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1.
Acta Biomater ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969080

RESUMO

The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. STATEMENT OF SIGNIFICANCE: Degradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups.

2.
Ann Med Surg (Lond) ; 86(6): 3786-3790, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38846825

RESUMO

Background: Denosumab is known to enhance callus formation while delaying remodeling. However, its effects on fracture healing are scarcely reported in the literature. This case report, to the best of our knowledge, is the first to report the potential effect of denosumab on a metatarsal fracture in an older adult patient, 4 months after administration, resulting in a favorable clinical course with early weight-bearing 17 days after the fracture. Presentation of case: A 73-year-old female sustained a right-foot second metatarsal fracture due to the fall of a heavy object. She has a history of diabetes mellitus, hypertension, and osteoporosis. Prior to sustaining the fracture, she received seven doses of denosumab spaced 6 months apart, with the last dose administered 4 months earlier. Furthermore, the patient was treated with a backsplint for 6 weeks. After 17 days, follow-up radiographs showed a large callus formation, with no pain and the ability to bear weight. Subsequent radiographs revealed a large callus with delayed remodeling. Discussion: This case report suggests that denosumab remains effective for promoting rapid callus formation even 4 months after administration for osteoporosis, despite delayed remodeling. This delay did not seem to have negative effects on the clinical outcomes, as the patient achieved weight-bearing within 17 days after sustaining the fracture. Conclusion: Denosumab may positively influence fracture healing in older adults with metatarsal fractures, potentially leading to delayed remodeling. However, further studies are needed to confirm these observations.

3.
Front Genet ; 15: 1408404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919952

RESUMO

Fracture healing is a complex process that involves multiple molecular events, and the regulation mechanism is not fully understood. We acquired miRNA and mRNA transcriptomes of mouse fractures from the Gene Expression Omnibus database (GSE76197 and GSE192542) and integrated the miRNAs and genes that were differentially expressed in the control and fracture groups to construct regulatory networks. There were 130 differentially expressed miRNAs and 4,819 differentially expressed genes, including 72 upregulated and 58 downregulated miRNAs, along with 2,855 upregulated and 1964 downregulated genes during early fracture healing. Gene ontology analysis revealed that most of the differentially expressed genes were enriched in the extracellular matrix (ECM) structure and the ECM organization. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested cell cycle, DNA replication, and mismatch repair were involved in the progression of fracture healing. Furthermore, we constructed a molecular network of miRNAs and mRNAs with inverse expression patterns to elucidate the molecular basis of miRNA-mRNA regulation in fractures. The regulatory network highlighted the potential targets, which may help to provide a mechanistic basis for therapies to improve fracture patient outcomes.

4.
Bioact Mater ; 39: 273-286, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38832305

RESUMO

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing. In this study, we aimed to develop an osteoanabolic therapy which activates the Wnt/ß-catenin pathway, a molecular driver of endochondral ossification. We hypothesize that using an mRNA-based therapeutic encoding ß-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes. To optimize a delivery platform built on recent advancements in liposomal technologies, two FDA-approved ionizable phospholipids, DLin-MC3-DMA (MC3) and SM-102, were used to fabricate unique ionizable lipid nanoparticle (LNP) formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model. Using firefly luciferase mRNA as a reporter gene to track and quantify transfection, SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection, minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs. The generated ß-cateninGOF mRNA encapsulated in SM-102 LNPs (SM-102-ß-cateninGOF mRNA) showed bioactivity in vitro through upregulation of downstream canonical Wnt genes, axin2 and runx2. When testing SM-102-ß-cateninGOF mRNA therapeutic in a murine tibia fracture model, histomorphometric analysis showed increased bone and decreased cartilage composition with the 45 µg concentration at 2 weeks post-fracture. µCT testing confirmed that SM-102-ß-cateninGOF mRNA promoted bone formation in vivo, revealing significantly more bone volume over total volume in the 45 µg group. Thus, we generated a novel mRNA-based therapeutic encoding a ß-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.

