RESUMO
Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. In addition to improvements in bone delivery, potential regulation of bone development mechanisms involving receptor-regulated pathways has also been utilized. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems.
Assuntos
Sistemas de Liberação de Medicamentos , Humanos , Animais , Sistemas de Liberação de Medicamentos/métodos , Osso e Ossos/metabolismo , Doenças Ósseas/terapia , Desenvolvimento Ósseo/efeitos dos fármacos , Terapia Genética/métodosRESUMO
Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.
Assuntos
Vesículas Extracelulares , Células-Tronco , Vesículas Extracelulares/química , Humanos , Células-Tronco/citologia , Animais , Materiais Biocompatíveis/química , Doenças Ósseas/terapia , Regeneração Óssea , Transplante de Células-Tronco/métodos , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologiaRESUMO
The development of bone-targeting drug delivery systems holds immense promise for improving the treatment of skeletal diseases. By precisely delivering therapeutic agents to the affected areas of bone, these strategies can enhance drug efficacy, minimize off-target effects, and promote patient adherence, ultimately leading to improved treatment outcomes and an enhanced quality of life for patients. This review aims to provide an overview of the current state of affinity-based bone-targeting agents and recent breakthroughs in innovative bone-targeting adeno-associated virus (AAV) strategies to treat skeletal diseases in mice. In particular, this review will delve into advanced AAV engineering, including AAV serotype selection for bone targeting and capsid modifications for bone-specific tropism. Additionally, we will highlight recent advancements in AAV-mediated gene therapy for skeletal diseases and discuss challenges and future directions of this promising therapeutic approach.
Assuntos
Doenças Ósseas , Dependovirus , Sistemas de Liberação de Medicamentos , Terapia Genética , Vetores Genéticos , Dependovirus/genética , Humanos , Animais , Terapia Genética/métodos , Sistemas de Liberação de Medicamentos/métodos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Doenças Ósseas/terapia , Osso e Ossos/metabolismo , Técnicas de Transferência de Genes , CamundongosRESUMO
Despite advancements in medical care, the management of bone injuries remains one of the most significant challenges in the fields of medicine and sports medicine globally. Bone tissue damage is often associated with aging, reduced quality of life, and various conditions such as trauma, cancer, and infection. While bone tissue possesses the natural capacity for self-repair and regeneration, severe damage may render conventional treatments ineffective, and bone grafting may be limited due to secondary surgical procedures and potential disease transmission. In such cases, bone tissue engineering has emerged as a viable approach, utilizing cells, scaffolds, and growth factors to repair damaged bone tissue. This research shows a comprehensive review of the current literature on the most important and effective methods and materials for improving the treatment of these injuries. Commonly employed cell types include osteogenic cells, embryonic stem cells, and mesenchymal cells, while scaffolds play a crucial role in bone tissue regeneration. To create an effective bone scaffold, a thorough understanding of bone structure, material selection, and examination of scaffold fabrication techniques from inception to the present day is necessary. By gaining insights into these three key components, the ability to design and construct appropriate bone scaffolds can be achieved. Bone tissue engineering scaffolds are evaluated based on factors such as strength, porosity, cell adhesion, biocompatibility, and biodegradability. This article examines the diverse categories of bone scaffolds, the materials and techniques used in their fabrication, as well as the associated merits and drawbacks of these approaches. Furthermore, the review explores the utilization of various scaffold types in bone tissue engineering applications.
Assuntos
Traumatismos em Atletas , Doenças Ósseas , Osso e Ossos , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Humanos , Alicerces Teciduais/química , Doenças Ósseas/terapia , Osso e Ossos/lesões , Traumatismos em Atletas/terapia , Animais , Regeneração ÓsseaRESUMO
Adeno-associated viral (AAV) vectors have emerged as crucial tools in advancing gene therapy for skeletal diseases, offering the potential for sustained expression with low postinfection immunogenicity and pathogenicity. Preclinical studies support both the therapeutic efficacy and safety of these vectors, illustrating the promise of AAV-mediated gene therapy. Emerging technologies and innovations in AAV-mediated gene therapy strategies, such as gene addition, gene replacement, gene silencing, and gene editing, offer new approaches to clinical application. Recently, the increasing preclinical applications of AAV to rare skeletal diseases, such as fibrodysplasia ossificans progressiva (FOP) and osteogenesis imperfecta (OI), and prevalent bone diseases, such as osteoporosis, bone fracture, critical-sized bone defects, and osteoarthritis, have been reported. Despite existing limitations in clinical use, such as high cost and safety, the AAV-mediated gene transfer platform is a promising approach to deliver therapeutic gene(s) to the skeleton to treat skeletal disorders, including those otherwise intractable by other therapeutic approaches. This review provides a comprehensive overview of the therapeutic advancements, challenges, limitations, and solutions within AAV-based gene therapy for prevalent and rare skeletal diseases.
