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Retention of foreign bodies frequently happened in the region of oral and maxillofacial. In very rare cases, the positions of the foreign objects moved with the movement of muscles in the oral and maxillofacial regions. Precise locations of moving objects and minimally invasive surgeries pose a great challenge to surgeons. The case of a 44-year-old female patient diagnosed with retention of the fractured needle is reported in this study. A digital guide plate was manufactured to locate the precise position of the fractured needle and preoperatively mimic the surgery processes. The computerized navigation system guided us to make an incision and precisely target the fractured needle during the surgery. Combing the technologies of the digital guiding plate and navigation system, removing the moving foreign bodies becomes objective, time-saving, and minimally invasive.
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Corpos Estranhos , Cirurgia Assistida por Computador , Feminino , Humanos , Adulto , Cirurgia Assistida por Computador/métodos , Cabeça , Procedimentos Cirúrgicos Minimamente Invasivos , Agulhas , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgiaRESUMO
PURPOSE: Screw osteosynthesis is advocated for the treatment of sagittal fracture of mandibular condyle (SFMC). This study aimed to explore the applicability of resorbable-screw osteosynthesis in the treatment of SFMC. METHODS: A retrospective cohort study was performed in patients with SFMC treated with resorbable-screw osteosynthesis (group A) from June 2011 through June 2021. The patients who had undergone titanium-screw osteosynthesis served as the control group (group B). The primary outcome variable was fracture healing, defined as follows: 1) normal mouth opening and restoration of pretrauma occlusion; 2) without complications or discomfort of temporomandibular joint symptoms; and 3) fracture union without abnormal reactions or bone resorption in computed tomography images. The secondary outcome variable was condylar morphological changes including radiographic imaging appearance of the condyle, mandibular ramus height (MRH), anteroposterior diameter (APD), and mediolateral diameter (MLD) of the condyle, which were assessed by comparing the computed tomography images 1 week after surgery with those of 3 months after surgery. The collected data of the outcome variables of the 2 groups were analyzed correspondingly using Student's paired t test and Student's t test. RESULTS: There were 24 patients in group A and 71 patients in group B. All the patients displayed an evident improvement in mouth opening and restored pretrauma occlusion. Few patients had complications (group A, 8.33%; group B, 9.86%) and discomfort of temporomandibular joint symptoms (group A, 16.67%; group B, 15.49%). Fracture union without abnormal reactions or bone resorption was observed during the follow-up. The radiographic evaluation revealed no significant difference in the MRH, the maximum APD, and MLD of the condyles between 1 week and 3 months after surgery in both groups. There were no significant intergroup differences in the changes in the MRH, APD, and MLD of the condyles. CONCLUSIONS: Resorbable-screw osteosynthesis is a viable option for the treatment of SFMC.
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Reabsorção Óssea , Fraturas Mandibulares , Reabsorção Óssea/etiologia , Parafusos Ósseos/efeitos adversos , Fixação Interna de Fraturas/métodos , Humanos , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/lesões , Côndilo Mandibular/cirurgia , Fraturas Mandibulares/complicações , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: In this study, we aimed to describe a multimedia-supported manikin system, compare the new manikin with the traditional manikin and evaluate its effectiveness in preclinical dentistry training. METHODS: A total of 150 students participated in this study. Amongst these students, 71 in the 2015-year group used traditional manikins (Group TM) for preclinical training courses (endodontics training courses and prosthodontics training courses), and 79 in the 2016-year group used manikins with a multimedia system (Group MM). The scores of the training courses between the two groups were compared. A questionnaire survey was used to collect opinions of the students in Group MM on their experience of using the multimedia-supported manikin system in the preclinical training. RESULTS: In the endodontics training courses, the scores of Group MM were higher than those of Group TM, but there was no significant difference (P = 0.379 > .05). However, the scores of prosthodontics training courses in Group MM were significantly higher than those in Group TM (P = 0.018 < .05). The questionnaire results indicated that the students in Group MM were satisfied with the device in usability, clarity, effectiveness and improvement in operation proficiency. CONCLUSIONS: In the groups studied, for preclinical dental training, the multimedia-supported manikin system was a good alternative to traditional manikin in preclinical dentistry training.
