Designing nanohesives for rapid, universal, and robust hydrogel adhesion.

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.

[Progress in Application of Concentrated Growth Factor in Oral Tissue Regeneration].

Tissue regeneration is an important engineering method for the treatment of oral soft and hard tissue defects.Growth factors,as one of the three elements of tissue regeneration,are a necessary condition for tissue regeneration.Concentrated growth factor(CGF)is a new generation of blood extract prepared by changing the centrifugal speed on the basis of the preparation of platelet-rich plasma(PRP)and platelet-rich fibrin(PRF).It contains abundant growth factors and a fibrin matrix with a three-dimensional network structure,being capable of activating angiogenesis and promoting tissue regeneration and healing.CGF has been widely used in the repair and regeneration of oral soft and hard tissues.This paper introduces the preparation and composition of CGF and reviews the application of CGF in oral implantation and the regeneration of oral bone tissue,periodontal tissue,and dental pulp tissue.

A Study of Two Novel Techniques for One-stage Closure of Chronic Oroantral Fistula and Sinus Floor Lift.

PURPOSE: This study aimed to compare two novel techniques for chronic oroantral fistula (OAF) closure combined with maxillary sinus floor elevation. MATERIALS AND METHODS: Ten patients who had implant installation needs but suffered from a chronic OAF were enrolled in the study from January 2016 to June 2021. The technique applied involved OAF closure and simultaneous sinus floor elevation by either a transalveolar or lateral window approach. Bone graft material evaluation results, postoperative clinical symptoms and complications were compared between the two groups. Student's t -test and χ 2 test were used to analyze the results. RESULTS: In this study, 5 patients with a chronic OAF were treated with the transalveolar approach (group I), and 5 were treated with the lateral window approach (group II). The alveolar bone height was significantly higher in group II than in group I ( P ＜0.001). The pain at 1 day ( P =0.018) and 3 days ( P =0.029) postoperatively and facial swelling at 7 days ( P =0.016) postoperatively were obviously greater in group II than in group I. There were no severe complications in either group. CONCLUSIONS: The techniques combined OAF closure with sinus lifting to reduce surgical frequency and risks. The transalveolar approach resulted in milder postoperative reactions, but the lateral approach could provide more bone volume.

[Effect of rat allogeneic BMSCs-Bio-Oss-bFGF compound on tooth extraction healing: a micro-CT study].

PRUPOSE: To investigate the effect of a compound of BMSCs-Bio-Oss-bFGF on microstructure of extraction sockets in rats. METHODS: Bone mesenchymal stem cells (BMSCs) were isolated from bone marrow of 3-week SD rats by adherent method. Maxillary posterior teeth of 36 6-week SD rats were extracted and materials were implanted into sockets according to grouping. The rats were divided into 4 groups: compound group with implanting BMSCs-Bio-Oss-bFGF compound, powder group with implanting Bio-Oss, BMSCs group with implanting BMSCs, and control group without implanting any materials. The sockets were scanned by micro-CT 4 weeks, 12 weeks and 24 weeks after implantation. Two-way ANOVA was used to assess whether there was significant difference between groups with GraphPad Prism 6.0 software package. RESULTS: There was no significant difference among groups in bone mineral density (BMD), trabecular separation(Tb.Sp), trabecular thickness(Tb.Th), degree of anisotropy(DA), and trabecular number(Tb.N) 4 weeks after implantation. By 12 weeks, BMD of compound group was significantly greater than those of BMSCs group, powder group and control group (P＜0.05), and significantly greater than those of powder group and control group at 24 weeks (P＜0.05). Tb.Th of compound group was significantly greater than that of BMSCs group at 12 and 24 weeks(P＜0.05). DA had no significant difference among groups at 4, 12, and 24 weeks (P＞0.05). Tb.Sp of compound group was significantly smaller than those of powder group, BMSCs group and control group at 24 weeks(P＜0.05). Tb.N of compound group was significantly greater than those of BMSCs group and control group(P＜0.05). CONCLUSIONS: The compound of rat allogeneic BMSCs-Bio-Oss-bFGF improves socket healing.

Anti-Swelling, Robust, and Adhesive Extracellular Matrix-Mimicking Hydrogel Used as Intraoral Dressing.

