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
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
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
目的探讨双能量CT Bone Marrow Edema(骨髓水肿)定量评估肋骨骨折演变时间节点的价值。方法收集60例双能量CT扫描的胸部外伤患者,利用CT Bone Marrow Edema技术,标准化定量肋骨骨折处骨髓水肿区域及骨折两侧1 cm处正常区域骨髓CT值,得...目的探讨双能量CT Bone Marrow Edema(骨髓水肿)定量评估肋骨骨折演变时间节点的价值。方法收集60例双能量CT扫描的胸部外伤患者,利用CT Bone Marrow Edema技术,标准化定量肋骨骨折处骨髓水肿区域及骨折两侧1 cm处正常区域骨髓CT值,得到三期骨髓水肿标准化CT值增量与VNCa标准化CT值增量。对数值变量行统计学描述,并对三期骨髓水肿标准化CT值增量、VNCa标准化CT值增量进行各自组间比较及两两间比较,对有差异的组别行诊断效能比较,由接受者工作特征(ROC)曲线下面积(AUC)进行评估,并计算Cut-off值。结果三期骨髓水肿标准化CT值增量及VNCa标准化CT值增量组间均有统计学意义(H=10.788,p=0.005;F=115.787,p=0.000),其中,软骨痂期(纤维性骨痂期)与硬骨痂-重塑期骨髓水肿标准化CT值增量有统计学意义(H=54.958,p=0.003),其余两两间无统计学意义(分别为H=-25.603,p=0.183;H=29.354,p=0.113)。而三期VNCa标准化CT值增量两两间均有统计学意义(P均为0.000)。ROC曲线鉴别软骨痂期(纤维性骨痂期)与硬骨痂-重塑期骨髓水肿标准化CT值增量曲线下面积为0.652,Cut-off值为81.575 Hu,鉴别血肿炎症机化期与软骨痂期(纤维性骨痂期)VNCa标准化CT值增量曲线下面积为0.668,Cut-off值为55.700 Hu,鉴别软骨痂期(纤维性骨痂期)与硬骨痂-重塑期VNCa标准化CT值增量曲线下面积为0.905,Cut-off值为37.625 Hu。结论通过双能量CT Bone Marrow Edema可定量评估肋骨骨折演变时间节点,骨折时间演变的标准化CT值增量差异性可为法医鉴定骨折处于不同时间段提供理论依据。通过标准化CT值增量Cut-off值可一定程度上预测骨折所处时间阶段,为法医在鉴定肋骨骨折方面提供定量依据。展开更多
Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr...Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.展开更多
Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,ha...Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in OA.While the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal humerus.This paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA treatment.The iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced morbidity.The integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic efficacy.However,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical outcomes.Future directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting strategies.Ultimately,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaff...Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings.Thus,we aimed to enhance the bone repair ability of polycaprolactone(PCL)scaffolds by incorporating osteoinductive amorphous calcium phosphate(ACP)with immune-regulating zinc ions(ACP(Zn),ACZP),to create a favorable immunomodulatory microenvironment.After one day of co-culture with PCL-ACZP,the spreading area of macrophage cells was significantly higher than that from the original PCL scaffold.Additionally,over 32.1%of macrophages exhibited M2 polarization within three days of co-culture.The PCLACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells.After eight weeks of implantation in a rat femoral condyle defect,the BV/TV from the PCL-ACZP group reached 32.9%,1.4 times of that from the PCL group.Furthermore,the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits,resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings.This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.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
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal t...Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.展开更多
Age-related osteoporosis poses a significant challenge in musculoskeletal health;a condition characterized by reduced bone density and increased fracture susceptibility in older individuals necessitates a better under...Age-related osteoporosis poses a significant challenge in musculoskeletal health;a condition characterized by reduced bone density and increased fracture susceptibility in older individuals necessitates a better understanding of underlying molecular and cellular mechanisms.Emerging evidence suggests that osteocytes are the pivotal orchestrators of bone remodeling and represent novel therapeutic targets for age-related bone loss.Our study uses the prematurely aged PolgD257A/D257A(PolgA)mouse model to scrutinize age-and sex-related alterations in musculoskeletal health parameters(frailty,grip strength,gait data),bone and particularly the osteocyte lacuno-canalicular network(LCN).Moreover,a new quantitative in silico image analysis pipeline is used to evaluate the alterations in the osteocyte network with aging.Our findings underscore the pronounced degenerative changes in the musculoskeletal health parameters,bone,and osteocyte LCN in PolgA mice as early as 40 weeks,with more prominent alterations evident in aged males.Our findings suggest that the PolgA mouse model serves as a valuable model for studying the cellular mechanisms underlying age-related bone loss,given the comparable aging signs and age-related degeneration of the bone and the osteocyte network observed in naturally aging mice and elderly humans.展开更多
Bone tissue relies on the intricate interplay between blood vessels and nerve fibers,both are essential for many physiological and pathological processes of the skeletal system.Blood vessels provide the necessary oxyg...Bone tissue relies on the intricate interplay between blood vessels and nerve fibers,both are essential for many physiological and pathological processes of the skeletal system.Blood vessels provide the necessary oxygen and nutrients to nerve and bone tissues,and remove metabolic waste.Concomitantly,nerve fibers precede blood vessels during growth,promote vascularization,and influence bone cells by secreting neurotransmitters to stimulate osteogenesis.Despite the critical roles of both components,current biomaterials generally focus on enhancing intraosseous blood vessel repair,while often neglecting the contribution of nerves.Understanding the distribution and main functions of blood vessels