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Manequins , Multimídia , Educação em Odontologia/métodos , Avaliação Educacional , Humanos , Prostodontia/educaçãoRESUMO
CCN2, also known as connective tissue growth factor (CTGF), is a 38 kDa cysteine-rich extracellular matrix protein that regulates a sequence of cellular functions and participates in multiple complex biological processes, such as chondrogenesis and osteogenesis. In the present study, we provided the first evidence describing the physiological role of CCN2 in condylar chondrocyte proliferation, migration, maturation and differentiation. CCN2 was widely expressed throughout the whole layers of condylar cartilage and predominantly distributed in the proliferative zone. Recombinant CCN2 promoted the proliferation, migration, proteoglycan synthesis and differentiation capacity of isolated condylar chondrocytes. The stimulatory effect of CCN2 on chondrocyte proliferation was associated with the activation of phosphatidylinositol 3-kinase/Akt signalling pathway. The blocking of this pathway by its inhibitor LY294002 impaired the proliferative effect of CCN2 on chondrocytes. These results suggested a novel physiological role of CCN2 in the development of condylar cartilage.
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Condrócitos/citologia , Condrócitos/fisiologia , Condrogênese/fisiologia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Côndilo Mandibular/citologia , Côndilo Mandibular/metabolismo , Animais , Diferenciação Celular/fisiologia , Crescimento Celular , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologiaRESUMO
Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia-induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia-induced BMSCs migration and osteogenic differentiation. BMSCs isolated from C57BL/6 male mice were cultured in the presence of cobalt chloride (CoCl2 ) to simulate intracellular hypoxia. Hypoxia enhanced BMSCs migration, and upregulated cell migration related gene expression, that is, metalloproteinase (MMP) 7, MMP9, and C-X-C motif chemokine receptor 4. Hypoxia enhanced the phosphorylation of STAT3, and cell migration related proteins: c-jun n-terminal kinase (JNK), focal of adhesion kinase (FAK), extracellular regulated protein kinases, and protein kinase B 1/2 (ERK1/2). Moreover, hypoxia enhanced expression of osteogenic differentiation marker. Inhibition of STAT3 suppressed the hypoxia-induced BMSCs migration, cell migration related signaling molecules phosphorylation, and osteogenic differentiation related gene expression. In conclusion, our result indicates that hypoxia-induced BMSCs migration and osteogenic differentiation is via STAT3 phosphorylation and involves the cooperative activity of the JNK, FAK, and MMP9 signaling pathways.
