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In recent years, enterovirus A71 (EV-A71) infection has become a major global public health problem, especially for infants and young children. The results of epidemiological research show that EV-A71 infection can cause acute hand, foot, and mouth disease (HFMD) and complications of the nervous system in severe cases, including aseptic pediatric meningoencephalitis, acute flaccid paralysis, and even death. Many studies have demonstrated that EV-A71 infection may trigger a variety of intercellular and intracellular signaling pathways, which are interconnected to form a network that leads to the innate immune response, immune escape, inflammation, and apoptosis in the host. This article aims to provide an overview of the possible mechanisms underlying infection, signaling pathway activation, the immune response, immune evasion, apoptosis, and the inflammatory response caused by EV-A71 infection and an overview of potential therapeutic strategies against EV-A71 infection to better understand the pathogenesis of EV-A71 and to aid in the development of antiviral drugs and vaccines.
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Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Lactente , Criança , Humanos , Pré-Escolar , Doença de Mão, Pé e Boca/terapia , Imunidade Inata , Inflamação , Enterovirus Humano A/genéticaRESUMO
PURPOSE: This study aims to evaluate the efficacy of single pararectus approach in patients confirmed with acetabular fracture involving anterior and posterior columns. METHODS: A total of 58 patients confirmed with acetabular fracture involving anterior and posterior columns and treated at our hospital between January 2015 and January 2020 were retrospectively analyzed. A single pararectus approach was applied for all patients. Routine X-rays were performed at follow-up of one, three, six, 12, and 18 months, and three-dimensional CT scans were added at six and 18 months. Fracture reduction quality was assessed using the Matta score system, and functional assessment used the Modified Merle D'Aubigné and Postel score system. Post-operative complications, including fat liquefaction and deep vein thrombosis, were recorded and analyzed. RESULTS: The median operation time was 186 min while the intra-operative blood loss was 421 mL. The rate of good-to-excellent reduction was 94.8%, and the rate of good-to-excellent hip function score reached 93.1%. Seven patients presented with post-operative complications, including three intra-operative small vascular injuries, two peritoneal small perforations, one fat liquefaction, and one deep vein thrombosis. CONCLUSION: Using a single pararectus approach is convenient and effective for treating acetabular fracture involving anterior and posterior columns, especially those involving the quadrilateral area. TRIAL REGISTRATION: ChiCTR, ChiCTR2100054604. Registered 21 December 2022. Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=144783 .
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Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Trombose Venosa , Humanos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Acetábulo/lesões , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. RESULTS: Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. CONCLUSIONS: Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.
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Fator 2 de Crescimento de Fibroblastos/farmacologia , Hidrogéis/química , Estruturas Metalorgânicas/química , Pele/patologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Força Compressiva , Cobre/química , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Hidrogéis/farmacologia , Camundongos , Niacina/química , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologiaRESUMO
BACKGROUND: Denis and Ferguson et al.'s three-column spinal theory has been widely accepted and applied. However, this three-column theory was proposed based solely on observation and experience without thorough documented data and analysis. The aim of this study was to analyze and improve Denis and Ferguson et al.'s three-column spinal theory to propose a novel three-column concept in epidemiology, morphology and biomechanics. METHODS: A retrospective analysis of the computed tomography imaging data of patients with a diagnosis of T11-L5 vertebral fractures was conducted between February 2010 and December 2018. Three-dimensional (3D) distribution maps of fracture lines of all subjects were obtained based on 3D mapping techniques. In addition, a 25-year-old health male volunteer was recruited for the vertebral finite element force analysis. RESULTS: The present study enrolled 459 patients (age: 48 ± 11.42 years), containing a total of 521 fractured vertebrae. The fracture lines peaked in the upper and the outer third sections of the vertebra, starting from the anterior part of the vertebral pedicles in 3-D maps. Regarding flexion and extension of the spine, the last third of the vertebral body in front of the spinal canal was one main stress center in the finite element analysis. The stress on the vertebral body was greater in front of the pedicles in the lateral bending. CONCLUSION: The study reveals that the posterior one-third of the vertebral body in front of the spinal canal and the posterior one-third of the vertebral body in front of the pedicle are very different in terms of fracture characteristics and risks to spinal canal (3D maps and stress distributing graphs), therefore, they should be classified as different columns. We provide strong evidence that Su's three-column theory complies with the characteristics of vertebral physiological structure, vertebral fracture, and vertebral biomechanics.