5.
Front Pharmacol ; 15: 1363421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915474

RESUMO

Background: Osteoking (OK) is prescribed in traditional Chinese medicine to accelerate fracture healing. Although some studies suggest the potential efficacy of OK for fracture healing, the evidence remains inconclusive. Aim: To systematically evaluate the safety of OK and its effect on fracture healing. Methods: Relevant authoritative databases were searched until 25 August 2023. Randomized controlled trials (RCTs) of patients with fractures treated with Osteoking were included. We evaluated the risk of bias using the Cochrane tool and performed a meta-analysis using the Review Manager 5.4 software package. Results: 13 studies involving 1123 participants were included. This meta-analysis showed that compared with observations in the control group, the OK group showed a shortened fracture healing time, increased fracture healing rate, reduced swelling regression time and ecchymosis regression time, and improved bone metabolism. In addition, the included studies did not report any serious side effects associated with the use of OK, and the mild side effects resolved without treatment. Conclusion: OK therapy is beneficial and safe for accelerating fracture healing, reducing swelling, eliminating ecchymosis, and improving bone metabolism. However, the meta-analysis results do not support OK treatment for improving the fracture healing rate at all fracture sites and reducing pain across all fracture sites. Further original, high-quality studies are needed to validate these findings.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=452430, identifier CRD42023452430.

6.
Aging Cell ; : e14212, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825965

RESUMO

Fracture healing complications increase with age, with higher rates of delayed unions and nonunions and an associated increase in morbidity and mortality in older adults. Macrophages have a dynamic role in fracture healing, and we have previously demonstrated that age-related changes in macrophages are associated with attenuated fracture repair in old mice. Here, we provide a single cell characterization of the immune cells involved in the early phase of fracture healing. We show that there were multiple transcriptionally distinct macrophage subpopulations present simultaneously within the healing tissue. Fracture healing was attenuated in old mice compared to young, and macrophages from the fracture callus of old mice demonstrated a pro-inflammatory phenotype compared to young. Interestingly, Trem2 expression was decreased in old macrophages compared to young. Young mice lacking Trem2 demonstrated attenuated fracture healing and inflammatory dysregulation similar to old mice. Trem2 dysregulation has previously been implicated in other age-related diseases, but its role in fracture healing is unknown. This work provides a robust characterization of the macrophage subpopulations involved in fracture healing, and further reveals the important role of Trem2 in fracture healing and may be a potential driver of age-related inflammatory dysregulation. Future work may further examine macrophages and Trem2 as potential therapeutic targets for management of fracture repair in older adults.

7.
J Orthop Surg Res ; 19(1): 370, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907263

RESUMO

BACKGROUND: Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study investigated the molecular mechanism and regulatory significance of lncRNA MAGI2-AS3 (MAGI2-AS3) in fracture healing. METHODS: Serum levels of MAGI2-AS3 in patients with normal and delayed fracture healing were verified by RT-qPCR assays. The predictive efficacy of MAGI2-AS3 for delayed fracture healing was analyzed by ROC curve. Osteogenic markers were quantified by RT-qPCR assays. MC3T3-E1 cell viability was detected using CCK-8 assay, and flow cytometry was utilized to measure cell apoptosis. The dual-luciferase reporter gene assay was used to determine the targeted binding between MAGI2-AS3 and miR-223-3p. RESULTS: Serum MAGI2-AS3 expression was decreased in patients with delayed fracture healing compared with patients with normal healing. Elevated MAGI2-AS3 resulted in an upregulation of the proliferative capacity of MC3T3-E1 cells and a decrease in mortality, along with increased levels of both osteogenic markers. However, after transfection silencing MAGI2-AS3, the trend was reversed. Additionally, miR-223-3p was the downstream target of MAGI2-AS3 and was controlled by MAGI2-AS3. miR-223-3p mimic reversed the promoting effects of MAGI2-AS3 overexpression on osteogenic marker levels and cell growth, and induced cell apoptosis. CONCLUSION: The upregulation of MAGI2-AS3 may expedite the healing of fracture patients by targeting miR-223-3p, offering a novel biomarker for diagnosing patients with delayed healing.