Assuntos
Doenças Ósseas , Dependovirus , Terapia Genética , Vetores Genéticos , Humanos , Dependovirus/genética , Terapia Genética/métodos , Vetores Genéticos/genética , Doenças Ósseas/terapia , Doenças Ósseas/genética , Animais , Técnicas de Transferência de Genes , Edição de Genes/métodosRESUMO
The number of patients with functional loss of bone and cartilage tissue has shown an increasing trend. Insufficient or inappropriate conventional treatments applied for trauma, orthopedic diseases, or other bone and cartilage-related disorders can lead to bone and cartilage damage. This represents a worldwide public health issue and a significant economic burden. Advanced therapeutic medicinal products (ATMPs) proposed promising alternative therapeutic modalities by application of cell-based and tissue engineering approaches. Recently, several ATMPs have been developed to promote bone and cartilage tissue regeneration. Fifteen ATMPs, two related to bone and 13 related to cartilage, have received regulatory approval and marketing authorization. However, four ATMPs were withdrawn from the market for various reasons. However, ATMPs that are still on the market have demonstrated positive results, their broad application faced limitations. The development and standardization of methodologies will be a major challenge in the coming decades. Currently, the number of ATMPs in clinical trials using mesenchymal stromal cells or chondrocytes indicates a growing recognition that current ATMPs can be improved. Research on bone and cartilage tissue regeneration continues to expand. Cell-based therapies are likely to be clinically supported by the new ATMPs, innovative fabrication processes, and enhanced surgical approaches. In this study, we highlighted the available ATMPs that have been used in bone and cartilage defects and discussed their advantages and disadvantages in clinical applications.
Assuntos
Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Animais , Doenças das Cartilagens/terapia , Doenças Ósseas/terapia , Cartilagem/lesões , Regeneração Óssea/efeitos dos fármacosRESUMO
Multiple myeloma (MM) is a clonal proliferative malignant tumor of plasma cells in bone marrow. With the aging of population in China, the incidence of MM is on the rise. Multiple myeloma bone disease (MBD) is one of the common clinical manifestations of MM, and 80%-90% of MM patients are accompanied by osteolytic lesions at the time of their first visit to the clinic. MBD not only increases the disability rate of patients, but also severely reduces the physical function of patients due to skeletal lesions and bone-related events. Currently available drugs for treating of MBD are ineffective and associated with side effects. Therefore, it is important to find new therapeutic approaches for the treatment of MBD. It is generally believed that the increased osteoclast activity and suppressed osteoblast function are the main pathologic mechanisms for MBD. However, more and more studies have suggested that soluble molecules in the bone marrow microenvironment, including cytokines, extracellular bodies, and metabolites, play an important role in the development of MBD. Therefore, exploring the occurrence and potential molecular mechanisms for MBD from multiple perspectives, and identifying the predictive biomarkers and potential therapeutic targets are of significance for the clinical treatment of MBD.
Assuntos
Doenças Ósseas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Doenças Ósseas/terapia , Osso e Ossos , Osteoclastos , Medula Óssea/patologia , Microambiente TumoralRESUMO
The extracellular matrixes (ECM), as well as the microenvironmental signals, play an essential role in osteogenesis by regulating intercellular pathways. Recently, it has been demonstrated that a newly identified RNA, circular RNA, contributes to the osteogenesis process. Circular RNA (circRNA), the most recently identified RNA, is involved in the regulation of gene expression at transcription to translation levels. The dysregulation of circRNAs has been observed in several tumors and diseases. Also, various studies have shown that circRNAs expression is changed during osteogenic differentiation of progenitor cells. Therefore, understanding the role of circRNAs in osteogenesis might help the diagnosis as well as treatment of bone diseases such as bone defects and osteoporosis. In this review, circRNA functions and the related pathways in osteogenesis have been discussed.
