better for moderate vertical bone defects. This technique is highly sensitive and postoperative transient sensory loss is common. With advances in technology, the application of digital technology and ultrasonic bone knives, the risk of complications is greatly reduced and advances in digital osteotomy will promote apply of "sandwich" osteotomy, which will become a popularized technique for clinical alveolar bone augmentation.

Pro-angiogenic photo-crosslinked silk fibroin hydrogel: a potential candidate for repairing alveolar bone defects

Abstract Objective: This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair. Methodology: Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also stained to evaluate inflammatory responses after implantation. Results: GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses. Conclusion: This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.

The Experimental Study of Periodontal Ligament Stem Cells Derived Exosomes with Hydrogel Accelerating Bone Regeneration on Alveolar Bone Defect.

INTRODUCTION: this study was conducted to investigate the osteogenic ability of periodontal ligament stem cells (PDLSCs) derived exosomes (PDLSCs-Exos) and the effect of PDLSCs-Exos with hydrogel on alveolar bone defect repairment in the rat. METHODS: the PDLSCs were obtained through primary cell culture, and PDLSCs-Exos were purified by the ultracentrifugation method. The CCK-8 kit and ALP staining were used to explore the effect of PDLSCs-Exos on promoting the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo, the alveolar bone defect models were made mesial to the bilateral maxillary first molars of rats. MicroCT, HE staining, and Masson staining were used to analyze the new bone at the bone defect of rats. RESULTS: the periodontal ligament stem cells and the periodontal ligament stem cells derived exosomes were successfully extracted. The results of the CCK-8 kit and ALP staining showed PDLSCs-Exos significantly promoted the proliferation osteogenic differentiation of BMSCs. In vivo experiment results revealed that compared with the control group and the hydrogel group, the rats in the hydrogel with exosomes group showed more new bone formation in alveolar bone defects. CONCLUSION: Periodontal ligament stem cells and exosomes derived from periodontal ligament stem cells were successfully extracted. The results demonstrated that the hydrogel successfully delivered periodontal ligament stem cells derived exosomes for repairing alveolar bone defects in rats in vivo at the initial stage.

Periosteum coverage versus collagen-membrane coverage in periodontally accelerated osteogenic orthodontics: a randomized controlled clinical trial in Class II and Class III malocclusions.

BACKGROUND: Periodontal accelerated osteogenic orthodontics (PAOO) is a widely-used clinical procedure that combines selective alveolar corticotomy, particulate bone grafting, and the application of orthodontic forces. Different modifications of PAOO such as collagen-membrane coverage can better benefit patients from preventing displacement of grafts. Due to its stability, collagen-membrane coverage gradually gained popularity and became a widely-used procedure in traditional PAOO technique. OBJECTIVES: To quantitatively investigate the radiographic changes of alveolar bone, periodontal soft tissue changes of the mandibular anterior teeth and postoperative complications in periosteum-covered techniques compared with traditional surgical technique in PAOO. METHODS: Orthodontic camouflage for dental Class II or decompensation for skeletal Class III malocclusions were included; Patients with bone defects on the buccal aspects of the anterior mandible regions confirmed by clinical and radiographic examination were randomly divided into the periosteum coverage group or traditional technique group for PAOO. Cone-beam computerized tomography (CBCT) scans were obtained before treatment (T0) and 1 week (T1) and 12 months (T2) after operation. The primary outcome variable was the vertical alveolar bone level (VBL), the secondary evaluation parameters included labial horizontal bone thickness at the midpoint of the middle third (MHBT) or apical third (AHBT) to the limit of the labial cortical surface during a 12-month follow-up. Postoperative sequelae were evaluated after 2 days and 7 days in both the groups. Periodontal parameters were analyzed at T0 and T2. RESULTS: Thirty-six adult subjects were eligible and recruited in the present study. Although experimental group exhibited more severe infection, no significant differences of the postoperative symptoms or periodontal parameters was found between the 2 groups (P > 0.05). All patients were examined respectively using CBCT at baseline (T0), postoperative 1 week (T1) and 12 months (T2). Both alveolar bone height and width increased from T0 to T1 (P < 0.001) and then reduced from T1 to T2 (P < 0.001) in both groups. However, significant bone augmentation was achieved in each group from T0 to T2 (P < 0.001). Furthermore, the vertical alveolar bone augmentation in the experimental group increased significantly than that in the traditional surgery (P < 0.05). CONCLUSIONS: Compared with traditional PAOO surgery, the periosteum-covered technique provides superior graft stabilization and satisfactory vertical bone augmentation in the labial mandibular anterior area.