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Células-Tronco Mesenquimais/efeitos dos fármacos , Fator de Transcrição STAT3/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cobalto/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipóxia/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Metaloproteinase 7 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/genética , Fosforilação , Receptores CXCR4/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: It has traditionally been difficult to create full-thickness defects in the mandibles of rodent animals because of dissimilar anatomic structures with humans, interference from teeth of jaws, and limited surgical access. To better mimic the cellular situation and the unique masticatory stresses in maxillofacial regions of humans, we developed an animal model of mandibular defects, in which rabbits were implanted with the beta-tricalcium phosphate/chitosan (ß-TCP/CS) scaffolds after a dental extraction and the creation of a full-thickness bone defect. METHODS: Seventy-two New Zealand rabbits underwent unilateral mandibular defect surgery in the premolar region and were randomly divided into three groups as follows: (1) The full-thickness bicortical defect with tooth extraction of the mandibular first premolar and implantation of bone marrow stromal cells/ß-TCP/CS scaffold graft (group G + E); (2) the bicortical defect, not treated with tooth extraction and implanted with the bone marrow stromal cells/ß-TCP/CS grafts (group G); and (3) the bicortical defects created in the same location in the negative control group, not treated with tooth extraction and graft implantation (group C). The defects in all groups were examined at 4 and 12 wk using mechanical tests, x-ray, and histology observation to determine the biomechanical stability, quantity, and quality of the newly formed bone. RESULTS: Group G + E displayed the largest amount of new bone formation, with high mechanical forces in compression and three-point bending tests, filled in the mandibular defects at 4 wk, and complete reconstruction of bony contours and bridging by 12 wk after implantation. Although similar mechanical forces and new bone formation were demonstrated by the normal healing specimens, the abnormal cases with periapical diseases of group G demonstrated less amount of new bone formation and smaller mechanical forces when compared with those of group G + E at 4 and 12 wk. In contrast, the defect without graft implantation in the negative control group (group C) failed to bridge itself and displayed fibrous tissue filled in the defects with the lowest mechanical forces at both 4 and 12 wk of implantation. CONCLUSIONS: A 10-mm diameter, full-thickness mandibular defect treated with tooth extraction of the first mandibular premolar can mimic the segmental jawbone defects and fulfill the requirements of a critical-size mandibular defect in rabbits. Furthermore, the new bone regeneration and biomechanical stability of the mandible can be promoted by extraction of the teeth located in the defect side, which demonstrated the potential of this model as a test bed for tissue-engineering grafts used in jawbone defects.
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Modelos Animais de Doenças , Traumatismos Mandibulares , Animais , Peso Corporal , Remodelação Óssea , Força Compressiva , Ingestão de Alimentos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Coelhos , Radiografia , Distribuição Aleatória , Alicerces Teciduais , Extração DentáriaRESUMO
Bone tissue engineering is bringing hope to patients with jawbone defects, but this technology works well only for small- to moderate-sized jawbone defects. For large segmental jawbone defects, it is difficult to form the functional vascular networks within the graft due to limited diffusion of nutrition and uneven distribution of seed cells. From the standpoint of bionics, seed cells should be continuously transmitted into the graft to replace the necrotic cells during the entire process of bones regeneration. However, the existing one-time inoculation method (OIM) fails to achieve this goal because it is almost impossible to re-open the wound and inoculate cells into grafts that have already been implanted into the body. Inspired by the anatomical structure of jawbones, we hypothesize that the root canal in teeth of jawbones could be used as a channel through which seed cells could be delivered into the graft. Therefore, the multiple-times inoculation method (MIM) could be achieved via the root canal system if defects are located on the maxillofacial bones with teeth. Both osteogenesis and vascularization would be promoted to a large extent because the engineered construct has a limitless supply of seed cells and growth factors.
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Transplante de Células , Cavidade Pulpar/fisiologia , Engenharia Tecidual/métodos , Humanos , Modelos BiológicosRESUMO
Degradation profiles are critical for the optimal application of electrospun polymer nanofibers in tissue regeneration, wound healing, and drug delivery systems. In this study, natural and synthetic polymers and their composites were subjected to in vivo transplantation and in vitro treatment with lipases, macrophages, and acetic acid to evaluate their degradation patterns. The effects of environmental stimulation, surface wettability, and polymer components on the degradation profiles of the electrospinning poly(ε-caprolactone)/silk fibroin (PCL/SF) nanofibers were first evaluated. In vivo degradation study demonstrated that bulk degradation, characterized by the transition from microfibers to nanofibers, and surface erosion, characterized by fusion between the microfibers or direct erosion from both ends of the microfibers, occurred in the electrospun membranes; however, bulk degradation dominated their overall degradation. Furthermore, the degradation rates of the electrospun PCL/SF membranes varied according to the composition, morphology, and surface wettability of the composite membranes. After the incorporation of silk fibroin (SF), the degradation rate of the SF/PCL composite membranes was faster, accompanied by larger values of weight loss and molecular weight (Mw) loss when compared with that of the pure poly(ε-caprolactone) (PCL) membrane, indicating a close relationship between degradation rate and hydrophilicity of the electrospinning membranes. The in vitro experimental results demonstrated that enzymes and oxidation partially resulted in the surface erosion of the PCL/SF microfibers. Consequently, bulk degradation and surface erosion coordinated with each other to enhance the hydrophilicity of the electrospinning membranes and accelerate the in vivo degradation.
