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The anterolateral thigh (ALT) free flap has become a workhorse for head and neck reconstruction. This paper offers a thorough introduction to the ALT flap, covering its anatomy, surgical technique, adaptable designs, and use in a range of clinical settings along with case studies. With its long vascular pedicle and tissue versatility, the ALT flap is well-suited for matching varied defects. Still, understanding possible anatomic variances and managing complications are critical to its success. With this paper as a comprehensive guidance, surgeons can apply the ALT flap for difficult head and neck reconstructions and achieve the best possible results.
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Chemotherapy is one of the main treatments for oral squamous cell carcinoma (OSCC), especially as a combined modality approach with and after surgery or radiotherapy. Limited therapeutic efficiency and serious side effects greatly restrict the clinical performance of chemotherapeutic drugs. The development of smart nanomedicines has provided new research directions, to some extent. However, the involvement of complex carrier compositions inevitably brings biosafety concerns and greatly limits the "bench-to-bed" translation of most nanomedicines reported. In this study, a carrier-free self-assembled prodrug was fabricated by two triterpenes (glycyrrhetinic acid, GA and ginsenoside Rh2, Rh2) isolated from medicinal plants, licorice, and ginseng, for the targeted and highly effective treatment of OSCC. Reactive oxygen species (ROS) self-supplied molecule TK-GA2 was synthesized with ROS-responsive thioketal linker and prodrug was prepared by a rapid-solvent-exchange method with TK-GA2 and Rh2. After administration, oral tumor cells transported large amounts of prodrugs with glucose ligands competitively. Endogenous ROS in oral tumor cells then promoted the release of GA and Rh2. GA further evoked the generation of a large number of ROS to help self-boosted drug release and increase oxidative stress, synergistically causing tumor cell apoptosis with Rh2. Overall, this carrier-free triterpene-based prodrug might provide a preeminent opinion on the design of effective chemotherapeutics with low systemic toxicity against OSCC.
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Carcinoma de Células Escamosas , Liberación de Fármacos , Neoplasias de la Boca , Profármacos , Especies Reactivas de Oxígeno , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Especies Reactivas de Oxígeno/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Ginsenósidos/química , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Animales , Triterpenos/química , Triterpenos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacología , Ratones , Apoptosis/efectos de los fármacosRESUMEN
The aim of this study was to conduct a comprehensive review of the predictive significance of PNI in HNSCC survival outcomes. A systematic search was conducted across multiple databases, and all studies published in the last decade were screened (Research Registry ID: reviewregistry1853). The included studies were assessed using the Quality in Prognosis Studies tool. Survival outcome data were extracted, combined, and presented as hazard ratios (HR) with a 95% confidence interval (CI). Totally, 74 studies encompassing 27,559 patients were analyzed and revealed a cumulative occurrent rate of 30% for PNI in HNSCC. PNI+ HNSCC patients had a worse overall survival (HR: 1.91, 95% CI: 1.71-2.13), disease-specific survival (HR: 1.79, 95% CI: 1.55-2.07), disease-free survival (HR: 1.82, 95% CI: 1.69-1.96), local recurrence (HR: 2.54, 95% CI: 1.93-3.33), locoregional recurrence (HR: 2.27, 95% CI: 1.82-2.82), locoregional relapse free survival (HR: 1.77, 95% CI: 1.28-2.45), distant metastasis (HR: 1.82, 95% CI: 1.34-2.48), and distant metastasis-free survival (HR: 2.97, 95% CI: 1.82-4.85) compared to those PNI- patients. The available evidence unequivocally establishes PNI as a critical prognostic factor for worse survival in HNSCC patients.