Assuntos
Regulação para Baixo , Consolidação da Fratura , MicroRNAs , RNA Longo não Codificante , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Consolidação da Fratura/genética , Consolidação da Fratura/fisiologia , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética
8.
Acta Ortop Bras ; 32(2): e278581, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933358

RESUMO

Objective: Identify the predictors associated with delayed union at 6 months and non-union at 12 months in tibial shaft fractures treated with intramedullary nailing (IMN). Methods: This retrospective longitudinal study included a cohort of 218 patients who sustained tibial shaft fractures and received IMN between January 2015 and March 2022. We gathered data on a range of risk factors, including patient demographics, trauma intensity, associated injuries, fracture characteristics, soft tissue injuries, comorbidities, addictions, and treatment-specific factors. We employed logistic bivariate regression analysis to explore the factors predictive of delayed union and non-union. Results: At the 6-month follow-up, the incidence of delayed union was 28.9%. Predictors for delayed union included flap coverage, high-energy trauma, open fractures, the use of external fixation as a staged treatment, the percentage of cortical contact in simple type fractures, RUST score, and postoperative infection. After 12 months, the non-union rate was 15.6%. Conclusion: the main predictors for non-union after IMN of tibial shaft fractures are related to the trauma energy. Furthermore, the initial treatment involving external fixation and postoperative infection also correlated with non-union. Level of Evidence III; Retrospective Longitudinal Study.


Objetivo: identificar os fatores preditivos associados ao atraso de consolidação em 6 meses e à não união em 12 meses em fraturas da diáfise da tíbia tratadas com haste intramedular (HIM). Métodos: O estudo longitudinal retrospectivo de coorte incluiu 218 pacientes, que apresentaram fraturas da díafise da tíbia e receberam HIM entre janeiro de 2015 e março de 2022. Os desfechos principais pesquisados foram atraso de consolidação em 6 meses de acompanhamento, e não união em 12 meses. Coletou-se dados de uma variedade de fatores de risco. Utilizou-se análise de regressão logística bivariada para explorar os fatores preditivos de atraso de consolidação e não união. Resultados: Aos 6 meses, a incidência de atraso de consolidação foi de 28,9%. Os preditores de atraso de consolidação incluem cobertura de retalho, trauma de alta energia, fraturas expostas, uso de fixação externa como tratamento estagiado, porcentagem de contato cortical em fraturas simples, escore RUST e infecção pós-operatória. Após 12 meses, a taxa de não união foi de 15,6%, com fatores preditivos sendo necessidade de cobertura por retalho, lesão vascular, trauma de alta energia, fraturas expostas, uso de fixação externa como tratamento estagiado, porcentagem de contato cortical em fraturas simples e infecção pós-operatória. Nível de Evidência III; Estudo Longitudinal Retrospectivo.

9.
Cells ; 13(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38920674

RESUMO

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing.


Assuntos
Regeneração Óssea , Consolidação da Fratura , Humanos , Regeneração Óssea/fisiologia , Animais , Células-Tronco/citologia , Transplante de Células-Tronco/métodos
10.
Artigo em Inglês | MEDLINE | ID: mdl-38839533

RESUMO

The sagittal split ramus osteotomy (SSRO) carries potential risks and complications. A double-blind, split-mouth, randomized clinical trial was performed, involving 30 patients undergoing mandibular setback. Advanced platelet-rich fibrin (A-PRF) was applied to one side, and the other side served as a control. The volume of postoperative drainage over 24 h was recorded. At 1, 2, and 5 days, and 3 months postsurgery, nerve recovery was assessed using the two-point discrimination test (TPD), while pain was evaluated using a visual analogue scale (VAS pain). Facial swelling was evaluated by taking linear measurements from facial reference points at the same time intervals. In the treatment group, the 24-hour drainage volume was lower (P = 0.011), pain was better on day 5 (P = 0.011), and TPD was better on day 2 (P = 0.011), day 5 (P = 0.007), and 3 months postoperatively (P = 0.020) than in the control group. There was also less facial swelling in the treatment group when compared to the baseline of 3 months postoperative (day 1, P = 0.012; day 2, P = 0.001; day 5, P = 0.011). The difference in bone mineral density (HU) at 3 months between the treatment group (469.7 ± 134.2) and the control group (348.3 ± 127.2) was statistically significant (P = 0.011), in favour of the treatment group. A-PRF may reduce postoperative complications such as neurosensory disturbance of the inferior alveolar nerve, pain, swelling, and drainage while enhancing bone healing in the osteotomy gap following SSRO. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Register (ChiCTR2200064534).

