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Regenerative Biomaterials 2024Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM)....
Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM). Unfortunately, current treatment approaches for OM are not satisfactory. To address this issue, this study focuses on the development and evaluation of an injectable magnesium oxide (MgO) nanoparticle (NP)-coordinated phosphocreatine-grafted chitosan hydrogel (CMPMg-VCM) loaded with varying amounts of vancomycin (VCM) for the treatment of OM. The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel, and the MgO-incorporated hydrogel exhibits anti-swelling properties. The release of VCM from the hydrogel effectively kills bacteria, with CMPMg-VCM (50) showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days. Importantly, all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation. Furthermore, experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth, while also protecting the infected bone from osteolysis. These beneficial properties are attributed to the burst release of VCM, which disrupts bacterial biofilm, as well as the release of Mg ions and hydroxyl by the degradation of MgO NPs, which inhibits bacterial growth and prevents osteolysis. Overall, the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.
PubMed: 38919844
DOI: 10.1093/rb/rbae049 -
RSC Advances Jun 2024In a previous study, we found that oligodeoxynucleotide (ODN) YW002 could induce the activity of alkaline phosphatase of early osteogenesis in human periodontal membrane...
PURPOSE
In a previous study, we found that oligodeoxynucleotide (ODN) YW002 could induce the activity of alkaline phosphatase of early osteogenesis in human periodontal membrane stem cells, and downregulate the synthesis of nitric oxide in RAW 264.7 cells in the late inflammatory stage, laying the experimental foundation for the subsequent application of ODN YW002 in periodontitis. However, free ODN does not easily adhere to cells and is easily hydrolyzed by nuclease, so the immune effect of ODN is greatly reduced. Therefore, the nano-drug delivery system provides a method for efficient delivery and uptake of ODN.
METHODS
We synthesized a polyethyleneimine (PEI) modified chondroitin sulfate (CS) derivative (PEI-CS) Michael addition to deliver ODN YW002. We aimed to evaluate whether PEI-CS could effectively deliver YW002 to RAW 264.7 cells and if it can regulate inflammation . PEI-CS/YW002 nanocomplexes were locally injected into a mouse periodontitis model, and the therapeutic effects were evaluated by microcomputed tomography (micro-CT) and hematoxylin-eosin (H&E) staining.
RESULTS
The results indicated that PEI-CS had good biocompatibility and could form a stable nanocomplex with YW002 at a mass ratio of 4 : 1. Moreover, PEI-CS could deliver YW002 into RAW 246.7 cells and markedly decreased the expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Histological evaluation and micro-CT scanning showed that PEI-CS/YW002 nanocomplexes effectively inhibited periodontitis and reduced alveolar bone resorption in mice.
CONCLUSION
Our study has underscored the potential of PEI-CS/YW002 nanocomplexes as promising agents for the prevention and treatment of periodontitis due to their potent anti-inflammatory effects.
PubMed: 38919285
DOI: 10.1039/d4ra00884g -
Journal of Nanobiotechnology Jun 2024Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability,...
Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.
Topics: Animals; Calcium Phosphates; Bone Cements; Mice; Swine; Calcitonin Gene-Related Peptide; Osteogenesis; Swine, Miniature; Bone Regeneration; Spine; Ganglia, Spinal; Cell Line; Magnesium
PubMed: 38918787
DOI: 10.1186/s12951-024-02595-1 -
Scientific Reports Jun 2024Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a...
Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. On a per-cell basis, encapsulation in microporous hydrogel induced a 4 × increase in alkaline phosphatase (ALP) activity and calcium mineral deposition in comparison to nonporous hydrogel, as measured by ALP and calcium assays, which indicates more robust osteogenic differentiation. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.