Due to the wet and dynamic environment of the oral cavity, the healing of intraoral wounds, such as tooth extraction wounds, requires stable and firm wound dressings. In clinical practice, cotton balls and gauzes, sponge plugs, or sutures are used to treat extraction wounds, but none of these means can continuously isolate the wound from the intraoral environment and facilitate ideal healing conditions. Herein, inspired by the natural extracellular matrix, a family of wound dressings is developed for intraoral wound repair. Infiltrating a ductile long-chain hydrogel network into a prefabricated, sturdy macromolecular meshwork and in situ crosslinking endowed the composite hydrogel with controllable swelling behaviors and robust mechanical properties. The macromolecular meshwork functioned as the backbone to support the composite and restricts the swelling of the long-chain hydrogel network. In vitro tests verified that this wound dressing can provide durable protection for intraoral wounds against complex irritations. Furthermore, accelerated wound healing occurred when the wound dressing is applied in vivo on a canine tooth extraction model, due to the effective reduction of acute inflammation. These results suggest that this family of bioinspired hydrogels has great potential for application as intraoral wound dressing.

[The hemostasis effect and cell compatibility of a chitosan-calcium alginate-laponite nanosheet composite membrane: in vitro and in vivo evaluation].

PURPOSE: To explore the feasibility of a chitosan-calcium alginate-laponite nanosheet composite membrane being used as a new hemostatic membrane for wounds in oral cavity. METHODS: The composite membrane was prepared in a layered fashion: the lower layer of chitosan membrane was made through self-evaporation and the upper layer of calcium alginate-laponite nanosheet sponge was made via freeze-drying. The microstructure of the composite membrane was observed under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). X-ray diffraction was used as a means of identifying the compounds. Clotting time of composite membrane, medical gauze and Chitin dressing in vitro was measured by the plate method for blood coagulation. Cytotoxicity tests were quantified through co-culturing NIH/3T3 cells with chitosan-calcium alginate extract, composite hemostatic membrane extract and DMEM. Superficial buccal mucosal wound models and tooth extraction models were created on beagles dogs, the hemostatic effect and adhesion to oral mucosa were evaluated on these models. Statistical analysis was performed using SPSS 18.0 software package. RESULTS: The composite hemostatic membrane consisted of double-layer in microstructure, the upper layer was a foam layer consisting of calcium alginate and laponite nanosheet, the substratum was formed by uniform chitosan film. X-ray diffraction results showed that laponite nanosheet can be found in the composite membrane. Coagulation test showed that the composite hemostatic membrane group significantly shortened clotting time in vitro compared to pure calcium alginate group, commercial hemostatic membrane and blank control group(P＜0.001). CCK-8 test of NIH/3T3 cell showed that there was no significant difference in absorbance between the experimental group, negative control group and blank control group (P＞0.05). In addition, composite hemostatic membrane displayed a good hemostatic effect and strong adhesion to oral mucosa in animal models. CONCLUSIONS: The composite hemostatic membrane showed great hemostatic effects and had no significant cytotoxicity, which has the potential for clinical application as hemostatic membrane for wounds in oral cavity.

[Effect evaluation on different treatment methods of the gap of immediate implantation in canine posterior mandible].

PURPOSE: This study was aimed to explore the formation of new bone after different methods of filling the gap between the extraction socket and the implant in immediate implantation of the canine mandibular molar area. METHODS: Six Labrador dogs aged 1.5-2.0 years were used as the experimental subjects. The fourth premolar and the first molar were extracted from the mandible of each dog, and then 4 dental implants (Astra Tech, 4.0 mm × 10 mm) were implanted respectively. The mesial and distal gaps between dental implants and the walls of extraction socket were treated in three methods: blank group (group NN), gelatin sponge with colloidal silver (Gelatamp) group (group EN), Gelatamp + absorbable collagen membrane (CM) group (group EG). At 12 weeks, the dogs were euthanized, and specimens were collected for micro-CT scanning and histological analysis. SPSS 25.0 software package was used for statistical analysis. RESULTS: The survival rate at 12 weeks after implantation was 100%. Micro-CT scan results showed no significant differences in new bone height, bone mineral density (BMD), bone volume fraction (BV/TV), bone surface area bone volume ratio (BS/TV), bone trabecular thickness (Tb.Th), bone trabecular number (Tb.N) and bone trabecular separation (Tb.Sp) among different groups. Histological analysis showed no significant differences in the area of new bone formation and bone-implant contact (BIC). CONCLUSIONS: After different treatments are performed on the gap between implants and extraction sockets, Gelatamp alone or in combination with CM has no significant effect on new bone formation, BIC, BMD, BV/TV, BS/TV, Tb.Th, Tb.N and Tb.Sp around implant.

Quantitative Segmentation Analysis of the Radiological Changes by Using ITK-SNAP: Risk Assessment of the Severity and Recurrence of Medication-related Osteonecrosis of the Jaw.