Assuntos
Osteogênese , RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Expressão Gênica , Diferenciação Celular , Transdução de Sinais , Doenças Ósseas/terapia , Engenharia Tecidual , Humanos , AnimaisRESUMO
Constitutional diseases of bone form a heterogeneous group of rare diseases of varied phenotypic presentations with a vast genetic heterogeneity. Detected mostly in childhood, they may also be diagnosed in adulthood. Medical history, clinical examination as well as biological and radiological investigations may lead to the diagnosis, which should be confirmed genetically. Joint limitations, early osteoarthritis, hip dysplasia, bone deformity, enthesopathies, bone fragility or a small height can be warning signs of a constitutional disease of bone. Establishing the diagnosis is crucial to enable optimal medical management with a specialized multidisciplinary team.
Les maladies osseuses constitutionnelles constituent un groupe hétérogène de maladies rares de présentations phénotypiques variées et d'une grande hétérogénéité génétique. Le plus souvent détectées dans l'enfance, elles peuvent également être diagnostiquées à l'âge adulte. L'anamnèse, l'examen clinique et les bilans biologiques et radiologiques permettent d'orienter le diagnostic, qui devra être confirmé par une analyse génétique. Les limitations articulaires, l'arthrose précoce, les dysplasies de hanches, les déformations osseuses, les enthésopathies ou la fragilité osseuse ainsi qu'une petite taille sont des signes d'alerte pour rechercher une maladie osseuse constitutionnelle. Établir le diagnostic est crucial pour permettre une prise en charge optimale, multidisciplinaire et spécialisée.
Assuntos
Doenças Ósseas , Luxação Congênita de Quadril , Osteoartrite , Humanos , Doenças Ósseas/diagnóstico , Doenças Ósseas/etiologia , Doenças Ósseas/terapia , Exame FísicoRESUMO
Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.
Assuntos
Doenças Ósseas , MicroRNAs , RNA Longo não Codificante , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diferenciação Celular/genética , Doenças Ósseas/genética , Doenças Ósseas/terapiaRESUMO
Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient "off-the-shelf" ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (~60%) within in vitro 3D model of MBD. Furthermore, NKs' post-thawing cytotoxic activity is significantly enhanced (~75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic "off-the-shelf" approach to improve the outcomes of patients suffering from MBD.
Assuntos
Doenças Ósseas , Mieloma Múltiplo , Animais , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Linhagem Celular Tumoral , Bortezomib/uso terapêutico , Imunoterapia , Doenças Ósseas/terapiaRESUMO
ABSTRACT Introduction: Hydrokinesitherapy is a rehabilitation method used for the treatment of different types of orthopedic, neurological, respiratory problems, etc. However, the existing literature presents not so much evidence regarding the greater efficacy of water treatment compared to dry treatment in patients with post-traumatic outcomes. Objective: Through the administration of a questionnaire, we tried to investigate the rehabilitation experience of hydrokinetic therapists (trained with the so-called Sequential and Preparatory Approach) in order to understand hydrokinesitherapy areas and methods of proper application based on experts' opinion. Methods: A cross-sectional study was carried out in 2020 by administering a questionnaire to physiotherapists trained in hydrokinesitherapy according to the Sequential and Preparatory Approach method, with the aim to investigate their opinion on the use of hydrokinesitherapy in patients with various orthopedic-traumatological problems. Microsoft FORMS® platform was used for the administration of the questionnaire. Results: Sixty-two users participated in the study. From their answers emerged that the use of hydrokinesitherapy is not recommended for the treatment of post-traumatic hypersensitization of peri-lesional tissues (hypersensitive scars; general hypersensitization) and neuropathic syndromes (of the upper and lower limbs). Conclusions: The data obtained from administering the questionnaire were not sufficient to create a specific path to define the appropriateness of hydrokinesitherapy for some orthopedic-traumatological problems but could be considered a good starting point on which to build future developments through further studies.
