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Biomedical Materials (Bristol, England) Jun 2024Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological...
Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological fracture. Gallium (Ga) ion possesses antineoplastic and anti-bone resorption properties, suggesting the potential for its local administration to impede the growth of metastatic bone lesions. This study investigated the chemotherapeutic potential, cytotoxicity, and osteogenic effects of a Ga-doped glass polyalkenoate cement (GPC) (C-TA2) compared to its non-gallium (C-TA0) counterpart. Ion release profiles revealed a biphasic pattern characterized by an initial burst followed by a gradually declining release of ions. C-TA2 continued to release Ga steadily throughout the experimentation period (7 days) and exhibited prolonged zinc (Zn) release compared to C-TA0. Interestingly, the Zn release from both GPCs appeared to cause a chemotherapeutic effect against H1092 lung cancer cells in vitro, with the prolonged Zn release from C-TA2 extending this effect. Unfortunately, both GPCs enhanced the viability of HCC2218 breast cancer cells, suggesting that the chemotherapeutic effects of Zn could be tied to cellular differences in preferred Zn concentrations. The utilization of SAOS-2 and MC3T3 cell lines as bone cell models yielded conflicting results, with the substantial decline in MC3T3 viability closely associated with silicon (Si) release, indicating cellular variations in Si toxicity. Despite this ambiguity, both GPCs exhibited harmful effects on the osteogenesis of primary rat osteoblasts, raising concerns about excessive burst Zn release. While Ga/Zn-doped GPCs hold promise for treating metastatic bone lesions caused by lung cancers, further optimization is required to mitigate cytotoxicity on healthy bone.
PubMed: 38917820
DOI: 10.1088/1748-605X/ad5ba5 -
ACS Applied Bio Materials Jun 2024The present work aims to develop optimized scaffolds for bone repair by incorporating mesoporous nanoparticles into them, thereby combining bioactive factors for cell...
Stimuli-Responsive Codelivery System-Embedded Polymeric Nanofibers with Synergistic Effects of Growth Factors and Low-Intensity Pulsed Ultrasound to Enhance Osteogenesis Properties.
The present work aims to develop optimized scaffolds for bone repair by incorporating mesoporous nanoparticles into them, thereby combining bioactive factors for cell growth and preventing rapid release or loss of effectiveness. We synthesized biocompatible and biodegradable scaffolds designed for the controlled codelivery of curcumin (CUR) and recombinant human bone morphogenic protein-2 (rhBMP-2). Active agents in dendritic silica/titania mesoporous nanoparticles (DSTNs) were incorporated at different weight percentages (0, 2, 5, 7, 9, and 10 wt %) into a matrix of polycaprolactone (PCL) and polyethylene glycol (PEG) nanofibers, forming the CUR-BMP-2@DSTNs/PCL-PEG delivery system (S0, S2, S5, S7, S9, and S10, respectively, with the number showing the weight percentage). To enhance the formation process, the system was treated using low-intensity pulsed ultrasound (LIPUS). Different advanced methods were employed to assess the physical, chemical, and mechanical characteristics of the fabricated scaffolds, all confirming that incorporating the nanoparticles improves their mechanical and structural properties. Their hydrophilicity increased by approximately 25%, leading to ca. 53% enhancement in their water absorption capacity. Furthermore, we observed a sustained release of approximately 97% for CUR and 70% for BMP-2 for the S7 (scaffold with 7 wt % DSTNs) over 28 days, which was further enhanced using ultrasound. In vitro studies demonstrated accelerated scaffold biodegradation, with the highest level observed in S7 scaffolds, approximately three times higher than the control group. Moreover, the cell viability and proliferation on DSTNs-containing scaffolds increased when compared to the control group. Overall, our study presents a promising nanocomposite scaffold design with notable improvements in structural, mechanical, and biological properties compared to the control group, along with controlled and sustained drug release capabilities. This makes the scaffold a compelling candidate for advanced bone tissue engineering and regenerative therapies.
PubMed: 38917363
DOI: 10.1021/acsabm.4c00111 -
Environmental Research Jun 2024Due to the persistent nature and significant negative impacts of perfluorooctanoic acid (PFOA) on human health and other organisms, the emergence of new PFOA...
Due to the persistent nature and significant negative impacts of perfluorooctanoic acid (PFOA) on human health and other organisms, the emergence of new PFOA alternatives, such as perfluoro (2-methyl-3-oxhexanoic) acid (GenX) and perfluoro-3,6,9-trioxyundecanoic acid (PFO3TDA), have drawn significant attention. However, the toxic effects of PFOA and its substitutes on bones remain limited. In this study, we administered different concentrations of PFOA, GenX, and PFO3TDA via gavage to 3-week-old male BALB/C mice for four weeks. X-ray and micro-CT scans revealed shortening of the femur and tibia and significant reduction in bone density. Additionally, PFOA, GenX, and PFO3TDA promoted osteoblast senescence and impaired osteogenic capabilities. This was characterized by a decrease in the expression of osteogenesis-related genes (OCN, ALP, Runx2, etc.) and an increase in the expression of aging and inflammation-related factors (p16, P21, MMP3, etc). Furthermore, RNA sequencing revealed activation of the ferroptosis pathway in PFOA-treated osteoblasts, characterized by notable lipid peroxidation and excessive iron accumulation. Finally, by inhibiting the ferroptosis pathway with ferrostatin-1 (Fer-1), we effectively alleviated the senescence of MC3T3-E1 cells treated with PFOA, GenX, and PFO3TDA, and improved their osteogenic capabilities. Therefore, our study provides a new therapeutic insight into the impact of PFOA and its substitutes on bone growth and development.