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OBJECTIVES: The aim of this superiority trial was to investigate the clinical outcomes of arthrocentesis as an early treatment supported by use of an occlusal splint vs use of an occlusal splint only in the management of temporomandibular joint (TMJ) arthralgia. METHODS: Ninety-five adults presenting with TMJ arthralgia were recruited into the study and randomised into 2 groups: Group 1 received arthrocentesis as an early treatment supported by use of an occlusal splint, whereas group 2 received treatment with an occlusal splint only. Seventy-four patients (group 1: n = 37; group 2: n = 37) completed the 1-year follow-up schedule and were included in the final analysis. Reduction of pain intensity measured by a numeric rating scale and increase in mouth opening distance (unassisted maximal, assisted maximal, and pain-free) was seen in both treatment groups. RESULTS: In group 1, pain intensity significantly decreased at 6 weeks and all subsequent time points compared with group 2. In terms of mouth opening distance, a significant improvement was observed in both groups during the course of treatment, but statistical significance was not seen between the 2 treatment groups. CONCLUSIONS: Early arthrocentesis supported by use of an occlusal splint is superior to use of an occlusal splint alone in the treatment of TMJ arthralgia. Arthrocentesis with occlusal splint support could be discussed as first-line treatment for arthralgia of the TMJ, which may co-occur with various painful and nonpainful conditions of TMJ disorders.
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Skeletal Class III malocclusion is one type of dentofacial deformity that significantly affects patients' facial aesthetics and oral health. The orthodontic treatment of skeletal Class III malocclusion presents challenges due to uncertainties surrounding mandibular growth patterns and treatment outcomes. In recent years, disease-specific radiographic features have garnered interest from researchers in various fields including orthodontics, for their exceptional performance in enhancing diagnostic precision and treatment effect predictability. The aim of this narrative review is to provide an overview of the valuable radiographic features in the diagnosis and management of skeletal Class III malocclusion. Based on the existing literature, a series of analyses on lateral cephalograms have been concluded to identify the significant variables related to facial type classification, growth prediction, and decision-making for tooth extractions and orthognathic surgery in patients with skeletal Class III malocclusion. Furthermore, we summarize the parameters regarding the inter-maxillary relationship, as well as different anatomical structures including the maxilla, mandible, craniofacial base, and soft tissues from conventional and machine learning statistical models. Several distinct radiographic features for Class III malocclusion have also been preliminarily observed using cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI).
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OBJECTIVES: Microvascular bone flap jaw reconstruction has achieved satisfactory clinical outcomes. However, little is known about the long-term stability of the reconstructed jaw. This prospective longitudinal study aimed to investigate the long-term stability of jaw reconstruction and factors that were associated with it. METHODS: Patients with successful computer-assisted osseous free-flap jaw reconstruction in the Department of Oral and Maxillofacial Surgery, Queen Mary Hospital, Hong Kong were recruited for this prospective longitudinal study. The three-dimensional jaw models at the pre-operative plan, post-operative 1-month, and 2 years were aligned and compared. RESULTS: A total of 69 patients were recruited, among which 48 patients were available for the long-term analysis. Compared to 1-month after surgery, further deviation from the pre-operative plan was observed at post-operative 2 years. Lack of accuracy in surgery, segmental mandible resection especially with the involvement of mandible angles, and post-operative radiation therapy were identified as the significant factors affecting the positional stability of the reconstructed jaw (p < 0.05). Stable reconstruction was observed in the subgroup analysis of patients without post-operative radiation therapy. CONCLUSION: Up to the best of our knowledge, this is the first prospective longitudinal study reporting the long-term stability of jaw reconstruction and its affecting factors. Our data demonstrated that the reconstructed jaw position lacked stability over the postoperative period. How to improve long-term stability of reconstructed jaw thus optimize the functional outcomes warrants further studies.