11.
Chirurgie (Heidelb) ; 2024 Jun 03.
Artigo em Alemão | MEDLINE | ID: mdl-38829545

RESUMO

The diagnosis and treatment of non-unions still represents an interdisciplinary challenge. Therefore, prevention, early detection and specific treatment are of great importance. Non-unions of the upper extremities, although less common than that of the lower extremities, requires special attention for successful treatment due to the central role of the shoulder girdle and arm in day to day activities. Successful treatment of non-unions requires a comprehensive evaluation of the patient's medical history, a thorough clinical examination and in particular radiological imaging. In order to effectively treat the pseudarthrosis it is crucial to distinguish between pseudarthroses that are suspected to be due to infections and those that are not. This article presents a treatment algorithm for managing both pseudarthrosis due to infection and pseudarthrosis without infection in the upper extremities.

12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38832464

RESUMO

OBJECTIVES: To investigate the effect of sinusoidal alternating electromagnetic field (SEMF) on fracture healing and its mechanism. METHODS: Femoral fracture model was established using SPF male Wistar rats, 30 model rats were randomly divided into model control (MC) and SEMF groups with 15 rats in each group. The SEMF group was given 50 Hz 1.8 mT for 90 min every day, and the MC group was not treated. X-ray examinations were performed every two weeks to determine the formation of bone scabs in each group of rats. Three rats were sacrificed after 2 and 4 weeks of treatment in both groups. Protein was extracted from the fractured femurs, and the expression of type Ⅰ collagen (COL-1), Osterix (OSX), Runt-related transcription factor 2 (RUNX2), and vascular endothelial growth factor (VEGF) protein level was detected by immunoblotting. After 8 weeks, the femur on the operated side was taken for micro-CT scanning to observe fracture healing, angiography to observe blood vessel growth, and organs such as hearts, livers, spleens, lungs, and kidneys were taken for safety evaluation by hematoxylin-eosin staining (HE staining). RESULTS: The bone scab scores of the SEMF group were significantly higher than those of the MC group after 2, 4, 6, and 8 weeks of treatment (all P<0.01); the fracture healing of the SEMF group was better than that of the MC group after 8 weeks, and the bone volume scores of the two groups were 0.243±0.012 and 0.186±0.008, respectively, with statistically significant differences (P<0.01); and the number of blood vessels in the SEMF group was also more than that of the MC group after 8 weeks. The results of protein blotting method showed that the protein expression of VEGF, COL-1, RUNX2, and OSX was higher in the SEMF group than in the MC group after 2 and 4 weeks of treatment (all P<0.05), and the HE staining showed that there was no abnormality in histopathological observation of examined organs in both groups. CONCLUSIONS: SEMF can accelerate fracture healing by promoting the expression of osteogenic factors and vascular proliferation without significant adverse effects.

13.
J Orthop Surg Res ; 19(1): 343, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849896

RESUMO

BACKGROUND: Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. METHODS: 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. RESULTS: Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. CONCLUSIONS: LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.


Assuntos
Biomarcadores , Diferenciação Celular , Consolidação da Fratura , Osteoblastos , RNA Longo não Codificante , RNA Longo não Codificante/genética , Humanos , Feminino , Biomarcadores/sangue , Biomarcadores/metabolismo , Consolidação da Fratura/genética , Consolidação da Fratura/fisiologia , Idoso , Diferenciação Celular/genética , Osteoblastos/metabolismo , Animais , Camundongos , MicroRNAs/genética , Osteoporose/genética , Osteoporose/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/genética , Proliferação de Células/genética , Regulação para Cima
14.
J Orthop Traumatol ; 25(1): 28, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789881

RESUMO

Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Transplante de Células-Tronco Mesenquimais , Humanos , Regeneração Óssea/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Consolidação da Fratura/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Osteogênese/fisiologia
15.
Orthop Clin North Am ; 55(3): 383-392, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782509

RESUMO

Although the impact that vitamin D has on bone healing is uncertain in foot and ankle (F&A) surgery, there is support for vitamin D supplementation (2000 IU/day) with calcium (1 g/day) to promote bone healing. Although orthopedic F&A surgeons are frequently the first provider to detect the harbingers of osteoporosis by the occurrence of fragility fractures, this should trigger referral to the appropriate specialist for assessment and treatment. There is circumstantial evidence suggesting a role of hypovitaminosis D in bone marrow edema syndrome and possibly osteochondritis dissecans. There should be a low threshold for assessing vitamin D levels in such patients.