PubMed: 38914254
DOI: 10.1016/j.envres.2024.119483 -
Toxicology Letters Jun 2024Increasing epidemiological evidence has shown that PM exposure is significantly associated with the occurrence of osteoporosis. It has been well demonstrated that PM...
Increasing epidemiological evidence has shown that PM exposure is significantly associated with the occurrence of osteoporosis. It has been well demonstrated that PM exposure enhanced the differentiation and function of osteoclasts by indirectly causing chronic inflammation, while the mechanism in osteoblasts remains unclear. In our study, toxic effects were evaluated by direct exposure of 20-80μg/ml PM to MC3T3-E1 cells and BMSCs. The results showed that PM exposure did not affect cell viability via proliferation and apoptosis, but significantly inhibited osteoblast differentiation in a dose-dependent manner. Osteogenic transcription factors Runx2 and Sp7 and other biomarkers Alp and Ocn decreased after PM exposure. RNA-seq revealed TGF-β signaling was involved in PM exposure inhibited osteoblast differentiation, which led to P-Smad1/5 and P-Smad2 reduction in the nucleus by increasing the ubiquitination and degradation of Smad4. At last, the inflammation response increased in MC3T3-E1 cells with PM exposure. Moreover, the mRNA levels of Mmp9 increased in bone marrow-derived macrophage cells treated with the conditional medium collected from MC3T3-E1 cells exposed to PM. Overall, these results indicated that PM exposure inhibits osteoblast differentiation and concurrently increases the maturation of osteoclasts. Our study provides in-depth mechanistic insights into the direct impact of PM exposure on osteoblast, which would indicate the unrecognized role of PM on osteoporosis.
PubMed: 38914176
DOI: 10.1016/j.toxlet.2024.06.010 -
Nanoscale Jun 2024Polyetheretherketone (PEEK), renowned for its exceptional mechanical properties and bio-stability, is considered a promising alternative to traditional metal-based...
Polyetheretherketone (PEEK), renowned for its exceptional mechanical properties and bio-stability, is considered a promising alternative to traditional metal-based implants. However, the inferior bactericidal activity and the limited angiogenic and osteogenic properties of PEEK remain the three major obstacles to osseointegration . To overcome these obstacles, in this work, a versatile heterostructured nanocoating was conceived and equipped on PEEK. This nanocoating was designed to endow PEEK with the ability of photo-activated pathogen disinfection, along with enhanced angiogenesis and osteogenesis, effectively addressing the triple-barrier challenge towards osseointegration. The crafted nanocoating, encompassing diverse nutritional metal elements (Fe, Mg, and Sr) and a fusion peptide adept at promoting angiogenesis and osteogenesis, was seamlessly decorated onto PEEK. The engineered implant exhibited an antibacterial activity of over 94% upon near-infrared illumination by virtue of the photothermal conversion of the polyphenol nanocoating. Simultaneously, the decorated hierarchical nanocoatings synergistically promoted cellular adhesion and proliferation and up-regulated angiogenesis-/osteogenesis-associated cytokine expression in endothelial/osteoblast cells, resulting in superior angiogenic differentiation and osteoinductive capability . Moreover, an assay in a rabbit femoral defect model revealed that the decorated implant can achieve ameliorative osseointegrative fixation. Collectively, this work offers a practical and instructive clinical strategy to address the triple-barrier challenge associated with PEEK-based implants.
PubMed: 38913123
DOI: 10.1039/d4nr01453g -
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 -
Journal of Maxillofacial and Oral... Jun 2024The reconstitution of form and function after maxillofacial tumor resection or traumatic bony defects is a challenge when considering reconstructive options. The...
INTRODUCTION
The reconstitution of form and function after maxillofacial tumor resection or traumatic bony defects is a challenge when considering reconstructive options. The reconstructive options will depend upon whether the tissues to be replaced included bone alone or both bone and soft tissue (composite resection).
METHODOLOGY
This study was carried out on nine patients who with benign tumors or cysts of the mandible that required segmental resection. Mandibular reconstruction using mandibular transport distraction osteogenesis was performed for all the cases. Depending on whether the condyle was spared or sacrificed, the type of mandibular transport distractor either fixed on the remnant condyle-ramus unit or had a condylar component replacing the resected condyles. Depending on the location of the defect, transport distraction was carried our anterior to posterior or posterior to anterior.
RESULTS
A total of nine cases of benign mandibular pathologies were operated. Segmental resection with condylar preservation was carried out in seven cases, segmental resection with condylar resection was carried out in two cases. In cases with condylar resection, the reconstruction plate of the distractor device had a condylar component. Anterior to posterior transport distraction was carried out in seven cases, and posterior to anterior transport distraction carried out in two cases. The amount of distracted bone ranged from 38 to 46 mm.
CONCLUSION
Mandibular transport distraction osteogenesis offers a modality of reconstruction where the patient's native host bone is osteotomized and gradually distracted to induce the formation of regenerated osseous structure and soft tissue. Being cost-effective, not requiring a steep learning curve/long operative time, and not technically demanding as vascularized bone grafts/flaps, it is feasible in the Indian setup as a practical reconstructive option for benign jaw tumors.
PubMed: 38911433
DOI: 10.1007/s12663-023-01923-6 -
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