A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway.

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Effect of quercetin on chondrocyte phenotype and extracellular matrix expression.

Due to the poor repair ability of cartilage tissue, regenerative medicine still faces great challenges in the repair of large articular cartilage defects. Quercetin is widely applied as a traditional Chinese medicine in tissue regeneration including liver, bone and skin tissues. However, the evidence for its effects and internal mechanisms for cartilage regeneration are limited. In the present study, the effects of quercetin on chondrocyte function were systematically evaluated by CCK8 assay, PCR assay, cartilaginous matrix staining assays, immunofluorescence assay, and western blotting. The results showed that quercetin significantly up-regulated the expression of chondrogenesis genes and stimulated the secretion of GAG (glycosaminoglycan) through activating the ERK, P38 and AKT signalling pathways in a dose-dependent manner. Furthermore, in vivo experiments revealed that quercetin-loaded silk protein scaffolds dramatically stimulated the formation of new cartilage-like tissue with higher histological scores in rat femoral cartilage defects. These data suggest that quercetin can effectively stimulate chondrogenesis in vitro and in vivo, demonstrating the potential application of quercetin in the regeneration of cartilage defects.

Varisized 3D-Printed Lunate for Kienböck's Disease in Different Stages: Preliminary Results.

OBJECTIVE: To evaluate the feasibility of arthroplasty with varisized three-dimensional(3D) printing lunate prosthesis for the treatment of advanced Kienböck's disease (KD). METHODS: From 2016 November to 2018 September, a retrospective study was performed for the patients of KD in our hospital. Five patients (two males, three females) were included in this study. The mean age of the patients at the time of surgery was 51.6 years (range, 37-64 years). Varisized prosthesis identical to the live model in a ratio of 1:0.85, 1:1, and 1:1.1 were fabricated by 3D printing. All patients (one in Lichtman IIIA stage, two in Lichtman IIIB stage, one in Lichtman IIIC stage, and one in Lichtman IV stage) were treated with lunate excision and 3D printing prosthetic arthroplasty. Visual analog scale score (VAS), the active movement of wrist (extension, flexion) and strength were assessed preoperatively and postoperatively. The Mayo Modified Wrist Score (MMWS), Disabilities of the Arm, Shoulder and Hand (DASH) Score, and patient's satisfaction were evaluated during the follow-up. RESULTS: Prosthesis identical to the live model in a ratio of 1:0.85 or 1:1 were chosen for arthroplasty. The mean operation time (range, 45 to 56 min) was 51.8 ± 4.44 min. Follow-up time ranged from 11 months to 33 months with the mean value of 19.4 months. The mean extension range of the wrist significantly increased from preoperative 44° ± 9.6° to postoperative 60° ± 3.5° (P < 0.05). The mean flexion range of the wrist significantly increased from preoperative 40° ± 10.6° to postoperative 51° ± 6.5° (P < 0.05). The active movement of wrist and strength were improved significantly in all patients. VAS was significantly reduced from 7.3 preoperatively to 0.2 at the follow-up visit (P < 0.05). The mean DASH score was 10 (range, 7.2-14.2), and the mean MMWS was 79 (range, 70-90). There were no incision infection. All patients were satisfied with the treatment. CONCLUSIONS: For patients suffering advanced Kienböck's disease, lunate excision followed by 3D printing prosthetic arthroplasty can reconstruct the anatomical structure of the carpal tunnel, alleviate pain, and improve wrist movement.

Morphological Study of the Articular Disc and Capillary of the Retrodiscal Tissue in a Type 2 Spontaneous Diabetes Mellitus Rat Model.

The objective of this study was to evaluate morphological changes at the articular disc of the temporomandibular joint and capillary of the retrodiscal tissue in a rat model for type 2 spontaneous diabetes mellitus (DM) (i.e., Goto-Kakizaki [GK] rats) compared to normal Wistar rats. A total of 20 experimental rats were used in this study; the rats were categorized into the normal (n = 10 male 8-week-old Wistar rats) and DM (n = 10 male 8-week-old GK rats) groups. Hematoxylin-eosin stained specimens were obtained from 5 rats from each group. Image analyses of the hematoxylin-eosin stained specimens were conducted using light micrographs, which allowed comparisons of the thickness of the anterior, central, and posterior parts of the articular disc. Afterwards, the microvascular corrosion cast specimens were obtained from 5 rats from each group. The diameter of the capillary of the retrodiscal tissue was determined by analyzing scanning electron micrographs of the microvascular corrosion cast specimens. Student's t-test was used to test for statistical significant differences between the 2 groups. Differences were considered significant when p < 0.01. We found that the thickness of the anterior, central, and posterior parts of the articular disc, and the diameter of the capillary of the retrodiscal tissue was significantly lower in the DM vs. normal group. Therefore, we consider that DM-associated the hyperglycemia causes atrophy of the articular disc and microangiopathy of the capillary of the retrodiscal tissue in GK rats.

[Research progress of nano-hydroxyapatite complexes in bone tissue regeneration].

As the nano-hydroxyapatite is the main inorganic component of bone tissue of the human body, artificial synthesis of nano-hydroxyapatite has attracted the most attention in the field of hard tissue repair. To make up multiple aspects of limitations for nano-hydroxyapatite material itself, nano-hydroxyapatite complexes have been widely evaluated and applied in bone repair. This paper reviewed the common nano-hydroxyapatite complexes and their research progress in bone regeneration. Supported by Research Fund of Science and Technology Committee of Shanghai Municipality (12NM0501600, 13NM1402102) and Medicine and Engineering Cross Project of Shanghai Jiao Tong University (YG2012MS29).