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Fibroínas , Poliésteres , Engenharia Tecidual , Fibroínas/química , Poliésteres/química , Engenharia Tecidual/métodos , Animais , Nanofibras/química , Membranas Artificiais , Camundongos , Molhabilidade , Alicerces Teciduais/química , Materiais Biocompatíveis/químicaRESUMO
In order to quantitatively calculate the critical depth and critical load of mines affected by rock burst, and to achieve effective prevention and control of rock burst in coal mines, this paper proposes a mechanical model for predicting the occurrence of rock burst in coal mine roadways based on catastrophe theory. Additionally, a theoretical calculation formula for initiating rock burst is derived. The first step was to establish a mechanical analysis model, which directly correlated with the in-situ stress, physical and mechanical characteristics of the coal-rock mass, and engineering structural parameters. Following this, a mechanical instability criterion was derived for the key load-bearing circle within the surrounding rock of the roadway. In the final step, the critical depth and load for rock burst initiation were verified for 25 distinct coal mines in China that were prone to rock burst hazards. The research results demonstrate that the discrepancy between the theoretically calculated critical depth and the actual measured statistical values was less than 35%. In addition, the difference between the theoretically determined critical depth and the value calculated by Pan Yishan was less than 32%. Notably, the ratio of the theoretically calculated critical load to the uniaxial compressive strength of the coal-rock mass ranged from 0.38 to 1.93. This aligns with empirical data on rock burst occurrences, as set out in the engineering classification standards for rock masses. These research outcomes substantiated the practical utility of the proposed theory, thereby laying a robust theoretical groundwork for the quantitative control of rock burst.
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The guided bone regeneration (GBR) membranes currently used in clinics are usually compromised by their limited osteogenic induction potential. In this study, we fabricate a core-shell poly(ε-caprolactone)/chitosan/polyvinyl alcohol (PCL/CS/PVA) GBR membrane with different amount of resveratrol (RSV), endowing the PCL/CS/PVA GBR membrane with superior osteogenic induction ability, which was not attained by the regular GBR membrane. The prepared GBR membranes were characterized by scanning electron microscopy, transmission electron microscopy, and CCK-8 and live-dead staining assays, and their osteogenic induction ability was evaluated using Col-I immunofluorescence staining, micro-computed tomography, haematoxylin and eosin staining and immunohistochemical staining. Results of the in vitro release experiment confirmed that the membranes exhibited a continuous RSV release profile for 15 days. Furthermore, the cumulative releasing of RSV was increased from 39.68 ± 2.09 µg to 65.8 ± 2.91 µg with increasing contents of RSV from 0.1 % to 0.5 % (w/v) in the core layer of GBR membranes. In particular, the PCL/CS/PVA GBR membrane loading with 0.5 % RSV most efficiently release RSV in a sustained and controlled manner, which significantly induced osteogenic differentiation of pre-osteoblasts in vitro and bone regeneration in vivo. Based on the in vivo histological findings, newly formed bone tissues with 82.46 ± 9.86 % BV/TV and 0.70 ± 0.07gcm-3 BMD were generated in the defect sites treated by the GBR membrane loaded with 0.5 % RSV, which were the largest values among those for all three groups after 12 weeks of post implantation. Overall, the PCL/CS/PVA GBR membrane loaded with 0.5 % RSV has significant potential for bone regeneration.