Topics: Mesenchymal Stem Cells; Osteogenesis; Humans; Hydrogels; Cell Differentiation; Porosity; Alkaline Phosphatase; Cells, Cultured; Cell Encapsulation; Mesenchymal Stem Cell Transplantation; Injections
PubMed: 38918510
DOI: 10.1038/s41598-024-65731-9 -
International Journal of Biomaterials 2024Periodontitis therapy employing nanomaterials with submicron sizes holds promise for enhancing osteogenesis and facilitating periodontal cell proliferation. This study...
INTRODUCTION
Periodontitis therapy employing nanomaterials with submicron sizes holds promise for enhancing osteogenesis and facilitating periodontal cell proliferation. This study aims to assess the potential of nanoparticle-based rice husk liquid smoke (-RHLS) in an animal model of periodontitis by evaluating the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-k (RANK), and receptor activator of nuclear factor-k ligand (RANKL).
METHODS
Twenty-eight male Wistar rats were inoculated with 10 CFU/ml of in the sulcus mandibular incisor region to create periodontitis and subsequently treated with n-RHLS while the control with saline. Immunohistochemical staining was performed on the mandibular incisor to assess OPG, RANK, and RANKL expression 2 and 7 days after treatment.
RESULTS
OPG expression exhibited a significant increase at both 2 and 7 days, while RANKL expression decreased notably after 7 days of treatment using n-RHLS ( < 0.05). In contrast, RANK expression did not show significant differences compared to the control groups ( > 0.05).
CONCLUSION
Nanostructured liquid smoke derived from rice husk nanoparticles (-RHLS) demonstrates potential as a therapeutic agent for periodontitis, especially on OPG/RANK/RANKL expression, by modulating OPG and RANKL expression to support periodontal tissue health.
PubMed: 38912518
DOI: 10.1155/2024/5015893 -
Heliyon Jun 2024Dental follicle cells (DFCs) promote bone regeneration and Circular RNAs (circRNAs) play crucial roles in bone development and regeneration. Our previous study...
Dental follicle cells (DFCs) promote bone regeneration and Circular RNAs (circRNAs) play crucial roles in bone development and regeneration. Our previous study demonstrated the upregulation of circFgfr2 expression during the osteogenic differentiation of DFCs. However, the molecular mechanisms and functional roles of circFgfr2 in DFCs osteogenesis remain unclear. In this study, we aimed to investigate the subcellular localization of circFgfr2 in DFCs using fluorescence hybridization. investigations demonstrated that circFgfr2 overexpression promoted osteogenic differentiation, as evidenced by real-time quantitative polymerase chain reaction. By integrating the outcomes of bioinformatics analyses, dual luciferase reporter experiments, and chromatin isolation by RNA purification, we identified circFgfr2 as a sponge for miR-133a-3p, a key regulator of osteogenic differentiation. Moreover, miR-133a-3p suppressed osteogenic differentiation by targeting DLX3 and RUNX2 in DFCs. We validated that circFgfr2 promoted the osteogenic differentiation of DFCs through the miR-133a-3p/DLX3 axis. To further investigate the therapeutic potential of circFgfr2 in bone regeneration, we conducted experiments and histological analyses. Overall, these results confirmed the crucial role of circFgfr2 in promoting osteogenesis. In summary, our findings demonstrated that the circFgfr2/miR-133a-3p/DLX3 pathway acts as a cascade, thereby identifying circFgfr2 as a promising molecular target for bone tissue engineering.
PubMed: 38912473
DOI: 10.1016/j.heliyon.2024.e32498 -
Cureus May 2024Temporomandibular joint (TMJ) ankylosis results in malocclusion, poor feeding, difficulty in maintaining oral hygiene, and facial esthetic deformity. The basic surgical...
