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
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
BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical ...BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.展开更多
This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical...This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical interventions forbone regeneration,particularly autogenic bone grafts,and discusses the exploration of alternative materials and methods,including allogeneic and xenogeneic bone grafts,synthetic materials,and biodegradable polymers.The objective is to provide a comprehensive understanding of how contemporary DDS can be optimized and integrated with tissue engineering approaches for more effective bone regeneration therapies.The review explained the mechanisms through which DDS enhance bone repair processes,identifies critical factors influencing their efficacy and safety,and offers an overview of current trends and future perspectives in the field.It emphasizes the need for advanced strategies in bone regeneration that focus on precise control of DDS to address bone conditions such as osteoporosis,trauma,and genetic predispositions leading to fractures.展开更多
BACKGROUND Giant cell tumor of bone(GCTB)is a rare,locally aggressive neoplasm that should be treated surgically,whenever possible.This treatment approach may be linked with greater morbidity besides functional impair...BACKGROUND Giant cell tumor of bone(GCTB)is a rare,locally aggressive neoplasm that should be treated surgically,whenever possible.This treatment approach may be linked with greater morbidity besides functional impairment.Denosumab is a human monoclonal antibody.Its administration inhibits bone resorption and has become part of the therapeutic armamentarium against GCTB,as it allows local control with a view to downstaging for a more conservative surgical procedure.However,there is no consensus in the literature regarding the optimal denosumab regimen for GCTB.Therefore,a wide discussion of denosumab regimen is necessary.AIM To assess the effectiveness of various therapy protocols employing denosumab in individuals with GCTB.METHODS A broad and systematic literature search was carried out using the PRISMA guidelines.We analyzed studies that reported skeletally mature patients with GCTB regardless of sex or ethnicity treated with denosumab.Articles with fewer than five patients and in languages except Spanish,Portuguese and English were excluded.Statistical analysis with proportion meta-analysis was performed due to the dichotomous nature of the data.RESULTS 1005 articles were screened,of which 26 articles met the inclusion criteria and were selected,totaling 1742 patients,51.8%women and 48.2%men,with an average of 35 years of age.Treatment with denosumab was associated with high rates of clinical benefit(CB)and imaging response(IR),without changing local recurrence rates when compared to patients treated without denosumab,regardless of the therapeutic regimen adopted and the number of doses applied.The adverse events(AE)presented were mostly mild,with the exception of a malignant transformation to osteosarcoma.CONCLUSION Treatment of GCTB with denosumab is effective,showing high rates of CB and IR.The AE that occurred were mostly mild.We found no differences between the articles considering the researched outcomes regardless of the therapeutic regimen adopted.展开更多
The global aging crisis has increased the prevalence of skeletal disorders,necessitating innovative therapeutic strategies.This review employs the brain-bone axis(BBA)framework to examine the role of the sympathetic n...The global aging crisis has increased the prevalence of skeletal disorders,necessitating innovative therapeutic strategies.This review employs the brain-bone axis(BBA)framework to examine the role of the sympathetic nervous system(SNS)in bone metabolism.The research systematically elucidates the molecular mechanisms by which the SNS mediates signaling pathways through neurofibers and neurotransmitters,such as norepinephrine,dopamine,neuropeptide Y,and leptin,regulating interactions between bone-related cells to maintain skeletal homeostasis.It also identifies the pathological associations between the dysregulation of these pathways and the progression of bone-related conditions,such as osteoporosis,osteoarthritis,and intervertebral disc degeneration.By integrating current evidence,we identify novel therapeutic targets within the BBA and propose neuro-centric intervention strategies to mitigate skeletal diseases.This review deepens the understanding of neuro-skeletal interactions and lays a foundation for innovative treatments for bone-related pathologies.展开更多
BACKGROUND Bone regeneration is a central focus of regenerative medicine,with applications in orthopedics and dentistry,particularly for treating bone defects caused by trauma,infection,or congenital anomalies.Synthet...BACKGROUND Bone regeneration is a central focus of regenerative medicine,with applications in orthopedics and dentistry,particularly for treating bone defects caused by trauma,infection,or congenital anomalies.Synthetic biomaterials,often combined with fibrin derivatives,offer promising solutions for bone healing and restoration.AIM To Explore the increasingly important role of the association of synthetic biomaterials with fibrin in bone regeneration.METHODS Search terms included:“synthetic biomaterials AND fibrin sealant”,“hydroxyapatite AND fibrin sealant”,“tricalcium phosphate AND fibrin sealant”,and“synthetic biomaterials AND platelet-rich fibrin(PRF)”,resulting in 67 articles.After rigorous screening,21 articles met the inclusion criteria.RESULTS The reviewed studies assessed biomaterials like hydroxyapatite(HA),β-tricalcium phosphate(β-TCP),and fibrin-based products.Key findings highlighted the enhanced osteoconductivity and biocompatibility of HA andβ-TCP,especially when combined with fibrin sealants.These composites show significant potential for improving cellular adhesion,promoting osteogenic differentiation,and accelerating bone regeneration.The antimicrobial properties and structural support for cell growth of certain biomaterials indicate a promising potential for clinical applic-ations.CONCLUSION This systematic review emphasizes the growing role of fibrin-based biomaterials in bone regeneration and urges continued research to improve their clinical use for complex bone defects.展开更多