RESUMEN Introducción: La terapia hidrocinética es un método rehabilitador utilizado para el tratamiento de diferentes tipos de problemas ortopédicos, neurológicos, respiratorios, entre otros. Sin embargo, en la literatura existente no abundan evidencias en cuanto a la mayor eficacia del tratamiento con agua en comparación con el tratamiento seco en pacientes con resultados traumáticos. Objetivo: A través de un cuestionario, se intentó investigar la experiencia de rehabilitación de los terapeutas hidrocinéticos (entrenados con el llamado Enfoque Secuencial y Preparatorio) para comprender las áreas de la terapia hidrocinética y los métodos de aplicación adecuados con base en la opinión de expertos. Métodos: Se realizó un estudio transversal en el año 2020 mediante la administración de un cuestionario a fisioterapeutas formados en la terapia hidrocinética según el método de Abordaje Secuencial y Preparatorio, con el objetivo de averiguar su opinión sobre el uso de la terapia hidrocinética en pacientes con diversos problemas ortopédico-traumatológicos. Se utilizó la plataforma Microsoft FORMS® para la administración del cuestionario. Resultados: Sesenta y dos usuarios participaron en el estudio. De sus respuestas surgió que no se recomienda el uso de la terapia hidrocinética para el tratamiento de la hipersensibilización postraumática de los tejidos perilesionales (cicatrices hipersensibles; hipersensibilización general) y síndromes neuropáticos (de miembros superiores e inferiores). Conclusiones: Los datos obtenidos del cuestionario no fueron suficientes para crear una ruta específica que defina la idoneidad de la terapia hidrocinética para algunos problemas ortopédicos-traumatológicos, pero podría considerarse un buen punto de partida para construir futuros desarrollos a través de estudios adicionales.
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Humanos , Ferimentos e Lesões/terapia , Doenças Ósseas/terapia , Hidroterapia/métodos , Estudos TransversaisRESUMO
As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.
Assuntos
Doenças Ósseas , Células-Tronco Mesenquimais , Doenças Ósseas/genética , Doenças Ósseas/terapia , Células da Medula Óssea , Regeneração Óssea/genética , Diferenciação Celular/genética , Epigênese Genética , Humanos , OsteogêneseRESUMO
Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/ß-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD.
Assuntos
Doenças Ósseas , Mieloma Múltiplo , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Doenças Ósseas/terapia , Difosfonatos/uso terapêutico , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Microambiente Tumoral , Via de Sinalização WntRESUMO
OBJECTIVES/HYPOTHESIS: The increasing use of cross-sectional imaging has led to the predicament of incidental mastoid opacification (IMO). We investigated the prevalence of IMO and the clinical need for ENT assessment or intervention when identified. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The PRISMA statement standards were used to search electronic databases including Medline, Embase, PubMed, and Web of Science. The selection criteria were mastoid opacification found on computed tomography (CT) or magnetic resonance imaging (MRI) as incidental findings. RESULTS: A total of 16 studies were identified for qualitative analysis and 15 for quantitative analysis, mainly retrospective. The pooled prevalence of IMO in 246,288 patients was 8.4% (95% CI 5.5-12.0). The prevalence of IMO was significantly higher in studies with children (17.2%, 95% CI 10.9-24.6) than those with adults (6.1%, 95% CI 3.3-9.6); smaller sample size studies (12.4%, 95% CI 8.1-17.3) compared to larger sample size studies (4.1%, 95% CI 1.5-7.8); and when IMO was detected by viewing images (14.5%, 95% CI 9.9-19.8) compared to reading reports (3.5%, 95% CI 1.3-6.6). Imaging modality was not a significant moderator due to similar IMO rate on CT (8.6%, 95% CI 1.8-19.7) and MRI (10.4%, 95% CI 4.9-17.6). Nine studies reported on clinical outcomes of patients with IMO, and none reliably reported any cases of clinical mastoiditis. CONCLUSIONS: The term "mastoiditis" on radiology reports based on IMO does not indicate a clinical diagnosis of mastoiditis, although the current body of evidence is limited. Otolaryngology review is suggested if clinical correlation detects otological signs or symptoms. LEVEL OF EVIDENCE: NA Laryngoscope, 132:422-432, 2022.