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Fraturas da Coluna Vertebral , Vértebras Torácicas , Adulto , Fixação Interna de Fraturas , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesõesRESUMO
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with highly aggressive behavior and early systemic metastasis. The survival rates for osteosarcoma remain unchanged over the past two decades. Studies aiming to find new or alternative therapies for patients with refractory osteosarcoma are urgently needed. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging clinical activity in NSLCC and soft tissue sarcoma, whereas its effect on osteosarcoma has not been studied. In our study, we investigated the anti-tumor activity and underlying mechanism of anlotinib in osteosarcoma. Various in vitro and in vivo models of human osteosarcoma were used to determine the anti-proliferative, anti-angiogenesis and anti-metastasis efficacy of anlotinib. Our results showed that anlotinib suppressed tumor growth and increased the chemo-sensitivity of osteosarcoma. In addition, anlotinib inhibited migration and invasion in osteosarcoma cells. Furthermore, in order to explore the anti-tumor mechanism of anlotinib, phospho-RTK antibody arrays were performed. These analyses confirmed that anlotinib suppressed the phosphorylation of MET, VEGFR2 and the downstream signaling pathway activation. Moreover, we demonstrated that anlotinib blocked hepatocyte growth factor (HGF)-induced cell migration, invasion and VEGF-induced angiogenesis. Notably, a 143B-Luc orthotopic osteosarcoma model further showed that anlotinib significantly inhibited growth and lung metastasis of implanted tumor cells. Our preclinical work indicates that anlotinib acts as a novel inhibitor of VEGFR2 and MET that blocks tumorigenesis in osteosarcoma, which could be translated into future clinical trials.
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Neoplasias Ósseas/tratamento farmacológico , Indóis/farmacologia , Osteossarcoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Quinolinas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/farmacologia , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Osteossarcoma/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A (RA) is an active oleanane-type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose- and time-dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species (ROS) generation and JNK and ERK1/2 activation. Apoptosis induction was evaluated by the activation of caspase-3, caspase-8, and caspase-9 and poly-ADP ribose polymerase (PARP) cleavage. RA-induced cell death was significantly restored by the ROS scavenger glutathione (GSH), the pharmacological inhibitor of JNK SP600125, or specific JNK knockdown by shRNA. Additionally, signal transducer and activator of transcription 3 (STAT3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH, SP600125, and JNK-shRNA. Further investigation showed that STAT3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK/c-Jun and STAT3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.
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Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Saponinas/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Osteossarcoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Fatores de Tempo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To examine the role of store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca2+ contributes to the regulation of osteosarcoma cells. METHODS: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) activity by luciferase assays. RESULTS: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca2+ channels involved down-regulation of NFATc1 in osteosarcoma cells. CONCLUSIONS: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca2+ entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.
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Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. The abilities of chemotherapy resistance are major roadblock in the successful treatment of OS. The clarification of mechanism regarding cell survival during OS chemotherapy are important. Here, we examined HER4 expression by immunohistochemistry in a large series of OS tissues, and found HER4 expression correlated with tumor characteristics and patient survival rates. HER4 knockdown by shRNA inhibited OS cell growth and tumorigenesis, and induced cell senescence and apoptosis in vitro and in vivo. We demonstrated that HER4 expression upregulated in the adverse conditions, such as serum starvation and sphere culture. Moreover, HER4 knockdown cells became more sensitive in stressful conditions such as loss of attachment, cytotoxic agents or nutrition insufficiency. Mechanism studies revealed that HER4 interacted with NDRG1, and NDRG1 overexpression could antagonize HER4 knockdown-mediated cell growth and apoptosis in stressed conditions. There was a positive correlation between HER4 and NDRG1 immunoreactivity in OS patients. Together, our present study shows that HER4 and/or NDRG1 might play a critical role for the cell survival and chemo-resistance of OS, and could be used as potential therapeutic targets in OS.
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Neoplasias Ósseas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Osteossarcoma/metabolismo , Receptor ErbB-4/metabolismo , Animais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Proteínas de Ciclo Celular/genética , Sobrevivência Celular , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/patologia , Receptor ErbB-4/genéticaRESUMO
In vivo mineralization is a multistep process involving mineral-protein complexes and various metastable compounds in vertebrates. In this complex process, the minerals produced in the mitochondrial matrix play a critical role in initiating extracellular mineralization. However, the functional mechanisms of the mitochondrial minerals are still a mystery. Herein, an in vitro enzymatic reaction strategy is reported for the generation of biomimic amorphous calcium phosphate (EACP) nanominerals by an alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) in a weakly alkalescent aqueous condition (pH 8.0-8.5), which is partially similar to the mitochondrial environment. Significantly, the EACP nanomineral obviously promotes autophagy and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by activating an AMPK related pathway, and displays a high performance in promoting bone regeneration. These results provide in vitro evidence for the effect of ATP on the formation and stabilization of the mineral in the mineralization process, demonstrating a potential strategy for the preparation of the biomimic mineral for treating bone related diseases.