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Procedimientos de Cirugía Plástica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Longitudinales , Estudios Prospectivos , Procedimientos de Cirugía Plástica/métodos , Anciano , Adulto , Colgajos Quirúrgicos , Maxilares , Reconstrucción Mandibular/métodosRESUMEN
PROteolysis TArgeting Chimeras (PROTACs), as a recently identified technique in the field of new drug development, provide new concepts for disease treatment and are expected to revolutionize drug discovery. With high specificity and flexibility, PROTACs serve as an innovative research tool to target and degrade disease-relevant proteins that are not currently pharmaceutically vulnerable to eliminating their functions by hijacking the ubiquitin-proteasome system. To date, PROTACs still face the challenges of low solubility, poor permeability, off-target effects, and metabolic instability. The combination of nanotechnology and PROTACs has been explored to enhance the in vivo performance of PROTACs regarding overcoming these challenging hurdles. In this review, we summarize the latest advancements in the building-block design of PROTAC prodrug nanoparticles and provide an overview of existing/potential delivery systems and loading approaches for PROTAC drugs. Furthermore, we discuss the current status and prospects of the split-and-mix approach for PROTAC drug optimization. Additionally, the advantages and translational potentials of carrier-free nano-PROTACs and their combinational therapeutic effects are highlighted. This review aims to foster a deeper understanding of this rapidly evolving field and facilitate the progress of nano-PROTACs that will continue to push the boundaries of achieving selectivity and controlled release of PROTAC drugs.
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Complejo de la Endopetidasa Proteasomal , Quimera Dirigida a la Proteólisis , Proteolisis , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas/metabolismo , Descubrimiento de Drogas/métodosRESUMEN
PURPOSE: Intratumoral nerve infiltration relates to tumor progression and poor survival in oral squamous cell carcinoma (OSCC). How neural involvement regulates antitumor immunity has not been well characterized. This study aims to investigate molecular mechanisms of regulating tumor aggressiveness and impairing antitumor immunity by nerve-derived factors. EXPERIMENTAL DESIGN: We performed the surgical lingual denervation in an immunocompetent mouse OSCC model to investigate its effect on tumor growth and the efficacy of anti-PD-1 immunotherapy. A trigeminal ganglion neuron and OSCC cell coculture system was established to investigate the proliferation, migration, and invasion of tumor cells and the PD-L1 expression. Both the neuron-tumor cell coculture in vitro model and the OSCC animal model were explored. RESULTS: Lingual denervation slowed down tumor growth and improved the efficacy of anti-PD-1 treatment in the OSCC model. Coculturing with neurons not only enhanced the proliferation, migration, and invasion but also upregulated TGFß-SMAD2 signaling and PD-L1 expression of tumor cells. Treatment with the TGFß signaling inhibitor galunisertib reversed nerve-derived tumor aggressiveness and downregulated PD-L1 on tumor cells. Similarly, lingual denervation in vivo decreased TGFß and PD-L1 expression and increased CD8+ T-cell infiltration and the expression of IFNγ and TNFα within tumor. CONCLUSIONS: Neural involvement enhanced tumor aggressiveness through upregulating TGFß signaling and PD-L1 expression in OSCC, while denervation of OSCC inhibited tumor growth, downregulated TGFß signaling, enhanced activities of CD8+ T cells, and improved the efficacy of anti-PD-1 immunotherapy. This study will encourage further research focusing on denervation as a potential adjuvant therapeutic approach in OSCC. SIGNIFICANCE: This study revealed the specific mechanisms for nerve-derived cancer progression and impaired antitumor immunity in OSCC, providing a novel insight into the cancer-neuron-immune network as well as pointing the way for new strategies targeting nerve-cancer cross-talk as a potential adjuvant therapeutic approach for OSCC.