Assuntos
Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/epidemiologia , Imageamento por Ressonância Magnética , Processo Mastoide , Tomografia Computadorizada por Raios X , Doenças Ósseas/terapia , Humanos , Achados Incidentais , Prevalência , Estudos RetrospectivosRESUMO
Reconstruction of bone due to surgical removal or disease-related bony defects is a clinical challenge. It is known that the immune system exerts positive immunomodulatory effects on tissue repair and regeneration. In this study, we evaluated the in vivo efficacy of autologous neutrophils on bone regeneration using a rabbit calvarial defect model. Methods: Twelve rabbits, each with two surgically created calvarial bone defects (10 mm diameter), were randomly divided into two groups; (i) single application of neutrophils (SA-NP) vs. SA-NP control, and (ii) repetitive application of neutrophils (RA-NP) vs. RA-NP control. The animals were euthanized at 4 and 8 weeks post-operatively and the treatment outcomes were evaluated by micro-computed tomography, histology, and histomorphometric analyses. Results: The micro-CT analysis showed a significantly higher bone volume fraction (bone volume/total volume) in the neutrophil-treated groups, i.e., median interquartile range (IQR) SA-NP (18) and RA-NP (24), compared with the untreated controls, i.e., SA-NP (7) and RA-NP (14) at 4 weeks (p < 0.05). Similarly, new bone area fraction (bone area/total area) was significantly higher in neutrophil-treated groups at 4 weeks (p < 0.05). Both SA-NP and RA-NP had a considerably higher bone volume and bone area at 8 weeks, although the difference was not statistically significant. In addition, immunohistochemical analysis at 8 weeks revealed a higher expression of osteocalcin in both SA-NP and RA-NP groups. Conclusions: The present study provides first hand evidence that autologous neutrophils may have a positive effect on promoting new bone formation. Future studies should be performed with a larger sample size in non-human primate models. If proven feasible, this new promising strategy could bring clinical benefits for bone defects to the field of oral and maxillofacial surgery.
Assuntos
Regeneração Óssea , Neutrófilos/metabolismo , Crânio/fisiologia , Animais , Doenças Ósseas/terapia , Modelos Animais de Doenças , Masculino , Neutrófilos/transplante , Osteocalcina/metabolismo , Coelhos , Crânio/diagnóstico por imagem , Crânio/patologia , Microtomografia por Raio-XRESUMO
Background: To evaluate hyperbaric oxygen therapy (HBOT) on infection rates and repair rates during the treatment of large jaw cysts. Methods: A prospective randomized, non-blinded, controlled clinical trial included 90 patients with jaw cysts, randomly divided into three groups. Patients were treated with enucleations and bone substitute was used in the experimental and control groups. The experimental group received HBOT. The primary predictor variable was HBOT. The infection rate, repair rate, preoperative volume of the jaw cysts, age, and sex were statistically analyzed. The Fisher exact test was used to compare the infection rate and postoperative complications. The repair rate of the bone defects was analyzed using the repeated-measures analysis of variance and the least significant difference tests. The Kendall's coefficient of concordance and Kappa statistics were calculated to evaluate the consistency between the two investigators. Results: The infection rate was 3.4% in the experimental group, 14.3% in the blank group, and 32.1% in the control group (P<0.05). The repair rate in the experimental group was significantly higher than in the control and blank groups at 1, 3 and 6 months after surgery (P<0.05). Conclusion: The results showed that HBOT reduced the postoperative infection rate following the enucleation of large jaw cysts with bone substitute filling, and it also improved the bone repair rate.
Assuntos
Oxigenoterapia Hiperbárica/métodos , Cistos Maxilomandibulares/terapia , Adolescente , Adulto , Idoso , Doenças Ósseas/complicações , Doenças Ósseas/terapia , Regeneração Óssea/fisiologia , Substitutos Ósseos/uso terapêutico , China , Feminino , Humanos , Infecções/complicações , Infecções/terapia , Cistos Maxilomandibulares/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different diseases. Mesenchymal stem/stromal cells (MSCs) and their secretome-including extracellular vesicles (EVs) are of great interest, due to their role in tissue regeneration, immunomodulatory capacity and low immunogenicity. So far, clinical studies are not very conclusive as they show conflicting efficacies regarding the use of MSCs. An additional process possibly involved in regeneration might be cell fusion. This process occurs in both a physiological and a pathophysiological context and can be affected by immune response due to inflammation. In this review the role of MSCs and cell fusion in tissue regeneration is discussed.