BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone m...The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant i...Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.展开更多
Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective a...Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.展开更多
Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the orig...The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.展开更多
BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bo...BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.展开更多
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.展开更多
Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological b...Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.展开更多
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relativ...Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation.While current anti-osteoporosis drugs,such as bisphosphonates and denosumab,predominantly focus on reducing bone resorption,osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk.Traditional Chinese medicines(TCMs)and their active ingredients have long been used in China for osteoporosis prevention and treatment.This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation.These compounds promote bone formation by regulating key transcription factors(RUNX2 and Osterix)and signaling pathways,including WNT/β-catenin,bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),oxidative stress,autophagy,and epigenetic regulation.Notably,certain natural products[e.g.,icariin(ICA)]exert their effects through multiple targets and pathways.Many of these natural products have demonstrated significant therapeutic efficacy in animal models,such as ovariectomized(OVX)mice.Our findings suggest that natural products with kidney-tonifying,anti-inflammatory,and antioxidant properties,as well as those inhibiting adipocyte differentiation,may hold promise for osteoporosis treatment.Additionally,we highlight current research gaps and propose future directions,including high-throughput screening and validation in diverse animal models,development of novel bone-targeting delivery systems,and identification of natural compounds targeting osteocytes.展开更多
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.展开更多
The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized...The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.展开更多
The specific surface area(S S)and pore size(D)exhibit an inherent trade-off in the microscale design of bone implants:larger pores typically correlate with reduced surface area and vice versa.This relationship has att...The specific surface area(S S)and pore size(D)exhibit an inherent trade-off in the microscale design of bone implants:larger pores typically correlate with reduced surface area and vice versa.This relationship has attracted notable attention because of its critical role in the regulation of cell adhesion and osteogenesis.However,it remains largely unclear how S S and D affect the generated bone tissue and dynamically change during long-term osteogenesis.Herein,by applying rigorous geometric mapping to minimal surfaces,we constructed precisely partitioned and layer-by-layer thickened tissue models to simulate osteogenesis across different temporal scales and thereby track the dynamic evolution of geometric characteristics,permeability,and mechanobiological tissue differentiation.The high-S S samples were found to facilitate the rapid formation of new bone tissue in the early stages.However,their smaller pores tended to cause occlusions,hindering further tissue development.In contrast,low-S S samples showed slower bone regeneration,but their larger pores provided adequate physical space for tissue regeneration and mass transport,ultimately promoting bone formation in the long term.Mechanobiological regulation suggests that fibrous tissue formation inhibits additional bone formation,establishing a dynamic equilibrium between osteogenesis and pore space to sustain nutrient/waste exchange throughout the regenerative process.Overall,smaller pores are preferable in implants for minimally loaded osteoplasty procedures focused on early-stage bone consolidation,whereas larger pores are preferable in dynamically loaded implants requiring prolonged mechanical stability.展开更多
Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with ...Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.展开更多
Recurrence of solid tumors after surgical resection is a major barrier to tissue regeneration.As an emerging treatment strategy,photo-thermo-electric therapy ablates tumor cells via photothermal effects and generates ...Recurrence of solid tumors after surgical resection is a major barrier to tissue regeneration.As an emerging treatment strategy,photo-thermo-electric therapy ablates tumor cells via photothermal effects and generates reactive oxygen species(ROS)via thermoelectric effects to disrupt heat shock proteins,thereby suppressing their protective function in tumor cells.However,conventional materials suffer from low thermoelectric efficiency and weak tissue penetration ability.In this study,we fabricated iodine-doped bismuth sulfide(I-Bi_(2)S_(3))nanorods with bonding heterostructures to improve thermoelectric performance.The approach employed iodine doping to introduce additional electrons,thereby regulating the band structure of Bi_(2)S_(3)and exploiting the dual low-energy vibration effect of the heterostructures to reduce thermal conductivity.More importantly,controlling the type of heterostructure modulated the bandgap width,thereby expanding the light absorption range to the higher-penetration near-infrared(NIR)-Ⅱregion for deep tissue treatment.The I-Bi_(2)S_(3)nanorods were incorporated into poly-L-lactic acid(PLLA)scaffolds to confer antitumor functionality.According to the results,the bonding heterostructures enhanced the conductivity of Bi_(2)S_(3)and reduced its thermal conductivity,significantly enhancing thermoelectric efficacy.The heterostructures reduced the bandgap of Bi_(2)S_(3)from 1.23 to 0.88 eV,enabling optical absorption in the NIR-Ⅱregion.The ROS tests showed that the PLLA/I-Bi_(2)S_(3)scaffold exhibited good photothermal effects and ROS generation under 1064-nm laser irradiation.The antitumor efficacy of the PLLA/I-Bi_(2)S_(3)scaffold reached 84.6%against MG-63 cells,demonstrating its exceptional potential in cancer treatment.展开更多