Assuntos
Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/uso terapêutico , Vitamina D/sangue , Vitamina D/administração & dosagem , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Suplementos Nutricionais , Procedimentos Ortopédicos/efeitos adversos , Pé/cirurgia , Tornozelo/cirurgia
16.
J Clin Med ; 13(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38792446

RESUMO

The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked plating technology enabled new strategies for the controlled dynamization of fractures, such as far cortical locking (FCL) screws or active plates with elastically suspended screw holes. However, these strategies did not allow for the use of non-locking screws, which are typically used to reduce bone fragments to the plate. This study documents the first in vivo study on the healing of ovine tibia osteotomies stabilized with an advanced active plate (AAP). This AAP allowed plate application using any combination of locking and non-locking screws to support a wide range of plate application techniques. At week 9 post-surgery, tibiae were harvested and tested in torsion to failure to assess the healing strength. The five tibiae stabilized with an AAP regained 54% of their native strength and failed by spiral fracture through a screw hole, which did not involve the healed osteotomy. In comparison, tibiae stabilized with a standard locking plate recovered 17% of their strength and sustained failure through the osteotomy. These results further support the stimulatory effect of controlled motion on fracture healing. As such, the controlled dynamization of locked plating constructs may hold the potential to reduce healing complications and may shorten the time to return to function. Integrating controlled dynamization into fracture plates that support a standard fixation technique may facilitate the clinical adoption of dynamic plating.

17.
Bioact Mater ; 38: 422-437, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38770427

RESUMO

Delayed bone-healing of senile osteoporotic fractures remains a clinical challenge due to the alterations caused by aging in bone and immune systems. The novel biomaterials that address the deficiencies in both skeletal cells and immune systems are required to effectively treat the bone injuries of older patients. Zinc (Zn) has shown promise as a biodegradable material for use in orthopedic implants. To address the bone-healing deficiencies in elderly patients with bone injuries, we developed a biodegradable Zn-based alloy (Zn-2Cu-0.5Zr) with enhanced mechanical properties, including a yield strength of 198.7 MPa and ultimate tensile strength of 217.6 MPa, surpassing those of pure Zn and Zn-2Cu alloys. Cytotoxicity tests conducted on bone marrow mesenchymal stem cells (BMSCs) and MC3T3-E1 cells demonstrated that the extracts from Zn-2Cu-0.5Zr alloy exhibited no observable cytotoxic effects. Furthermore, the extracts of Zn-2Cu-0.5Zr alloy exhibited significant anti-inflammatory effects through regulation of inflammation-related cytokine production and modulation of macrophage polarization. The improved immune-osteo microenvironment subsequently contributed to osteogenic differentiation of BMSCs. The potential therapeutic application of Zn-2Cu-0.5Zr in senile osteoporotic fracture was tested using a rat model of age-related osteoporosis. The Zn-2Cu-0.5Zr alloy met the requirements for load-bearing applications and accelerated the healing process in a tibial fracture in aged rats. The imaging and histological analyses showed that it could accelerate the bone-repair process and promote the fracture healing in senile osteoporotic rats. These findings suggest that the novel Zn-2Cu-0.5Zr alloy holds potential for influencing the immunomodulatory function of macrophages and facilitating bone repair in elderly individuals with osteoporosis.

18.
Front Surg ; 11: 1376441, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756355

RESUMO

Delayed union and non-union of fractures continue to be a major problem in trauma and orthopedic surgery. These cases are challenging for the surgeon. In addition, these patients suffer from multiple surgeries, pain and disability. Furthermore, these cases are a major burden on healthcare systems. The scientific community widely agrees that the stability of fixation plays a crucial role in determining the outcome of osteosynthesis. The extent of stabilization affects factors like fracture gap strain and fluid flow, which, in turn, influence the regenerative processes positively or negatively. Nonetheless, a growing body of literature suggests that during the fracture healing process, there exists a critical time frame where intervention can stimulate the bone's return to its original form and function. This article provides a summary of existing evidence in the literature regarding the impact of different levels of fixation stability on the strain experienced by newly forming tissues. We will also discuss the timing and nature of this "window of opportunity" and explore how current knowledge is driving the development of new technologies with design enhancements rooted in mechanobiological principles.