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Biomimética/métodos , Fosfatase Alcalina/metabolismo , Autofagia/fisiologia , Fosfatos de Cálcio/química , Diferenciação Celular/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/fisiologiaRESUMO
Osteosarcoma (OS) is the most frequent primary malignant bone tumour. Alternol, a novel compound purified from microbial fermentation products exerts anti-tumour effects across several cancer types. The effect of alternol on human OS remains to be elucidated. We first evaluated the anti-tumour effect of alternol in several human OS cell lines in vitro and investigated its underlying mechanism. Alternol inhibited OS cell proliferation, migration and induced caspase-dependent apoptosis, G2/M cell cycle arrest in a dose and time-dependent manner. Moreover, alternol treatment inhibited signal transducer and activator of transcription-3 (STAT3) phosphorylation in 143B and MG63 human OS cells, as evaluated using a STAT3-dependent dual luciferase reporter system. Exposure to alternol resulted in excessive reactive oxygen species (ROS) generation and Jun amino-terminal kinases (JNK), extracellular signal-regulated kinases (ERK1/2) and p38 activation. Furthermore, alternol-induced cell death was significantly restored in the presence of the ROS scavenger, N-acetyl-l-cysteine (NAC) or a caspase inhibitor Z-VAD-FMK. NAC also prevented G2/M phase arrest and phosphorylation of mitogen-activated protein kinases (MAPK), but did not reverse STAT3 inactivation. Finally, alternol suppressed tumour growth in vivo in the nude mouse OS tibia orthotopic model. Immunohistochemistry revealed that alternol treatment resulted in down-regulation of phosph-STAT3 Tyr705 and up-regulation of cleaved caspase-3 and phosph-SAPK (Stress-activated protein kinases)/JNK expression. Taken together, our results reveal that alternol suppresses cell proliferation, migration and induces apoptosis, cell cycle arrest by modulating of ROS-dependent MAPK and STAT3 signalling pathways in human OS cells. Therefore, alternol is a promising candidate for developing anti-tumour drugs target OS.
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Antineoplásicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Sistema de Sinalização das MAP Quinases , Osteossarcoma/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Produtos Biológicos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Osteossarcoma/enzimologia , Osteossarcoma/patologia , Fatores de TempoRESUMO
BACKGROUND During total hip arthroplasty (THA) drainage is used by most surgeons. However, the optimal drainage strategy remains controversial. The aim of this prospective cohort study was to determine the safety and efficacy of a four-hour drainage clamping technique in patients undergoing THA. MATERIAL AND METHODS There were 64 patients who underwent THA from March 2012 to December 2015 who were enrolled in the study; 32 patients were randomly assigned to four hours of a drainage clamping technique (clamping group); 32 patients were treated with a non-clamping drainage technique (non-clamping group). All perioperative clinical details were recorded for comparative analysis. RESULTS The postoperative drainage volume and calculated blood loss were significantly greater in the drainage non-clamping group, p<0.001 and p=0.028, respectively. Significantly more patients in the drainage non-clamping group required a blood transfusion, seven cases versus one case (p=0.023). Significantly more units of blood were transfused in the drainage non-clamping group (p=0.001). No significant differences were found for all other clinical outcome factors. CONCLUSIONS The four-hour drainage clamping technique following THA, compared with drainage non-clamping technique reduced blood loss and requirement for blood transfusion. There was no increase in adverse clinical events using the four-hour drainage clamping method. Therefore, four-hour drainage clamping has the potential for routine use in THA.
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Artroplastia de Quadril/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Drenagem , Instrumentos Cirúrgicos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: Generalized muscle weakness is the primary characteristic of sarcopenia. Handgrip strength (HGS) is widely employed to detect muscle weakness. However, knee extension strength (KES) declines much earlier and more pronounced than HGS, and there is a stronger correlation between KES and functional performance. Therefore, KES may be a more appropriate proxy for identifying muscle weakness compared to HGS. The purpose of this review was to clarify the KES measurement towards a standardized approach and summarize the cut-off points for KES. METHODS: A literature search was conducted in Web of Science, PubMed, Elsevier, Scopus and Medline databased up to July 10th, 2023. RESULTS: A total of 12 articles were ultimately included in this review, which proposed various cut-off points for KES. Notably, these studies exhibited high heterogeneities, including diverse living settings for participants, KES measurement, methods for KES normalization, methodologies for determining cut-off points and study designs. CONCLUSIONS: No consensus on cut-off points for KES was reached due to the heterogeneities in KES measurement and normalized methods among studies. To enhance the comparability among studies and facilitate the sarcopenia screening framework, a standardized approach for KES measurement and KES normalization are needed. Regarding KES measurement, the hand-held dynamometer-based isometric KES is easy to access and ideally suited for both clinical and community settings, while isokinetic KES, representing the gold standard, is preferred for research settings. Additionally, it is suggested to normalize isometric KES to body weight (BW), while normalizing isokinetic KES to allometrically scaled BW.