Background:Photodynamic therapy(PDT)may eradicate residual malignant cells following sarcoma resection,through reactive oxygen species(ROS)mediated cytotoxicity,thus improve clinical outcomes.This study aims to assess...Background:Photodynamic therapy(PDT)may eradicate residual malignant cells following sarcoma resection,through reactive oxygen species(ROS)mediated cytotoxicity,thus improve clinical outcomes.This study aims to assess the efficacy of 5-aminolevulinic acid(5-ALA)as a photosensitizer in combination with red light(RL)for PDT of bone sarcoma cells in vitro.Methods:Three bone sarcoma cell lines underwent treatment with 5-ALA and RL or sham-RL(SL).5-ALA uptake was assessed using flow cytometry.Production of ROS was measured using CellROX Green staining and fluorescence microscopy.Cell viability was assessed using Cell Counting Kit-8 assays.Results:All cell lines showed significant 5-ALA uptake in comparison to the 0 mM control(p<0.05).Production of ROS was significantly increased in cells treated with 5-ALA and RL,compared to those treated with RL and no 5-ALA or SL(p<0.05).Viability was significantly reduced in cells treated with 5-ALA and RL,compared to SL(p<0.05).At 72 h post-treatment,cell viability ranged from 6%-12%in 0.5 mM 5-ALA and RL-treated cells vs.90%-137%in 0.5 mM 5-ALA and SL-treated cells.Conclusion:5-ALA-based PDT led to the desired increased production of ROS and reduction in cell viability in all cell lines.These preliminary in vitro results warrant further study with multicellular spheroid or animal models and suggest PDT has potential to be used as an adjuvant therapy to surgical resection in sarcoma management.展开更多
The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is la...The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.展开更多
Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indic...Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.展开更多
As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially ...As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.展开更多
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金financially supported by the Guangzhou National Laboratory(grant#GZNL2025C02022,A.M.#QNPG2317,J.Z.)partially by the National Natural Science Foundation of China(31988101)。
文摘The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
文摘Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.
文摘Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
文摘The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.
文摘BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
基金supported by the National Natural Science Foundation of China(No.31800059)。
文摘Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation.While current anti-osteoporosis drugs,such as bisphosphonates and denosumab,predominantly focus on reducing bone resorption,osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk.Traditional Chinese medicines(TCMs)and their active ingredients have long been used in China for osteoporosis prevention and treatment.This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation.These compounds promote bone formation by regulating key transcription factors(RUNX2 and Osterix)and signaling pathways,including WNT/β-catenin,bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),oxidative stress,autophagy,and epigenetic regulation.Notably,certain natural products[e.g.,icariin(ICA)]exert their effects through multiple targets and pathways.Many of these natural products have demonstrated significant therapeutic efficacy in animal models,such as ovariectomized(OVX)mice.Our findings suggest that natural products with kidney-tonifying,anti-inflammatory,and antioxidant properties,as well as those inhibiting adipocyte differentiation,may hold promise for osteoporosis treatment.Additionally,we highlight current research gaps and propose future directions,including high-throughput screening and validation in diverse animal models,development of novel bone-targeting delivery systems,and identification of natural compounds targeting osteocytes.
基金supported by the National Natural Science Foundation of China (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
基金provided by the Joint Fund for Regional Innovation and Development(U23A20471)Beijing Natural Science Foundation(L242161,L241073,and 7232354)。
文摘The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.
基金financial support from the National Natural Science Foundation of China(No.52035012)the Guangdong Basic and Applied Basic Research Foundation(No.2025A1515012203)。
文摘The specific surface area(S S)and pore size(D)exhibit an inherent trade-off in the microscale design of bone implants:larger pores typically correlate with reduced surface area and vice versa.This relationship has attracted notable attention because of its critical role in the regulation of cell adhesion and osteogenesis.However,it remains largely unclear how S S and D affect the generated bone tissue and dynamically change during long-term osteogenesis.Herein,by applying rigorous geometric mapping to minimal surfaces,we constructed precisely partitioned and layer-by-layer thickened tissue models to simulate osteogenesis across different temporal scales and thereby track the dynamic evolution of geometric characteristics,permeability,and mechanobiological tissue differentiation.The high-S S samples were found to facilitate the rapid formation of new bone tissue in the early stages.However,their smaller pores tended to cause occlusions,hindering further tissue development.In contrast,low-S S samples showed slower bone regeneration,but their larger pores provided adequate physical space for tissue regeneration and mass transport,ultimately promoting bone formation in the long term.Mechanobiological regulation suggests that fibrous tissue formation inhibits additional bone formation,establishing a dynamic equilibrium between osteogenesis and pore space to sustain nutrient/waste exchange throughout the regenerative process.Overall,smaller pores are preferable in implants for minimally loaded osteoplasty procedures focused on early-stage bone consolidation,whereas larger pores are preferable in dynamically loaded implants requiring prolonged mechanical stability.