Objective This systematic review examines recent pharmacoeconomic literature on denosumab'cost-effectiveness for bone metastasis treatment,providing evidence-based insights to guide healthcare policy decisions.Met...Objective This systematic review examines recent pharmacoeconomic literature on denosumab'cost-effectiveness for bone metastasis treatment,providing evidence-based insights to guide healthcare policy decisions.Methods A comprehensive literature search was performed across Cochrane,PubMed,EMBASE(Ovid),CNKI,and Wanfang databases to identify original articles published between 2017 and 2023.Key words consisted of bone metastases,denosumab,and cost-effectiveness in the search strategy.The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards(CHEERS 2022).Data was extracted regarding methodological characteristics and cost-effectiveness analyses.Results A total of 111 studies were retrieved,of which 6 met the inclusion criteria.All included studies were based on clinical trials and published literature data and exhibited high methodological quality.Up to 83%(5 out of 6)of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid.The adjusted incremental cost-effectiveness ratios varied substantially by tumor type,ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained.Conclusions The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid.The application of CHEER(2022)enhances the reliability of pharmacoeconomic evaluations.展开更多
Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databa...Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databases Reviewed:PubMed,Cochrane,Web of Science.Methods:Search terms utilized“temporal bone training”,“temporal bone surgical modalities”,and“training modalities temporal bone surgery”with“3D”,“rapid prototyp*”,“stereolithography”,“additive manufact*”,“plaster”,“VR”,“virtual reality”,“animal model”,“animal temporal bone”,and“synthetic”with“AND”for all literature.Exclusion criteria:non-ENT,non-English,and did not compare against alternative/traditional methods.Results:10 studies were included with 322 participants(83.9%ENT residents and 16.1%medical students).Costs include the FDM printer($300),materials($5/3D model),and<$5,000 for freeware simulator hardware.The Welling scale was used in 50%of studies.Alternate methods produced comparable or improved assessment scores to traditional and cadaver methods.Injuries were reported in three VR studies,with two reported significantly lower injury scores in the intervention groups.Time to completion was not significantly different in four VR studies,except for one finding that the time to visualize the incus was significantly lower in the intervention group.Performance after MP was not statistically different.Conclusion:More data are needed to assess whether the alternate methods are comparable to cadaveric dissection in temporal bone training.3D models and VR simulation demonstrate promising potential for novel trainees to acquire the basic skills and produce performance comparable to or significantly better than traditional methods of lectures,textbooks,CT images,and operative videos.展开更多
Objective To systematically evaluate the overall efficacy of external application of traditional Chinese medicine(EA-TCM)in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-...Objective To systematically evaluate the overall efficacy of external application of traditional Chinese medicine(EA-TCM)in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain(CIBP).Methods We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems.It included four Chinese databases[Chinese Biomedical Literature Database(SinoMed),China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(VIP)],six English databases(Scopus,Embase,Web of Science,PubMed,Cochrane Library,and OpenGrey),and two registration systems(Chinese Clinical Trial Registry and ClinicalTrials.gov).The timeframe for the literature search extended from the inception of each database to December 31,2023.Meta-analysis was performed using RevMan(v5.4.1),and the outcome indicators(pain relief rate,analgesic duration,quality of life,pain intensity,breakthrough pain frequency,and adverse reactions)were graded using GRADE profiler(v3.6).Results According to the established inclusion and exclusion criteria,a total of 43 studies was deemed eligible,involving 3142 participants with CIBP.The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone,the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate[risk ratio(RR)=1.32,95%confidence interval(CI):1.24 to 1.41,P<0.00001],analgesic duration[mean difference(MD)=1.33,95%CI:0.97 to 1.69,P<0.00001],and quality of life(MD=5.66,95%CI:4.88 to 6.44,P<0.00001).Furthermore,the combined therapy significantly reduced pain intensity(MD=-1.00,95%CI:-1.19 to-0.80,P<0.00001),breakthrough pain frequency(MD=-0.43,95%CI:-0.51 to-0.36,P<0.00001),and adverse reactions(RR=0.60,95%CI:0.53 to 0.68,P<0.00001)in CIBP patients.Based on the GRADE assessment,the level of evidence varied from low to moderate.Conclusion EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life.Additionally,the EA-TCM can effectively reduce the incidence of adverse reactions associated with threestep analgesic therapy.展开更多
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 Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clin...Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.展开更多
Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidit...Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.展开更多
Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation...Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.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
Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury...Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.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
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
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
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.