Background and purpose: Medication-related osteonecrosis of the jaw (MRONJ) severely impairs patients' quality of life and is remarkably refractory to treatment. There are lots of studies about identification of the radiographic features of MRONJ, yet reports about quantitative radiographic analysis for the risk assessment of the severity and recurrence of MRONJ are rarely heard. The aim of this study was to investigate the volumes of osteolytic lesions and radiodensity values of osteosclerotic lesions in MRONJ patients by using ITK-SNAP for severity prediction and prognosis evaluation. Materials and methods: Of 78 MRONJ patients (78 lesions) involved in this retrospective study, 53 were presented as osteolytic lesions and 25 were presented as osteosclerotic changes alone. Comprehensive CBCT images, demographics and clinical data of patients were investigated. The volumetric analysis and radiodensity measurement were performed by ITK-SNAP. SPSS 25.0 were used for statistical analysis. Results: The osteolytic lesion volumes in MRONJ patients receiving intravenous bisphosphonates (P=0.004) and patients without osteoporosis (P=0.027) were significantly large. No significant correlation between the volumes and bisphosphonates duration was found (P=0.094). The radiodensity values of osteosclerotic lesions was significantly correlated with bisphosphonates duration (P=0.040). The surrounding area of post-surgical lesions in MRONJ patients with recurrence showed significantly great radiodensity values (P=0.025). No significant correlation between the radiodensity values and the transformation from osteosclerotic lesions to osteolytic lesions was observed (P=0.507). Conclusion: MRONJ patients receiving intravenous bisphosphonates develop into large volumes of osteolytic lesions more easily. Long-term bisphosphonates duration is possibly related with higher bone density of osteosclerotic lesions, while higher density is not associated with the transformation from osteosclerotic lesions to osteolytic lesions. A rise of bone mineral density nearby post-surgical lesions is probably a predictor for MRONJ recurrence.

Iron oxide nanoclusters for T 1 magnetic resonance imaging of non-human primates.

Iron-oxide-based contrast agents for magnetic resonance imaging (MRI) had been clinically approved in the United States and Europe, yet most of these nanoparticle products were discontinued owing to failures to meet rigorous clinical requirements. Significant advances have been made in the synthesis of magnetic nanoparticles and their biomedical applications, but several major challenges remain for their clinical translation, in particular large-scale and reproducible synthesis, systematic toxicity assessment, and their preclinical evaluation in MRI of large animals. Here, we report the results of a toxicity study of iron oxide nanoclusters of uniform size in large animal models, including beagle dogs and the more clinically relevant macaques. We also show that iron oxide nanoclusters can be used as T 1 MRI contrast agents for high-resolution magnetic resonance angiography in beagle dogs and macaques, and that dynamic MRI enables the detection of cerebral ischaemia in these large animals. Iron oxide nanoclusters show clinical potential as next-generation MRI contrast agents.

Chitosan microspheres with an extracellular matrix-mimicking nanofibrous structure as cell-carrier building blocks for bottom-up cartilage tissue engineering.

Scaffolds for tissue engineering (TE) which closely mimic the physicochemical properties of the natural extracellular matrix (ECM) have been proven to advantageously favor cell attachment, proliferation, migration and new tissue formation. Recently, as a valuable alternative, a bottom-up TE approach utilizing cell-loaded micrometer-scale modular components as building blocks to reconstruct a new tissue in vitro or in vivo has been proved to demonstrate a number of desirable advantages compared with the traditional bulk scaffold based top-down TE approach. Nevertheless, micro-components with an ECM-mimicking nanofibrous structure are still very scarce and highly desirable. Chitosan (CS), an accessible natural polymer, has demonstrated appealing intrinsic properties and promising application potential for TE, especially the cartilage tissue regeneration. According to this background, we report here the fabrication of chitosan microspheres with an ECM-mimicking nanofibrous structure for the first time based on a physical gelation process. By combining this physical fabrication procedure with microfluidic technology, uniform CS microspheres (CMS) with controlled nanofibrous microstructure and tunable sizes can be facilely obtained. Especially, no potentially toxic or denaturizing chemical crosslinking agent was introduced into the products. Notably, in vitro chondrocyte culture tests revealed that enhanced cell attachment and proliferation were realized, and a macroscopic 3D geometrically shaped cartilage-like composite can be easily constructed with the nanofibrous CMS (NCMS) and chondrocytes, which demonstrate significant application potential of NCMS as the bottom-up cell-carrier components for cartilage tissue engineering.

[Establishment and assessment of tibial osteoradionecrosis in rats].