and nerve fibers in bone is crucial for developing effective biomaterials for bone tissue engineering.This review first explores the anatomy of intraosseous blood vessels and nerve fibers,highlighting their vital roles in bone embryonic development,metabolism,and repair.It covers innovative bone regeneration strategies directed at accelerating the intrabony neurovascular system over the past 10 years.The issues covered included material properties(stiffness,surface topography,pore structures,conductivity,and piezoelectricity)and acellular biological factors[neurotrophins,peptides,ribonucleic acids(RNAs),inorganic ions,and exosomes].Major challenges encountered by neurovascularized materials during their clinical translation have also been highlighted.Furthermore,the review discusses future research directions and potential developments aimed at producing bone repair materials that more accurately mimic the natural healing processes of bone tissue.This review will serve as a valuable reference for researchers and clinicians in developing novel neurovascularized biomaterials and accelerating their translation into clinical practice.By bridging the gap between experimental research and practical application,these advancements have the potential to transform the treatment of bone defects and significantly improve the quality of life for patients with bone-related conditions.展开更多
Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.T...Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.This study proposes a sinusoidal-based lattice structure for an ultralow and widely tunable modulus design,aiming to match diverse bone tissue requirements and enhance biomechanical compatibility.Parametric modeling and finite element analysis were used to evaluate the performance of this structure.Results show that,within the design range suitable for bone growth,the elastic modulus of this lattice structure is tunable over a wide range,from 0.09 to 32.67 GPa,outperforming existing porous structures.The lowest value closely matched the minimum mechanical properties of human cancellous bone among porous structures.Moreover,the structure exhibited distinct anisotropic characteristics,allowing for directional design based on mechanical requirements.The structure’s permeability ranged from 1.19×10^(-8) m^(2) to 2.3×10^(-7) m^(2),making it highly compatible with human cancellous bone and meeting the requirements of orthopedic implants.Samples with porosities ranging from 46% to 87% were successfully fabricated using powder bed fusion additive manufacturing,validating the simulation predictions.This tunable low-modulus lattice structure provides a novel approach for developing personalized orthopedic implants,particularly for patients with specialized needs such as osteoporosis,and can potentially enhance biomechanical compatibility and long-term stability.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals i...The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated,the intimate relationship between the central nervous system and bone remains less understood,yet it has emerged as a hot topic in the bone field.In this review,we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism,either intact or after injury.First,we explored mechanistic studies linking specific brain nuclei with bone homeostasis,including the ventromedial hypothalamus,arcuate nucleus,paraventricular hypothalamic nucleus,amygdala,and locus coeruleus.We then focused on the characteristics of bone innervation and nerve subtypes,such as sensory,sympathetic,and parasympathetic nerves.Moreover,we summarized the molecular features and regulatory functions of these nerves.Finally,we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration.Therefore,considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process,ultimately benefiting future clinical translation.展开更多
OBJECTIVE:To explore the efficacy and safety of acupuncture combined with atlantoaxial joint bone-setting therapy for the treatment of Tourette syndrome.METHODS:We randomly divided 600 patients at a ratio of 1∶1∶1 i...OBJECTIVE:To explore the efficacy and safety of acupuncture combined with atlantoaxial joint bone-setting therapy for the treatment of Tourette syndrome.METHODS:We randomly divided 600 patients at a ratio of 1∶1∶1 into three groups:group A(acupuncture combined with atlantoaxial joint bone setting therapy group),group B(acupuncture group),and group C(tiapride group).After two months of treatment,the Yale global tic severity scale(YGTSS)score reduction,improvement in social function impairment,clinical efficacy,and long-term efficacy in the three groups were compared.RESULTS:After treatment,in the analysis of YGTSS score reduction,social function impairment improvement,the clinical control rate,and long-term efficacy,the results were all Group A>Group B>Group C,with a statistically significant difference(P<0.05).However,the total clinical efficacy of treatment in group A(94.9%)was not significantly different from that in group B(91.8%).Adverse reactions did not occur in groups A and B,and several adverse reactions occurred in 29%(n=58)of the group C patients.CONCLUSION:Compared with traditional drug therapy,acupuncture combined with atlantoaxial joint bone setting therapy has better clinical and long-term efficacy.This treatment strategy can improve the social function of children and prevent adverse reactions to drugs.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.