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Quitosana , Osteogênese , Quitosana/química , Resveratrol/farmacologia , Materiais Biocompatíveis/química , Microtomografia por Raio-X , Álcool de Polivinil , Regeneração Óssea , Poliésteres/química , Membranas ArtificiaisRESUMO
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a serious life threatening clinical critical illness. ARDS-related pulmonary fibrosis is a common complication of ARDS. The occurrence of early pulmonary fibrosis indicates a higher incidence and mortality of multiple organ failure. LPS-induced ARDS-related pulmonary fibrosis model in mice was established in this study. And we have explored the anti-pulmonary fibrosis effects and molecular mechanisms of the Citrus Alkaline Extracts (CAE) in vivo and in vitro. METHODS: Pulmonary fibrosis mouse model and lung epithelial cell injury model were established in this study. H&E, Masson and Sirius Red staining were used to estimate lung tissue damage. Immunohistochemistry and western blotting were used to analyze proteins expression. Protein-protein interaction was observed by Co-Immunoprecipitation. Systemic impact of CAE on signaling pathway was examined by RNA-seq. RESULTS: Through H&E, Masson and Sirius Red staining, it was convincingly indicated that therapeutic administration of CAE alleviated lung injury and fibrosis, while pretreated administration of CAE showed weak improvement. In vitro experiments showed that CAE had dual regulation to E-cadherin and N-cadherin, the important indicators of epithelial-mesenchymal transition (EMT). And it was further demonstrated that CAE reversed TGF-ß1-induced EMT mainly through Wnt/ß-catenin, Stat3/6 and COX2/PGE2 signals. Through RNA-Seq, we discovered important mechanisms by which CAE exerts its therapeutic effect. And network pharmacology analysis demonstrated core potential targets of CAE in EMT. CONCLUSION: Thus, this study provides new therapeutic effects of CAE in anti-fibrosis, and offers potential mechanisms for CAE in LPS-induced pulmonary fibrosis.
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The complex or compromised bone defects caused by osteomyelitis, malignant tumors, metastatic tumors, skeletal abnormalities, and systemic diseases are difficult to be self-repaired, leading to a non-union fracture. With the increasing demands of bone transplantation, more and more attention has been paid to artificial bone substitutes. As biopolymer-based aerogel materials, nanocellulose aerogels have been widely utilized in bone tissue engineering. More importantly, nanocellulose aerogels not only mimic the structure of the extracellular matrix but could also deliver drugs and bioactive molecules to promote tissue healing and growth. Here, we reviewed the most recent literature about nanocellulose-based aerogels, summarized the preparation, modification, composite fabrication, and applications of nanocellulose-based aerogels in bone tissue engineering, as well as giving special focus to the current limitations and future opportunities of nanocellulose aerogels for bone tissue engineering.
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Laboratory course acts as a key component of histopathology education. Recent trends of incorporating visual and interactive technology in active and inquiry-based learning pedagogical methods have led to significant improvement of histopathology laboratory courses. The present work aimed to describe interactive virtual microscope laboratory system (IVMLS) as a virtual platform for teaching histopathology in order to improve the quality and efficiency of teaching. The system is based on interactive technology and consists of interactive software, slide-reading software, teaching resources and integrated auxiliary equipment. It allows real-time interaction between teachers and students and provides students with a wealth of learning and review materials. In order to evaluate the effectiveness of the system, we conducted a comparative study with the use of light microscope (LM) as a method. Specifically, we compared the results of six assignments and one laboratory final exam between IVMLS group and LM group to analyse the impact of IVMLS on students' academic performance. A questionnaire survey was also conducted to obtain students' attitudes and views on this system. There was no overall difference in assignment performance between IVMLS group and LM group. But laboratory final test grades increased from a mean of 62% (43.8-80.0, 95% CI) before to 83% (71.0-94.2, 95% CI) after implement IVMLS, suggesting highly significant (p < 0.001) improvement on students' histopathology laboratory performance. Feedback of the questionnaire was positive, indicating that students were satisfied with the system, which they believed improved student communication and teacher-student interaction, increased learning resources, increased their focus on learning, and facilitated their independent thinking process. This study proves that IVMLS is an efficient and feasible teaching technology and improves students' academic performance.