Temporomandibular joint (TMJ) ankylosis results in malocclusion, poor feeding, difficulty in maintaining oral hygiene, and facial esthetic deformity. The basic surgical objectives in the treatment of TMJ ankylosis are to establish joint movement, prevent relapse, and achieve normal growth and development. Here, we present an operated case ofsurgical correction of mandibular hypoplasia; however, the patient came back after three years due to unsatisfactory results and underwent bilateral coronoidectomy and gap arthroplasty. Bones were osteotomized at the LeFort I level and the maxillary segment was down-fractured and mobilized to bring into occlusion with the mandible. In the present case, the lower pharyngeal airway changed from 5 mm pre-treatment to 10 mm post-treatment, and the facial angle was changed from 73 to 84 post-treatment. Assessment of the pharyngeal airway is done with a high suspicion of obstructive sleep apnea and facial deformity is mandatory in the management of TMJ ankylosis.
PubMed: 38910750
DOI: 10.7759/cureus.60857 -
Cureus May 2024Temporomandibular joint (TMJ) ankylosis is generally characterised by a complex aetiology, with several contributing causes, including infections, autoimmune diseases,...
Temporomandibular joint (TMJ) ankylosis is generally characterised by a complex aetiology, with several contributing causes, including infections, autoimmune diseases, trauma, and congenital anomalies. This case report describes a three-year-old female suffering from traumatic temporomandibular ankylosis with retrognathia, severe mouth-opening restriction, and obstructive sleep apnea (OSA). The present case highlights the difficulties with TMJ ankylosis, especially when access to healthcare is sought out late and delayed diagnosis is prevalent. Mandibular distraction osteogenesis and awake fiberoptic intubation were used in the surgical and anaesthetic management of this case, with the otorhinolaryngology team on standby to perform a tracheostomy if required, highlighting the necessity of a multidisciplinary approach in such cases. Patients with TMJ ankylosis have significant life-altering changes, including psychological stress, chewing difficulty, speech difficulties, facial distortion, and speech impediment. When OSA progresses, it also presents more health risks. For the purpose of treating TMJ ankylosis, avoiding serious problems, and enhancing patient well-being, prompt diagnosis and therapy are crucial. In order to optimise patient results, this case study highlights the need for knowledge and research in the treatment of TMJ ankylosis as well as the requirement of medical professionals working together in a synergistic way.
PubMed: 38910731
DOI: 10.7759/cureus.60828 -
Cureus May 2024Osteogenesis imperfecta (OI) is a rare inherited skeletal disease, characterized by bone fragility and low bone density. There are several types of OI, varying in...
Osteogenesis imperfecta (OI) is a rare inherited skeletal disease, characterized by bone fragility and low bone density. There are several types of OI, varying in severity from benign to severe. We report a case of type II OI, which is a lethal form according to the Sillence classification. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. The genetic analysis was done along with genetic counseling. Death occurred on day nine of life due to respiratory failure secondary to pulmonary hypoplasia.
PubMed: 38910652
DOI: 10.7759/cureus.60945 -
Journal of Zhejiang University.... Jun 2024Osteoarthritis (OA) is a chronic progressive osteoarthropathy in the elderly. Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in...
Osteoarthritis (OA) is a chronic progressive osteoarthropathy in the elderly. Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA. However, the specific mechanism of osteoclast differentiation in OA remains unclear. In our study, gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus (GEO) repository. GEO2R and Funrich analysis tools were employed to find differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that chemical carcinogenesis, reactive oxygen species (ROS), and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone. Furthermore, fourteen DEGs that are associated with oxidative stress were identified. The first ranked differential gene, heme oxygenase 1 (), was selected for further validation. Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of . Carnosol was revealed to inhibit osteoclastogenesis by targeting and upregulating the expression of antioxidant protein in vitro. Meanwhile, carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo. Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA. Targeting in subchondral osteoclasts may offer novel insights for the treatment of early OA.
Topics: Heme Oxygenase-1; Osteoarthritis; Osteoclasts; Humans; Animals; Oxidative Stress; Cell Differentiation; Osteogenesis; Male; Mice; Reactive Oxygen Species
PubMed: 38910496
DOI: 10.1631/jzus.B2300303