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.
文摘目的探讨双能量CT Bone Marrow Edema(骨髓水肿)定量评估肋骨骨折演变时间节点的价值。方法收集60例双能量CT扫描的胸部外伤患者,利用CT Bone Marrow Edema技术,标准化定量肋骨骨折处骨髓水肿区域及骨折两侧1 cm处正常区域骨髓CT值,得到三期骨髓水肿标准化CT值增量与VNCa标准化CT值增量。对数值变量行统计学描述,并对三期骨髓水肿标准化CT值增量、VNCa标准化CT值增量进行各自组间比较及两两间比较,对有差异的组别行诊断效能比较,由接受者工作特征(ROC)曲线下面积(AUC)进行评估,并计算Cut-off值。结果三期骨髓水肿标准化CT值增量及VNCa标准化CT值增量组间均有统计学意义(H=10.788,p=0.005;F=115.787,p=0.000),其中,软骨痂期(纤维性骨痂期)与硬骨痂-重塑期骨髓水肿标准化CT值增量有统计学意义(H=54.958,p=0.003),其余两两间无统计学意义(分别为H=-25.603,p=0.183;H=29.354,p=0.113)。而三期VNCa标准化CT值增量两两间均有统计学意义(P均为0.000)。ROC曲线鉴别软骨痂期(纤维性骨痂期)与硬骨痂-重塑期骨髓水肿标准化CT值增量曲线下面积为0.652,Cut-off值为81.575 Hu,鉴别血肿炎症机化期与软骨痂期(纤维性骨痂期)VNCa标准化CT值增量曲线下面积为0.668,Cut-off值为55.700 Hu,鉴别软骨痂期(纤维性骨痂期)与硬骨痂-重塑期VNCa标准化CT值增量曲线下面积为0.905,Cut-off值为37.625 Hu。结论通过双能量CT Bone Marrow Edema可定量评估肋骨骨折演变时间节点,骨折时间演变的标准化CT值增量差异性可为法医鉴定骨折处于不同时间段提供理论依据。通过标准化CT值增量Cut-off值可一定程度上预测骨折所处时间阶段,为法医在鉴定肋骨骨折方面提供定量依据。
基金supported by the Natural Science Fund of Fujian Province,No.2020J011058(to JK)the Project of Fujian Provincial Hospital for High-level Hospital Construction,No.2020HSJJ12(to JK)+1 种基金the Fujian Provincial Finance Department Special Fund,No.(2021)848(to FC)the Fujian Provincial Major Scientific and Technological Special Projects on Health,No.2022ZD01008(to FC).
文摘Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.
文摘Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in OA.While the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal humerus.This paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA treatment.The iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced morbidity.The integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic efficacy.However,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical outcomes.Future directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting strategies.Ultimately,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金financially supported by the National Natural Science Foundation of China(Nos.82203680 and 52273278)the Natural Scientific Foundation of Liaoning Province(No.2021-MS-176)+1 种基金Shenyang Bureau of Science and Technology(No.RC230527)the Central Guidance Funding for Local Scientific and Techno-logical Development in Liaoning(No.2023JH6/100100029).