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Animales , Ratones , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/terapia , Desnervación , Inmunoterapia , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/terapia , Factor de Crecimiento Transformador beta/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Positive bone margins have been shown to be associated with worse locoregional control and survival performance in oral oncology patients. With the application of computer-assisted surgery and patient-specific surgical guides, the authors can accurately execute the preoperative osteotomy plan. However, how well the authors can predict the margin distance in the final histopathology with a preoperative computed tomography (CT) scan, the factors associated with it, and how much leeway CT should spare when designing the osteotomy planes during virtual surgical planning (VSP) remain to be investigated. MATERIALS AND METHODS: Patients from January 2021 to December 2022 with benign or malignant jaw tumors and with signs of bone marrow involvement in the preoperative CT scan in our center were prospectively recruited to the study. VSP and measurement of the closest margin distance in the CT scan were performed by the single team of surgeons. The resection specimen was processed, and the margin distances were measured by a dedicated senior pathologist with the knowledge of orientation of the osteotomy planes. RESULTS: A total of 35 patients were recruited, with 21 malignant and 14 benign cases. Sixty-eight bone margins were quantitatively analyzed. No significant difference in margin distances measured from the CT scan and final histopathology was detected ( P =0.19), and there was a strong correlation between the two (r s =0.74, P <0.01). A considerable amount of variance was detected in the level of discrepancy between margin distances measured in the CT scan and final histopathology (overall SD=6.26 mm, malignancy SD=7.44 mm, benign SD=4.40 mm). No significant correlation existed between the two margin distances when only maxilla tumor margins were assessed ( P =0.16). CONCLUSION: The bone margin distance in VSP is reliably correlated to the final pathological margin distance. A leeway distance of 15mm and 9mm should be considered when designing the osteotomy planes for malignancy and benign cases, respectively. Extra attention should be paid to maxilla cases when predetermining the osteotomy planes during VSP.
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Neoplasias , Cirugía Asistida por Computador , Humanos , Estudios Prospectivos , Márgenes de Escisión , Osteotomía/métodos , Tomografía Computarizada por Rayos X , Cirugía Asistida por Computador/métodosRESUMEN
Oral potentially malignant disorders (OPMDs) are mucosal conditions with an inherent disposition to develop oral squamous cell carcinoma. Surgical management is the most preferred strategy to prevent malignant transformation in OPMDs, and surgical approaches to treatment include conventional scalpel excision, laser surgery, cryotherapy, and photodynamic therapy. However, in reality, since all patients with OPMDs will not develop oral squamous cell carcinoma in their lifetime, there is a need to stratify patients according to their risk of malignant transformation to streamline surgical intervention for patients with the highest risks. Artificial intelligence (AI) has the potential to integrate disparate factors influencing malignant transformation for robust, precise, and personalized cancer risk stratification of OPMD patients than current methods to determine the need for surgical resection, excision, or re-excision. Therefore, this article overviews existing AI models and tools, presents a clinical implementation pathway, and discusses necessary refinements to aid the clinical application of AI-based platforms for cancer risk stratification of OPMDs in surgical practice.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Lesiones Precancerosas , Humanos , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/etiología , Neoplasias de la Boca/cirugía , Carcinoma de Células Escamosas/patología , Inteligencia Artificial , Carcinoma de Células Escamosas de Cabeza y Cuello , Lesiones Precancerosas/patología , Medición de RiesgoRESUMEN
Salivary biomarkers can improve the efficacy, efficiency, and timeliness of oral and maxillofacial disease diagnosis and monitoring. Oral and maxillofacial conditions in which salivary biomarkers have been utilized for disease-related outcomes include periodontal diseases, dental caries, oral cancer, temporomandibular joint dysfunction, and salivary gland diseases. However, given the equivocal accuracy of salivary biomarkers during validation, incorporating contemporary analytical techniques for biomarker selection and operationalization from the abundant multi-omics data available may help improve biomarker performance. Artificial intelligence represents one such advanced approach that may optimize the potential of salivary biomarkers to diagnose and manage oral and maxillofacial diseases. Therefore, this review summarized the role and current application of techniques based on artificial intelligence for salivary biomarker discovery and validation in oral and maxillofacial diseases.