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The limited regulation strategies of the regeneration microenvironment significantly hinder bone defect repair effectiveness. One potential solution is using biomaterials capable of releasing bioactive ions and biomolecules. However, most existing biomaterials lack real-time control features, failing to meet high regulation requirements. Herein, a new Strontium (Sr) and epigallocatechin-3-gallate (EGCG) based metal-phenolic network with polydopamine (PMPNs) modification is prepared. This material reinforces a biomimetic scaffold made of extracellular matrix (ECM) and hydroxyapatite nanowires (nHAW). The PMPNs@ECM/nHAW scaffold demonstrates exceptional scavenging of free radicals and reactive oxygen species (ROS), promoting HUVECs cell migration and angiogenesis, inducing stem cell osteogenic differentiation, and displaying high biocompatibility. Additionally, the PMPNs exhibit excellent photothermal properties, further enhancing the scaffold's bioactivities. In vivo studies confirm that PMPNs@ECM/nHAW with near-infrared (NIR) stimulation significantly promotes angiogenesis and osteogenesis, effectively regulating the microenvironment and facilitating bone tissue repair. This research not only provides a biomimetic scaffold for bone regeneration but also introduces a novel strategy for designing advanced biomaterials. The combination of real-time photothermal intervention and long-term chemical intervention, achieved through the release of bioactive molecules/ions, represents a promising direction for future biomaterial development.
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Regeneração Óssea , Catequina , Matriz Extracelular , Células Endoteliais da Veia Umbilical Humana , Indóis , Osteogênese , Alicerces Teciduais , Regeneração Óssea/efeitos dos fármacos , Humanos , Alicerces Teciduais/química , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Osteogênese/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Animais , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Polímeros/química , Durapatita/química , Durapatita/farmacologia , Estrôncio/química , Estrôncio/farmacologia , Nanofios/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Diferenciação Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Movimento Celular/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Electrical stimulation can effectively accelerate bone healing. However, the substantial size and weight of electrical stimulation devices result in reduced patient benefits and compliance. It remains a challenge to establish a flexible and lightweight implantable microelectronic stimulator for bone regeneration. Here, we use self-powered technology to develop an electric pulse stimulator without circuits and batteries, which removes the problems of weight, volume, and necessary rigid packaging. The fully implantable bone defect electrical stimulation (BD-ES) system combines a hybrid tribo/piezoelectric nanogenerator to provide biphasic electric pulses in response to rehabilitation exercise with a conductive bioactive hydrogel. BD-ES can enhance multiple osteogenesis-related biological processes, including calcium ion import and osteogenic differentiation. In a rat model of critical-sized femoral defects, the bone defect was reversed by electrical stimulation therapy with BD-ES and subsequent bone mineralization, and the femur completely healed within 6 weeks. This work is expected to advance the development of symbiotic electrical stimulation therapy devices without batteries and circuits.
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Regeneração Óssea , Osteogênese , Humanos , Animais , Ratos , Terapia por Exercício , Calcificação Fisiológica , Estimulação ElétricaRESUMO
Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.
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Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications.
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Background: Recently, a locking plate (LP) combined with a suture button was applied for distal clavicle Neer type IIb fractures. However, to our knowledge, there is limited information on clinical outcomes surrounding locking plates combined with a suture button in the treatment of Neer type IIb distal clavicle fractures. The aim of this study was to compare the outcomes among three different fixation techniques for the treatment of Neer type IIb distal clavicle fractures. Methods: We performed a retrospective cohort study of 53 patients with Neer type IIb distal clavicle fractures who were treated with a hook plate (HP group, 16 patients), a locking plate alone (LP group, 18 patients), or a locking plate with a suture button (LPSB group, 19 patients) in our hospital between March 2014 and August 2019. The clinical and radiological outcomes were evaluated, including union time, postoperative complications, and function of the shoulder joint. Results: The follow-up period was at least 2 years for all patients. All patients in the LPSB group achieved bone healing at the final follow-up. No significant differences were observed, including age, sex, side, time to surgery, duration of surgery, and mean follow-up period among the three groups (p > 0.05). The union time was shorter in the LPSB group than in the other two groups (p < 0.05). Postoperative complications were lower in the LPSB group than in the other two groups (p < 0.05). The visual analog scale score and Constant-Murley score in the LPSB group were better than those in the other groups at 3 and 6 months postoperatively (p < 0.05). Conclusion: Compared with HP and LP alone, LPSB yields better clinical outcomes and lower complication rates in the treatment of Neer type IIb distal clavicle fractures.