PURPOSE: To establish a rat tibial osteoradionecrosis model and assess the model by observing clinical manifestation and histopathological examinations. METHODS: The right tibia of 6 Sprague Dawley (SD) rats (weighing 200-250 g) was irradiated by a linear accelerator (single fraction 15 Gy, total dose 60 Gy) every second week for four times. Hair and cutaneous changes of the irradiated region were observed one, two, three and four weeks after irradiation, respectively. Histopathological examination was employed to compare the bone tissue between the irradiated region and irradiation-free region. X-ray film was taken to evaluate the bone destruction. SPSS13.0 software package was used for statistical analysis. RESULTS: One week after irradiation, no significant change was observed in the irradiated region. However, the palm of the irradiated limb turned red remarkably in contrast with the opposite one. Two and three weeks after irradiation, trichomadesis was observed in the irradiated region. Four weeks after irradiation, complete trichomadesis and skin ulceration occurred in the irradiated region. In histopathological examinations, hematoxylin-eosin staining showed that bone mass including bone plate thickness, bone marrow cell, bone trabecula decreased significantly in the irradiated region compared with the control side. Moreover, significant bone destruction was found in irradiated group. CONCLUSIONS: We have successfully established a rat tibial model of osteoradionecrosis with radiation at dosage of 60 Gy divided into 4 times.

[Research advances in peri-implantitis relevant factors and therapy].

Peri-implantitis has been defined as an inflammatory process affecting tissues around an osseo-integrated implant in function, and resulting in the loss of supportive alveolar bone. As it was one of the main causes which led to the failure of implant treatment, its risk factors and treatment were attracting more and more attention. This review summarized the progress of clinical research on peri-implantitis risk factors and treatments.

[The study of osteogenic differentiation in canine bone marrow stromal cell induced by point mutant type of HIF-1α].

PURPOSE: To evaluate osteogenesis in canine bone marrow mesenchymal stem cells(BMSCs) transduced by point mutant HIF-1α. METHODS: Lenti-WT (wild type HIF-1α), Lenti-MT (mutant type HIF-1α), and Lenti-LacZ (the control group) were constructed with LR recombination system. And then Lenti-LacZ, Lenti-WT and Lenti-MT were used to transduce canine BMSCs. After transduction, total RNA and protein were extracted at 0 , 1 , 4 , 7, 14 d and 21 d, respectively. The mRNA and protein expression of osteogenic factors were detected by RT-PCR and Western blot in vitro under normoxic conditions.To further prove osteogenic differentiation of HIF-1α mediated BMSCs, the BMSCs were inoculated into 6-well plate (2×10(5)/well) and then the expression of calcium nodules was measured using Alizarin red staining(ARS) at 14 d and 21 d, respectively. RESULTS: At MOI=9, the transduced efficiency of BMSCs was up to 90%. After target gene being transduced to BMSCs, the mRNA and protein expression of osteogenic factors were significantly up-regulated at 4d, reached peak at 14-21 d and maintained a state of high expression (P<0.05). ARS results showed that the target gene can induce BMSCs to the osteogenic differentiation in normoxic conditions. CONCLUSIONS: Under normoxic conditions in vitro, mutant HIF-1α can stabilize the expression and maintain a high level of activity. Lenti-MT can significantly improve the osteogenic activity of canine BMSCs.

[Construction and detection of gene expression vector of the Von Hippel-Lindau in bone marrow stromal cells].

PURPOSE: To construct siRNA-VHL expression vector and detect the effect of VHL gene interference on BMSCs. METHODS: According to the dog's VHL gene sequences, four pairs of siRNA oligo were designed and synthesized. Using vector cloning kit reorganization, four pairs of double-stranded siRNA were inserted into the expression vector (pcDNA™ 6.2-GW/EmGFPmiR) and 4 siRNA expression plasmids (SR144-1,SR144-2,SR144-3,SR144-4) were constructed. With the vector universal primers, colony PCR was screened. The positive clones were sequenced to verify whether the sequence of insert fragments in recombinant clones was consistent with oligo sequences designed or not. Interference vector transiently transfected the BMSCs. qPCR and Western blot were used to detect the gene silencing effect. In order to improve transfection efficiency of siRNA-VHL as well as the effect of the VHL gene silencing, pLenti-mi-VHL was constructed. RESULTS: Through sequencing the plasmids cloned, the fragment sequences inserted in recombinant clones were consistent with the designed oligo sequences. After 24 h and 48 h transfection of BMSCs cells by plasmids, SR144-4 showed the best effect of interference by qPCR and Western blot. Through comparing the sequencing results, the inserted fragment sequences were completely correct and the pLenti-mi-VHL was successfully constructed. CONCLUSION: The siRNA-VHL expression vector for BMSCs is successfully constructed and applicable for further experiments. Supported by Research Fund of Science and Technology Commission of Shanghai Municipality (Grant No.9411954800) and Foundation for Open Project from Shanghai Key Laboratory of Stomatology (Grant No.S30206).