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Caries Dental , Enfermedades de la Boca , Enfermedades Periodontales , Humanos , Inteligencia Artificial , Enfermedades de la Boca/diagnóstico , Biomarcadores , Enfermedades Periodontales/diagnósticoRESUMEN
OBJECTIVES: This study assessed the validity of nomograms for predicting malignant transformation (MT) among patients with oral leukoplakia (OL) and oral lichen planus (OLP). MATERIALS AND METHODS: Two nomograms were identified following a systematic search. Variables to interrogate both nomograms were obtained for a retrospective OL/OLP cohort. Then, the nomograms were applied to estimate MT probabilities twice and their average was used to calculate the discriminatory performance, calibration, and potential net benefit of the models. Subgroup analyses were performed for patients with OL, OLP, and oral epithelial dysplasia. RESULTS: Predicted probabilities were mostly significantly higher among OL/OLP patients who developed MT compared to those who did not (p = <0.001-0.034). AUC values and Brier scores of the nomograms were 0.644-0.844 and 0.040-0.088 among OL patients and 0.580-0.743 and 0.008-0.072 among OLP patients. Decision curve analysis suggested that the nomograms had some net benefit for risk stratification. However, the models did not best binary dysplasia grading in discriminatory validity and net benefit among patients with OL and oral epithelial dysplasia. CONCLUSION: Nomograms for predicting MT may have satisfactory validity among patients with OL than OLP, but they do not outperform binary dysplasia grading in risk stratification of OL.
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The prevalence of oral squamous cell carcinoma (OSCC) has increased in recent decades, and its impact on the health system has become a new aspect [...].
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Antimicrobial peptides (AMPs) are a developing class of natural and synthetic oligopeptides with host defense mechanisms against a broad spectrum of microorganisms. With in-depth research on the structural conformations of AMPs, synthesis or modification of peptides has shown great potential in effectively obtaining new therapeutic agents with improved physicochemical and biological properties. Notably, AMPs with self-assembled properties have gradually become a hot research topic for various biomedical applications. Compared to monomeric peptides, these peptides can exist in diverse forms (e.g., nanoparticles, nanorods, and nanofibers) and possess several advantages, such as high stability, good biocompatibility, and potent biological functions, after forming aggregates under specific conditions. In particular, the stability and antibacterial property of these AMPs can be modulated by rationally regulating the peptide sequences to promote self-assembly, leading to the reconstruction of molecular structure and spatial orientation while introducing some peptide fragments into the scaffolds. In this work, four self-assembled AMPs are developed, and the relationship between their chemical structures and antibacterial activity is explored extensively through different experiments. Importantly, the evaluation of antibacterial performance in both in vitro and in vivo studies has provided a general guide for using self-assembled AMPs in subsequent treatments for combating bacterial infections.
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Péptidos Antimicrobianos , Nanofibras , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Antibacterianos/farmacología , Antibacterianos/química , OligopéptidosAsunto(s)
Peroné , Colgajos Quirúrgicos , Humanos , Peroné/cirugía , Mandíbula/cirugía , Trasplante ÓseoRESUMEN
OBJECTIVES: Oncologic risk is a serious concern of submental artery island flaps. Here, we introduce the contralateral-based submental artery island flap (C-SAIF) and demonstrate its feasibility and long-term oncological safety in reconstructing oral cancer-related defects. METHODS: An anatomical study was performed concentrating on the pedicle length in seven cadavers. Then, a retrospective study was carried out on C-SAIF patients operated on by a single team. The standard surgical technique of C-SAIF was conducted. Outcomes including operative time, length of hospital stay, volume of intraoperative blood loss, and scores of the Multidisciplinary Salivary Gland Society (MSGS) questionnaire were compared with a similar cohort reconstructed with anterolateral thigh free flap (ALTF). In addition, oncological outcomes were evaluated by the 5-year cumulative survival rate between C-SAIF and ALTF patients. RESULTS: The pedicle length of C-SAIF was sufficient for the flap to be extended to the contralateral oral cavity. Fifty-two patients were included in the retrospective study, and nineteen of them underwent reconstruction with C-SAIF. The operative time of C-SAIF was shorter (p = 0.003), and the intraoperative blood loss was less (p = 0.004) than that of ALTF. There was no difference in MSGS scores. The results of survival analysis revealed comparable survival curves for the two groups in terms of overall survival, disease-specific survival, and disease-free survival. CONCLUSION: C-SAIF is a feasible and reliable flap for reconstructing oral cancer-related defects. Moreover, it is an effective island flap to preserve the perforator and pedicle without compromising oncological safety.