文摘Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings.Thus,we aimed to enhance the bone repair ability of polycaprolactone(PCL)scaffolds by incorporating osteoinductive amorphous calcium phosphate(ACP)with immune-regulating zinc ions(ACP(Zn),ACZP),to create a favorable immunomodulatory microenvironment.After one day of co-culture with PCL-ACZP,the spreading area of macrophage cells was significantly higher than that from the original PCL scaffold.Additionally,over 32.1%of macrophages exhibited M2 polarization within three days of co-culture.The PCLACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells.After eight weeks of implantation in a rat femoral condyle defect,the BV/TV from the PCL-ACZP group reached 32.9%,1.4 times of that from the PCL group.Furthermore,the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits,resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings.This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.
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.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
基金supported by the National Natural Science Foundation of China(32171354,82222015,82171001)The National Key Research and Development Program of China2023YFC2413600Research Funding from West China School/Hospital of Stomatology,Sichuan University(No.RCDWIS2023-1).
文摘Infectious bone defects represent a substantial challenge in clinical practice,necessitating the deployment of advanced therapeutic strategies.This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism.The system is predicated on a hydrogel matrix that is thermally responsive,characteristic of bone defect sites,facilitating controlled and site-specific drug release.The cornerstone of this system is the incorporation of mild photothermal nanoparticles,which are activated within the temperature range of 40–43°C,thereby enhancing the precision and efficacy of drug delivery.Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents,mitigating systemic side effects and bolstering efficacy at the defect site.The synchronized pulsed release,cooperated with mild photothermal therapy,effectively addresses infection control,and promotes bone regeneration.This approach signifies a considerable advancement in the management of infectious bone defects,offering an effective and patient-centric alternative to traditional methods.Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios,underscoring its transformative potential in the realm of regenerative medicine.
基金the European Research Council(ERC Advanced MechAGE-ERC-2016-ADG-741883)the Swiss National Science Foundation(no.188522).
文摘Age-related osteoporosis poses a significant challenge in musculoskeletal health;a condition characterized by reduced bone density and increased fracture susceptibility in older individuals necessitates a better understanding of underlying molecular and cellular mechanisms.Emerging evidence suggests that osteocytes are the pivotal orchestrators of bone remodeling and represent novel therapeutic targets for age-related bone loss.Our study uses the prematurely aged PolgD257A/D257A(PolgA)mouse model to scrutinize age-and sex-related alterations in musculoskeletal health parameters(frailty,grip strength,gait data),bone and particularly the osteocyte lacuno-canalicular network(LCN).Moreover,a new quantitative in silico image analysis pipeline is used to evaluate the alterations in the osteocyte network with aging.Our findings underscore the pronounced degenerative changes in the musculoskeletal health parameters,bone,and osteocyte LCN in PolgA mice as early as 40 weeks,with more prominent alterations evident in aged males.Our findings suggest that the PolgA mouse model serves as a valuable model for studying the cellular mechanisms underlying age-related bone loss,given the comparable aging signs and age-related degeneration of the bone and the osteocyte network observed in naturally aging mice and elderly humans.
基金supported by the Foundation of National Clinical Research Center for Oral Diseases(LCA202204)the Key Research and Development Program of Shaanxi(2024GH-YBXM-19)+7 种基金the Clinical New Technology Program of Air Force Medical University(LX2023-306)the China Postdoctoral Science Foundation(2019M653969)the Thousand Talents Plan of Shaanxi Province(to Jing Wang)the National Natural Science Foundation of China(82101069,22205257)the Logistics Independent Research Project of PLA(to Yang Jiao)the Beijing Natural Science Foundation(7242279),the Beijing Nova Program(20230484283)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Open Project of State Key Laboratory of Trauma and Chemical poisoning(SKLO202401).
文摘Bone tissue relies on the intricate interplay between blood vessels and nerve fibers,both are essential for many physiological and pathological processes of the skeletal system.Blood vessels provide the necessary oxygen and nutrients to nerve and bone tissues,and remove metabolic waste.Concomitantly,nerve fibers precede blood vessels during growth,promote vascularization,and influence bone cells by secreting neurotransmitters to stimulate osteogenesis.Despite the critical roles of both components,current biomaterials generally focus on enhancing intraosseous blood vessel repair,while often neglecting the contribution of nerves.Understanding the distribution and main functions of blood vessels and nerve fibers in bone is crucial for developing effective biomaterials for bone tissue engineering.This review first explores the anatomy of intraosseous blood vessels and nerve fibers,highlighting their vital roles in bone embryonic development,metabolism,and repair.It covers innovative bone regeneration strategies directed at accelerating the intrabony neurovascular system over the past 10 years.The issues covered included material properties(stiffness,surface topography,pore structures,conductivity,and piezoelectricity)and acellular biological factors[neurotrophins,peptides,ribonucleic acids(RNAs),inorganic ions,and exosomes].Major challenges encountered by neurovascularized materials during their clinical translation have also been highlighted.Furthermore,the review discusses future research directions and potential developments aimed at producing bone repair materials that more accurately mimic the natural healing processes of bone tissue.This review will serve as a valuable reference for researchers and clinicians in developing novel neurovascularized biomaterials and accelerating their translation into clinical practice.By bridging the gap between experimental research and practical application,these advancements have the potential to transform the treatment of bone defects and significantly improve the quality of life for patients with bone-related conditions.