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Objective: To evaluate the effectiveness of TiRobot-assisted surgery by O-arm navigation system for percutaneous minimally invasive treatment of posterior pelvic ring injury. Methods: The clinical data of 76 patients with posterior pelvic ring injury between January 2016 and June 2021 were retrospectively analyzed. Among them, 45 cases were treated with minimally invasive percutaneous sacroiliac screw fixation assisted by TiRobot and O-arm navigation system (study group), 31 cases were treated with minimally invasive percutaneous sacroiliac screw fixation under the guidance of C-arm X-ray machine (control group). There was no significant difference in gender, age, cause of injury, Tile classification, time from injury to operation between the two groups ( P>0.05). The operation time, intraoperative blood loss, the times of nail track adjustment, and intraoperative fluoroscopy times were recorded. The quality of fracture reduction was evaluated by Matta score. At last follow-up, Majeed score was used to evaluate the recovery of pelvic function. Results: A total of 72 screws were implanted in the study group, with a median of 1 (1, 2) screws per patient. In the control group, 47 screws were implanted, with a median of 1 (1, 2) screws per patient. There was no significant difference in the number of screws between the two groups ( Z=-0.392, P=0.695). The operation time, intraoperative blood loss, times of nail track adjustment, and intraoperative fluoroscopy times in the study group were significantly less than those in the control group ( P<0.05). All patients were followed up 6-24 months (mean, 14 months). No serious complications was found after operation and during follow-up. Matta score was used to evaluate the quality of fracture reduction at 1 week after operation, and there was no significant difference between the two groups ( Z=-1.135, P=0.256). At last follow-up, there was no significant difference of Majeed score between the two groups ( Z=-1.279, P=0.201). Conclusion: TiRobot-assisted surgery by O-arm navigation system is a reliable surgical method for the treatment of posterior pelvic ring injury, which can reduce the operation time and fluoroscopy times when compared with the traditional operation under the guidance of C-arm X-ray machine. The safety, accuracy, and efficiency of the operation were improved.
Assuntos
Fraturas Ósseas , Ossos Pélvicos , Cirurgia Assistida por Computador , Perda Sanguínea Cirúrgica , Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Humanos , Imageamento Tridimensional , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient's families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair.
RESUMO
Background: Osteoid osteoma is a common benign bone tumor, and clinically there is severe local pain that typically worsens at night. The conventional CT-guided radiofrequency ablation (RFA) was widely used in the treatment of osteoid osteoma (OO), which could result in some radiation-related and imprecise complications due to the overdose of radiation exposure. This study aimed to compare the surgical effect of robot-assisted RFA with O-arm navigation and conventional CT-guided RFA in the treatment of OO. Methods: Sixty-two patients who underwent robot-assisted RFA with O-arm navigation (Robot-RFA, n = 24) or CT-guided RFA (CT-RFA, n = 38) were included in this retrospective cohort study. The mean follow-up time was 23.3 months. The intra-operative data, primary technical success rate, visual analog scale (VAS), and post-operative complications were analyzed. Results: Primary technical success was obtained in 23 patients who had robot-assisted RFA, and 35 patients who had conventional CT-guided RFA. One patient in Robot-RFA group and three patients in CT-RFA group with pain recurrence received repeat-RFA and had a secondary success. Mean operation time and dose of radiation exposure were lower in Robot-RFA group than that in CT-RFA group. The Robot-RFA group took fewer K-wire adjustment times for each patient than the CT-RFA group. There was a statistically significant difference in the mean operation time, dose of radiation exposure, and K-wire adjustment times between the groups (p < 0.05). No complications associated with the procedure were reported in the two groups during the follow-up period. Conclusion: Robot-assisted RFA with O-arm navigation is a safer and more precise strategy in the treatment of osteoid osteoma with less operation time and radiation exposure compared with the conventional CT-guided radiofrequency ablation.