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Colgajos Tisulares Libres , Neoplasias de la Boca , Procedimientos de Cirugía Plástica , Humanos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Estudios de Factibilidad , Neoplasias de la Boca/cirugía , Arterias/cirugíaRESUMEN
Salivary adenoid cystic carcinoma (SACC) is a rare malignant tumor of the salivary gland. Studies have suggested that miRNA may play a crucial role in the invasion and metastasis of SACC. This study aimed to investigate the role of miR-200b-5p in SACC progression. Reverse transcription-quantitative PCR and western blot assay were used to detect the expression levels of miR-200b-5p and BTBD1. The biological functions of miR-200b-5p were evaluated via wound-healing assays, transwell assays, and xenograft nude mice model. The interaction between miR-200b-5p and BTBD1 was assessed using luciferase assay. Results showed that miR-200b-5p was downregulated in the SACC tissues while BTBD1 was upregulated. miR-200b-5p overexpression suppressed SACC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatics prediction and luciferase reporter assay revealed that miR-200b-5p could directly bind to BTBD1. Besides, miR-200b-5p overexpression could rescue the tumor-promoting effect of BTBD1. miR-200b-5p inhibited tumor progression by modulating EMT-related proteins, targeting BTBD1 and inhibiting PI3K/AKT signaling pathway. Overall, our findings indicate that miR-200b-5p can suppress SACC proliferation, migration, invasion, and EMT by regulating BTBD1 and PI3K/AKT axis, providing a promising therapeutic target for SACC treatment.
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Carcinoma Adenoide Quístico , MicroARNs , Neoplasias de las Glándulas Salivales , Animales , Ratones , Humanos , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Invasividad Neoplásica/genética , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Exosomes, small extracellular vesicles that function as a key regulator of cell-to-cell communication, are emerging as a promising candidate for bone regeneration. Here, we aimed to investigate the effect of exosomes from pre-differentiated human alveolar bone-derived bone marrow mesenchymal stromal cells (AB-BMSCs) carrying specific microRNAs on bone regeneration. Exosomes secreted from AB-BMSCs pre-differentiated for 0 and 7 days were cocultured with BMSCs in vitro to investigate their effect on the differentiation of the BMSCs. MiRNAs from AB-BMSCs at different stages of osteogenic differentiation were analyzed. BMSCs seeded on poly-L-lactic acid(PLLA) scaffolds were treated with miRNA antagonist-decorated exosomes to verify their effect on new bone regeneration. Exosomes pre-differentiated for 7 days effectively promoted the differentiation of BMSCs. Bioinformatic analysis revealed that miRNAs within the exosomes were differentially expressed, including the upregulation of osteogenic miRNAs (miR-3182, miR-1468) and downregulation of anti-osteogenic miRNAs (miR-182-5p, miR-335-3p, miR-382-5p), causing activation of the PI3K/Akt signaling pathway. The treatment of BMSC-seeded scaffolds with anti-miR-182-5p decorated exosomes demonstrated enhanced osteogenic differentiation and efficient formation of new bone. In conclusion, Osteogenic exosomes secreted from pre-differentiated AB-BMSCs were identified and the gene modification of exosomes provides great potential as a bone regeneration strategy. DATA AVAILABILITY STATEMENT: Data generated or analyzed in this paper partly are available in the GEO public data repository(http://www.ncbi.nlm.nih.gov/geo).