Biomechanical Effects of 3D-Printed Bioceramic Scaffolds With Porous Gradient Structures on the Regeneration of Alveolar Bone Defect: A Comprehensive Study.

In the repair of alveolar bone defect, the microstructure of bone graft scaffolds is pivotal for their biological and biomechanical properties. However, it is currently controversial whether gradient structures perform better in biology and biomechanics than homogeneous structures when considering microstructural design. In this research, bioactive ceramic scaffolds with different porous gradient structures were designed and fabricated by 3D printing technology. Compression test, finite element analysis (FEA) revealed statistically significant differences in the biomechanical properties of three types of scaffolds. The mechanical properties of scaffolds approached the natural cancellous bone, and scaffolds with pore size decreased from the center to the perimeter (GII) had superior mechanical properties among the three groups. While in the simulation of Computational Fluid Dynamics (CFD), scaffolds with pore size increased from the center to the perimeter (GI) possessed the best permeability and largest flow velocity. Scaffolds were cultured in vitro with rBMSC or implanted in vivo for 4 or 8 weeks. Porous ceramics showed excellent biocompatibility. Results of in vivo were analysed by using micro-CT, concentric rings and VG staining. The GI was superior to the other groups with respect to osteogenicity. The Un (uniformed pore size) was slightly inferior to the GII. The concentric rings analysis demonstrated that the new bone in the GI was distributed in the periphery of defect area, whereas the GII was distributed in the center region. This study offers basic strategies and concepts for future design and development of scaffolds for the clinical restoration of alveolar bone defect.

Sphingosine-1-phosphate receptor 2 agonist induces bone formation in rat apicoectomy and alveolar bone defect model.

Background/purpose: Sphingosine-1-phosphate (S1P) is a lipid mediator that exerts its physiological functions in vivo through receptors. In the bone, S1P induces osteoblast differentiation. Here, we investigated the effects of S1P receptor agonists on the expression of osteoblast differentiation markers locally in the bone. Then, a rat apicoectomy and alveolar bone defect model was established to extend S1P applications to endodontics, and the effect of local administration of S1P receptor agonist on postoperative bone formation was examined. Materials and methods: Sphingosine-1-phosphate receptor (S1PR) 1/S1PR3 agonists, S1PR2 agonists, and their signal-related agents were intraperitoneally administered to mice. Using the mRNA collected from the tibial bone, the expression of osteoblast differentiation markers was evaluated by real-time reverse-transcriptase quantitative polymerase chain reaction. An apicoectomy and alveolar bone defect model was established on the mesial root of the rat mandibular first molar. Bone formation parameters were measured by micro-computed tomography analysis 3 weeks after the procedure. Results: Intraperitoneal administration of S1PR2 agonist significantly increased the mRNA expression of osteoblast differentiation markers, including alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin, in the local tibial bone of mice. The S1PR2/Rho-associated coiled-coil forming kinase (ROCK) signaling was thought to be involved in the upregulated mRNA expression of ALP, OPN, and BSP. In the rat apical defects, bone formation parameters significantly increased following local administration of S1PR2 agonist. Conclusion: In the rat apicoectomy and alveolar bone defect model, therapeutic agents targeting S1PR2 agonist are effective against osteogenesis.