文摘Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.
基金National Key Research and Development Program of China(No.2023YFB4605800)The National Natural Science Foundation of China(Nos.52475362,52365046,and 52465041)+3 种基金Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)Jiangxi Provincial Key Laboratory of Additive Manufacturing of Implantable Medical Device(No.2024SSY11161)Jiangxi Provincial Department of Education Science and Technology Project(No.GJJ2400708)Jiangxi Province Science and Technology Program(Nos.20252BAC200317 and 20252BEJ730195)。
文摘Recurrence of solid tumors after surgical resection is a major barrier to tissue regeneration.As an emerging treatment strategy,photo-thermo-electric therapy ablates tumor cells via photothermal effects and generates reactive oxygen species(ROS)via thermoelectric effects to disrupt heat shock proteins,thereby suppressing their protective function in tumor cells.However,conventional materials suffer from low thermoelectric efficiency and weak tissue penetration ability.In this study,we fabricated iodine-doped bismuth sulfide(I-Bi_(2)S_(3))nanorods with bonding heterostructures to improve thermoelectric performance.The approach employed iodine doping to introduce additional electrons,thereby regulating the band structure of Bi_(2)S_(3)and exploiting the dual low-energy vibration effect of the heterostructures to reduce thermal conductivity.More importantly,controlling the type of heterostructure modulated the bandgap width,thereby expanding the light absorption range to the higher-penetration near-infrared(NIR)-Ⅱregion for deep tissue treatment.The I-Bi_(2)S_(3)nanorods were incorporated into poly-L-lactic acid(PLLA)scaffolds to confer antitumor functionality.According to the results,the bonding heterostructures enhanced the conductivity of Bi_(2)S_(3)and reduced its thermal conductivity,significantly enhancing thermoelectric efficacy.The heterostructures reduced the bandgap of Bi_(2)S_(3)from 1.23 to 0.88 eV,enabling optical absorption in the NIR-Ⅱregion.The ROS tests showed that the PLLA/I-Bi_(2)S_(3)scaffold exhibited good photothermal effects and ROS generation under 1064-nm laser irradiation.The antitumor efficacy of the PLLA/I-Bi_(2)S_(3)scaffold reached 84.6%against MG-63 cells,demonstrating its exceptional potential in cancer treatment.
文摘Background:Photodynamic therapy(PDT)may eradicate residual malignant cells following sarcoma resection,through reactive oxygen species(ROS)mediated cytotoxicity,thus improve clinical outcomes.This study aims to assess the efficacy of 5-aminolevulinic acid(5-ALA)as a photosensitizer in combination with red light(RL)for PDT of bone sarcoma cells in vitro.Methods:Three bone sarcoma cell lines underwent treatment with 5-ALA and RL or sham-RL(SL).5-ALA uptake was assessed using flow cytometry.Production of ROS was measured using CellROX Green staining and fluorescence microscopy.Cell viability was assessed using Cell Counting Kit-8 assays.Results:All cell lines showed significant 5-ALA uptake in comparison to the 0 mM control(p<0.05).Production of ROS was significantly increased in cells treated with 5-ALA and RL,compared to those treated with RL and no 5-ALA or SL(p<0.05).Viability was significantly reduced in cells treated with 5-ALA and RL,compared to SL(p<0.05).At 72 h post-treatment,cell viability ranged from 6%-12%in 0.5 mM 5-ALA and RL-treated cells vs.90%-137%in 0.5 mM 5-ALA and SL-treated cells.Conclusion:5-ALA-based PDT led to the desired increased production of ROS and reduction in cell viability in all cell lines.These preliminary in vitro results warrant further study with multicellular spheroid or animal models and suggest PDT has potential to be used as an adjuvant therapy to surgical resection in sarcoma management.
文摘The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.
基金financially supported by the Basic Science Center Program(T2288102)the Key Program of the National Natural Science Foundation of China(32230059)+3 种基金the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the Project supported by the Young Scientists Fund of the National Natural Science Foundation of China(32401128)Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251).
文摘Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.
基金supported by the National Natural Science Foundation of China(Nos.82160419 and 82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)。
文摘As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.