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Microscopia , Interface Usuário-Computador , Retroalimentação , Humanos , Laboratórios , Aprendizagem , Microscopia/métodosRESUMO
PURPOSE: To evaluate and compare the influence of different types of mandibular reconstruction on health-related quality of life (HR-QoL) of nonrecurrence patients. PATIENTS AND METHODS: We recruited 252 patients who underwent mandibular reconstruction between 1994 and 2007 for this cross-sectional study. They were classified into groups based on reconstruction technique: free bone graft (FBG) group, particulate bone cancellous marrow graft (PBCMG) group, reconstruction plate (RP) group, and microvascular free flap group. The University of Washington Head and Neck Quality of Life Questionnaire and 5 supplemental domains regarding the donor sites were used to evaluate and compare HR-QoL among the groups. RESULTS: The outcomes of the University of Washington Head and Neck Quality of Life Questionnaire differed significantly among the groups (P < .0001). The results of the additional donor site domains also differed greatly among the groups (P < .0001). Appearance, chewing, activity, appearance-donor site, and function-donor site were the domains that were most frequently chosen by the patients as the most important issues. Most of the patients rated their HR-QoL as somewhat better compared with their experience the month before they underwent reconstruction. The HR-QoL and overall quality of life (QoL) during the past 7 days were rated as very good in the FBG group and PBCMG group and good in the RP group and microvascular free flap group. CONCLUSIONS: HR-QoL of patients in the FBG and PBCMG groups did not differ significantly with regard to any of the domains, and these 2 groups consistently had the highest mean scores. Both groups differed significantly from the RP group, which tended to report the lowest mean scores for the domains.
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Mandíbula/cirurgia , Neoplasias Mandibulares/cirurgia , Procedimentos de Cirurgia Plástica/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Transplante Ósseo , Criança , Feminino , Retalhos de Tecido Biológico , Nível de Saúde , Humanos , Masculino , Doenças Mandibulares/cirurgia , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
Objective: Osteochondral defect presents a big challenge for clinical treatment. This study aimed at constructing a bi-layered composite chitosan/chitosan-ß-tricalcium phosphate (CS/CS-ß-TCP) scaffold and at repairing the rat osteochondral defect. Approach: The bi-layered CS/CS-ß-TCP scaffold was fabricated by lyophilization, and its microstructure was observed by a scanning electron microscope. Chondrocytes and bone marrow stem cells (BMSCs) were seeded into the CS layer and the CS-ß-TCP layer, respectively. Viability and proliferation ability of the cells were observed under a confocal microscope. After subcutaneous implantation, the chondrogenic ability of the CS layer and osteogenic ability of the CS-ß-TCP layer were evaluated by immunofluorescence. Then, the bi-layered scaffolds were implanted into the rat osteochondral defects and the harvested samples were macroscopically and histologically evaluated. Results: The bi-layered CS/CS-ß-TCP scaffold exhibited the distinctive microstructures for each layer. The seeded chondrocytes in the CS layer could maintain the chondrogenic lineage, whereas BMSCs in the CS-ß-TCP layer could continually differentiate into the osteogenic lineage. Moreover, cells in both layers could maintain well viability and excellent proliferation ability. For the in vivo study, the newly formed tissues in the bi-layered scaffolds group were similar with the native osteochondral tissues, which comprised hyaline-like cartilage and subchondral bone, with better repair effects compared with those of the pure CS group and the blank control group. Innovation: This is the first time that the bi-layered composite CS/CS-ß-TCP scaffold has been fabricated and evaluated with respect to osteochondral defect repair. Conclusion: The bi-layered CS/CS-ß-TCP scaffolds could facilitate osteochondral defect repair and might be the promising candidates for osteochondral tissue engineering.