Acrylic resin injection method for blood vessel investigations.

The injection of acrylic resin into vessels is an excellent method for macroscopically and microscopically observing their three-dimensional features. Conventional methods can be enhanced by removal of the polymerization inhibitor (hydroquinone) without requiring distillation, a consistent viscosity of polymerized resin, and a constant injection pressure and speed. As microvascular corrosion cast specimens are influenced by viscosity, pressure, and speed changes, injection into different specimens yields varying results. We devised a method to reduce those problems. Sodium hydroxide was used to remove hydroquinone from commercial methylmethacrylate. The solid polymer and the liquid monomer were mixed using a 1 : 9 ratio (low-viscosity acrylic resin, 9.07 ± 0.52 mPa•s) or a 3:7 ratio (high-viscosity resin, 1036.33 ± 144.02 mPa•s). To polymerize the acrylic resin for injection, a polymerization promoter (1.0% benzoyl peroxide) was mixed with a polymerization initiator (0.5%, N, N-dimethylaniline). The acrylic resins were injected using a precise syringe pump, with a 5-mL/min injection speed and 11.17 ± 1.60 mPa injection pressure (low-viscosity resin) and a 1-mL/min injection speed and 58.50 ± 5.75 mPa injection pressure (high-viscosity resin). Using the aforementioned conditions, scanning electron microscopy indicated that sufficient resin could be injected into the capillaries of the microvascular corrosion cast specimens.

Case-based learning in clinical courses in a Chinese college of stomatology.

As a medical approach to posing contextualized questions that are based on real-life clinical problems, case-based learning (CBL) is used to stimulate and underpin the acquisition of knowledge, skills, and attitudes through clinical cases. Good effects were acquired in the practice of CBL teaching in English applied by the College of Stomatology, Shanghai Jiao Tong University. Responses from both students and teachers reflected that this course approach won their high acceptance and was worthy of use in selected stomatological courses.

Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs.

Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and thus have a great potential in application in engineered bone substitutes with bioactive scaffolds in regeneration medicine. In the current study we characterized and demonstrated the pluripotency and osteogenic differentiation of mouse iPSCs. To enhance the osteogenic differentiation of iPSCs, we then transduced the iPSCs with the potent transcription factor, nuclear matrix protein SATB2. We observed that in SATB2-overexpressing iPSCs there were increased mineral nodule formation and elevated mRNA levels of key osteogenic genes, osterix (OSX), Runx2, bone sialoprotein (BSP) and osteocalcin (OCN). Moreover, the mRNA levels of HoxA2 was reduced after SATB2 overexpression in iPSCs. The SATB2-overexpressing iPSCs were then combined with silk scaffolds and transplanted into critical-size calvarial bone defects created in nude mice. Five weeks post-surgery, radiological and micro-CT analysis revealed enhanced new bone formation in calvarial defects in SATB2 group. Histological analysis also showed increased new bone formation and mineralization in the SATB2 group. In conclusion, the results demonstrate that SATB2 facilitates the differentiation of iPSCs towards osteoblast-lineage cells by repressing HoxA2 and augmenting the functions of the osteoblast determinants Runx2, BSP and OCN.

[Bilingual teaching in stomatological education in China: problems and future strategies].

Bilingual teaching has been used for several years in many Colleges of Stomatology in China, but there are still some problems be solved in textbooks, training of teachers, methods of teaching, etc. This paper discusses the purpose, manners, problems and strategies of bilingual teaching in stomatology. We believe that the specialties of stomatology and the situations of China should be considered in conducting bilingual teaching. The purposes of bilingual teaching are to use English and/or Chinese to teach basic and clinical knowledge and skill in Stomatology, and enhance the English ability of the students as well. To achieve the purposes and improve the quality of bilingual teaching, a well-organized textbook and adequate qualified teachers are demanded, modern teaching medias and methods should be adopted, and a rational teaching quality evaluation system should be established and fulfilled.

[The application of case-based learning in English in teaching of clinical stomatological courses].

As a medical course approach of posing contextualized questions that are based upon "real life" clinical problems, case-based learning (CBL) is used to stimulate and underpin the acquisition of knowledge, skills, and attitudes by clinical cases. Good effects were acquired in the practice of CBL teaching in English applied by College of Stomatology, Shanghai Jiao Tong University. Responses from both students and teachers reflected that this course approach won their high acceptability, and was worthy of use in selected stomatological courses.

[Histological and ultrastructural variations after radiofrequency for soft palate in porcines].

PURPOSE: To investigate the histological and ultrastructural variations after radiofrequency volumetric reduction of the soft palate in an animal model. METHODS: Thirteen porcines were used to evaluate the tissue response to radiofrequency for various time periods. They were divided into two groups. Group 1 was exposed to radiofrequency in the midline of the soft palate with a constant energy of 2.4 KJ. Group 2 served as a control group. The animals in group 1 were sacrificed after 1 hour, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 9 weeks, respectively, and after 72 hours, 2 weeks and 4 weeks for the animals in group 2. Then the soft palates from both groups were examined for histological and ultrastructural variations. RESULTS: Interstitial edema, hemorrhage and infiltration with inflammatory cells were observed in the early acute stage after radiofrequency, and then the neovascularization of the forming scar was observed. In the end, the injured tissue was replaced by collagenous fibers. Intact vessels and nerves were observed around the lesions. CONCLUSIONS: After radiofrequency, lesion tissue is replaced by collagenous fibers, and it is focused on the lesion site. These findings may help provide a basis for technological suggestion in regard to clinical treatment.