19.
Med J Islam Repub Iran ; 38: 25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783980

RESUMO

Background: In extra-articular distal femoral fractures (EDFFs), nonunion is a serious complication that occurs rarely. In this study, we examined how longer preservation of initial fracture hematoma by delaying the osteosynthesis (OS) affects the fracture union. Methods: In a retrospective cohort study, 98 EDFF patients were included. The OS was done within 2 days of injury in 50 patients (early OS group) and after 2 days of injury in 48 patients (late OS group). Time to callus formation and fracture union, bleeding amount, surgical duration, pain, knee range of motion, knee function, and postoperative complications, including the nonunion, knee deformity, infection, and revision, were compared between the 2 groups. Statistical analyses were done with SPSS. A comparison of the mean between the 2 groups was made with an independent t test or its nonparametric counterpart. A comparison of categorical variables between the 2 groups was made using a chi-square or the Fisher's exact test. P ˂ 0.05 was considered statistically significant. Results: The mean time to callus formation was 47.1 ± 17.3 days in the early OS group and 46.9 ± 19.7 in the late OS group (P = 0.950). The mean time to fracture union was 114.9 ± 21 in the early OS group and 117.4 ± 28.8 days in the late OS group (P = 0.630). The mean operation time and bleeding amount between the 2 groups did not differ significantly (P = 0.230 and P = 0.340, respectively). The knee range of motion, pain, and function were not notably different (P = 0.620, P = 0.790, and P = 0.770, respectively). Nonunion occurred in 3 patients of early OS and 2 patients of the late OS group. Other complications were also comparable in the 2 study groups. Conclusion: Delayed OA in EDFF patients has no significant effect on bone healing and fracture union. Future standard studies are required to confirm these results.

20.
BMC Musculoskelet Disord ; 25(1): 353, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724941

RESUMO

BACKGROUND: External fixation is widely used in the treatment of traumatic fractures; however, orthopedic surgeons encounter challenges in deciding the optimal time for fixator removal. The axial load-share ratio (LS) of the fixator is a quantitative index to evaluate the stiffness of callus healing. This paper introduces an innovative method for measuring the LS and assesses the method's feasibility and efficacy. Based on a novel hexapod LS-measurement system, the proposed method is to improve the convenience and precision of measuring LS in vivo, hence facilitating the safe removal of external fixators. METHODS: A novel hexapod system is introduced, including its composition, theoretical model, and method for LS measurement. We conducted a retrospective study on 82 patients with tibial fractures treated by the Taylor Spatial Frame in our hospital from September 2018 to June 2020, of which 35 took LS measurements with our novel method (Group I), and 47 were with the traditional method (Group II). The external fixator was removed when the measurement outcome (LS < 10%) was consistent with the surgeon's diagnosis based on the clinical and radiological assessment (bone union achieved). RESULTS: No significant difference was found in the fracture healing time (mean 25.3 weeks vs. 24.9 weeks, P > 0.05), frame-wearing duration (mean 25.5 weeks vs. 25.8 weeks, P > 0.05), or LS measurement frequency (mean 1.1 times vs. 1.2 times, P > 0.05). The measurement system installation time in Group I was significantly shorter compared to Group II (mean 14.8 min vs. 81.3 min, P < 0.001). The LS value of the first measurement in Group I was lower than that of Group II (mean 5.1% vs. 6.9%, P = 0.011). In Group I, the refracture rate was 0, but in Group II it was 4.3% (2/47, P > 0.05). CONCLUSION: The novel hexapod LS-measurement system and involved method demonstrated enhanced convenience and precision in measuring the LS of the external fixator in vivo. The LS measurement indicates the callus stiffness of fracture healing, and is applicable to evaluate the safety of removing the fixator. Consequently, it is highly recommended for widespread adoption in clinical practice.


Assuntos
Remoção de Dispositivo , Fixadores Externos , Fixação de Fratura , Consolidação da Fratura , Fraturas da Tíbia , Humanos , Feminino , Fraturas da Tíbia/cirurgia , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Fixação de Fratura/instrumentação , Fixação de Fratura/métodos , Remoção de Dispositivo/métodos , Suporte de Carga , Adulto Jovem , Idoso , Estudos de Viabilidade , Desenho de Equipamento
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