基金supported by National Key R&D Program of China(Grant No.2022YFB4600500)Fundamental Research Funds for the Central Universities,and the Program for Innovation Team of Shaanxi Province(Grant No.2023-CX-TD-17).
文摘Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.This study proposes a sinusoidal-based lattice structure for an ultralow and widely tunable modulus design,aiming to match diverse bone tissue requirements and enhance biomechanical compatibility.Parametric modeling and finite element analysis were used to evaluate the performance of this structure.Results show that,within the design range suitable for bone growth,the elastic modulus of this lattice structure is tunable over a wide range,from 0.09 to 32.67 GPa,outperforming existing porous structures.The lowest value closely matched the minimum mechanical properties of human cancellous bone among porous structures.Moreover,the structure exhibited distinct anisotropic characteristics,allowing for directional design based on mechanical requirements.The structure’s permeability ranged from 1.19×10^(-8) m^(2) to 2.3×10^(-7) m^(2),making it highly compatible with human cancellous bone and meeting the requirements of orthopedic implants.Samples with porosities ranging from 46% to 87% were successfully fabricated using powder bed fusion additive manufacturing,validating the simulation predictions.This tunable low-modulus lattice structure provides a novel approach for developing personalized orthopedic implants,particularly for patients with specialized needs such as osteoporosis,and can potentially enhance biomechanical compatibility and long-term stability.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
基金supported by the Health&Medical Research Fund(18190481)the General Research Fund(14120520).
文摘The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated,the intimate relationship between the central nervous system and bone remains less understood,yet it has emerged as a hot topic in the bone field.In this review,we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism,either intact or after injury.First,we explored mechanistic studies linking specific brain nuclei with bone homeostasis,including the ventromedial hypothalamus,arcuate nucleus,paraventricular hypothalamic nucleus,amygdala,and locus coeruleus.We then focused on the characteristics of bone innervation and nerve subtypes,such as sensory,sympathetic,and parasympathetic nerves.Moreover,we summarized the molecular features and regulatory functions of these nerves.Finally,we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration.Therefore,considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process,ultimately benefiting future clinical translation.
基金Supported by Traditional Chinese medicine foundation of Zhejiang province:Clinical Study on the Correlation Between Tourette Syndrome and Anatomical Changes in the Atlantoaxial Joint(2010ZB162)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission:Study on Protein Fingerprinting of Tourette Syndrome(2011KYB142)+1 种基金Renowned Traditional Chinese Medicine Expert Inheritance Studio Construction Project of Zhejiang province(No.GZS2020049)Key Disciplines of Traditional Chinese Medicine Foundation of Zhejiang Province(2012-XK-D20)。
文摘OBJECTIVE:To explore the efficacy and safety of acupuncture combined with atlantoaxial joint bone-setting therapy for the treatment of Tourette syndrome.METHODS:We randomly divided 600 patients at a ratio of 1∶1∶1 into three groups:group A(acupuncture combined with atlantoaxial joint bone setting therapy group),group B(acupuncture group),and group C(tiapride group).After two months of treatment,the Yale global tic severity scale(YGTSS)score reduction,improvement in social function impairment,clinical efficacy,and long-term efficacy in the three groups were compared.RESULTS:After treatment,in the analysis of YGTSS score reduction,social function impairment improvement,the clinical control rate,and long-term efficacy,the results were all Group A>Group B>Group C,with a statistically significant difference(P<0.05).However,the total clinical efficacy of treatment in group A(94.9%)was not significantly different from that in group B(91.8%).Adverse reactions did not occur in groups A and B,and several adverse reactions occurred in 29%(n=58)of the group C patients.CONCLUSION:Compared with traditional drug therapy,acupuncture combined with atlantoaxial joint bone setting therapy has better clinical and long-term efficacy.This treatment strategy can improve the social function of children and prevent adverse reactions to drugs.