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Quitosana/química , Fêmur/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Fêmur/patologia , Ratos , Projetos de PesquisaRESUMO
Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEV) have shown promising prospects as a cell-free strategy for bone tissue regeneration. Here, a bioactive MSCs-sEV-loaded electrospun silk fibroin/poly(ε-caprolactone) (SF/PCL) scaffold was synthesized via a mussel-inspired immobilization strategy assisted by polydopamine (pDA). This pDA modification endowed the as-prepared scaffold with high loading efficiency and sustained release profile of sEV. In addition, the fabricated composite scaffold exhibited good physiochemical, mechanical, and biocompatible properties. In vitro cellular experiments indicated that the MSCs-sEV-loaded composite scaffold promoted the adhesion and spreading of preosteoblast and endothelial cells, as well as enhanced osteogenic differentiation and angiogenic activity. In vivo experiments showed that the functionalized electrospun scaffolds promoted bone regeneration in a rat calvarial bone defect model. Results suggest that the developed MSCs-sEV-anchored pDA-modified SF/PCL electrospun scaffolds possess high application potential in bone tissue engineering owing to their powerful pro-angiogenic and -osteogenic capacities, cell-free bioactivity, and cost effectiveness.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Regeneração Óssea , Diferenciação Celular , Células Endoteliais , Indóis , Osteogênese , Polímeros , Ratos , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Searching for drug carries with controlled release and good biocompatibility has always been one of the research hotspots and difficulties. Herein, core-sheath nanofibrous mats (NFs) consisting of biocompatible poly(ethylene oxide) (PEO, core) and poly(l-lactic acid) (PLLA, sheath) for drug delivery were fabricated via coaxial electrospinning strategy. The nontoxic layered silicate rectorite (REC) with 0.5-1 wt % amount was introduced in the sheath for sustained drug delivery. Layered REC could be intercalated with PLLA macromolecule chains, leading to the densified structure for loading and keeping doxorubicin hydrochloride (DOX) while reversibly capturing and releasing DOX to delay the drug migration due to its high cation activity. The addition of REC in NFs could delay the initial burst release of DOX and prolong the residence time from 12 to 96 h. Moreover, DOX-loaded core-sheath NFs had in vitro culture with strong antitumor activity, which was confirmed by cytotoxicity results and live and dead assay. HepG2 tumor-bearing xenograft further demonstrated the tumor-suppression effect and the excellent safety of the DOX-loaded core-sheath NFs in vivo. The constructed NFs as drug carriers showed great potential in the local treatment of solid tumors.
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Nanofibras , Silicatos de Alumínio , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , MineraisRESUMO
Various materials are utilized as artificial substitutes for bone repair. In this study, a silk fibroin (SF) hydrogel reinforced by short silica nanoparticles (SiNPs)-distributed-silk fibroin nanofibers (SiNPs@NFs), which exhibits a superior osteoinductive property, is fabricated for treating bone defects. SF acts as the base part of the composite scaffold to mimic the extracellular matrix (ECM), which is the organic component of a native bone. The distribution of SiNPs clusters within the composite hydrogel partially mimics the distribution of mineral crystals within the ECM. Incorporation of SiNPs@NFs enhances the mechanical properties of the composite hydrogel. In addition, the composite hydrogel provides a biocompatible microenvironment for cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo studies confirm that the successful repair is achieved with the formation of a large amount of new bone in the large-sized cranial defects that are treated with the composite hydrogel. In conclusion, the SiNPs@NFs-reinforced-hydrogel fabricated in this study has the potential for use in bone tissue engineering.
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Fibroínas , Nanofibras , Nanopartículas , Biomimética , Hidrogéis , Osteogênese , Dióxido de Silício , Seda , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.