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.
文摘BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.
文摘This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical interventions forbone regeneration,particularly autogenic bone grafts,and discusses the exploration of alternative materials and methods,including allogeneic and xenogeneic bone grafts,synthetic materials,and biodegradable polymers.The objective is to provide a comprehensive understanding of how contemporary DDS can be optimized and integrated with tissue engineering approaches for more effective bone regeneration therapies.The review explained the mechanisms through which DDS enhance bone repair processes,identifies critical factors influencing their efficacy and safety,and offers an overview of current trends and future perspectives in the field.It emphasizes the need for advanced strategies in bone regeneration that focus on precise control of DDS to address bone conditions such as osteoporosis,trauma,and genetic predispositions leading to fractures.
文摘BACKGROUND Giant cell tumor of bone(GCTB)is a rare,locally aggressive neoplasm that should be treated surgically,whenever possible.This treatment approach may be linked with greater morbidity besides functional impairment.Denosumab is a human monoclonal antibody.Its administration inhibits bone resorption and has become part of the therapeutic armamentarium against GCTB,as it allows local control with a view to downstaging for a more conservative surgical procedure.However,there is no consensus in the literature regarding the optimal denosumab regimen for GCTB.Therefore,a wide discussion of denosumab regimen is necessary.AIM To assess the effectiveness of various therapy protocols employing denosumab in individuals with GCTB.METHODS A broad and systematic literature search was carried out using the PRISMA guidelines.We analyzed studies that reported skeletally mature patients with GCTB regardless of sex or ethnicity treated with denosumab.Articles with fewer than five patients and in languages except Spanish,Portuguese and English were excluded.Statistical analysis with proportion meta-analysis was performed due to the dichotomous nature of the data.RESULTS 1005 articles were screened,of which 26 articles met the inclusion criteria and were selected,totaling 1742 patients,51.8%women and 48.2%men,with an average of 35 years of age.Treatment with denosumab was associated with high rates of clinical benefit(CB)and imaging response(IR),without changing local recurrence rates when compared to patients treated without denosumab,regardless of the therapeutic regimen adopted and the number of doses applied.The adverse events(AE)presented were mostly mild,with the exception of a malignant transformation to osteosarcoma.CONCLUSION Treatment of GCTB with denosumab is effective,showing high rates of CB and IR.The AE that occurred were mostly mild.We found no differences between the articles considering the researched outcomes regardless of the therapeutic regimen adopted.
基金funded by Shaoxing University’s enterprise important horizontal topic(No.2024USXH287)the Graduate research project of Shaoxing University(Nos.Y20240280)。
文摘The global aging crisis has increased the prevalence of skeletal disorders,necessitating innovative therapeutic strategies.This review employs the brain-bone axis(BBA)framework to examine the role of the sympathetic nervous system(SNS)in bone metabolism.The research systematically elucidates the molecular mechanisms by which the SNS mediates signaling pathways through neurofibers and neurotransmitters,such as norepinephrine,dopamine,neuropeptide Y,and leptin,regulating interactions between bone-related cells to maintain skeletal homeostasis.It also identifies the pathological associations between the dysregulation of these pathways and the progression of bone-related conditions,such as osteoporosis,osteoarthritis,and intervertebral disc degeneration.By integrating current evidence,we identify novel therapeutic targets within the BBA and propose neuro-centric intervention strategies to mitigate skeletal diseases.This review deepens the understanding of neuro-skeletal interactions and lays a foundation for innovative treatments for bone-related pathologies.
文摘BACKGROUND Bone regeneration is a central focus of regenerative medicine,with applications in orthopedics and dentistry,particularly for treating bone defects caused by trauma,infection,or congenital anomalies.Synthetic biomaterials,often combined with fibrin derivatives,offer promising solutions for bone healing and restoration.AIM To Explore the increasingly important role of the association of synthetic biomaterials with fibrin in bone regeneration.METHODS Search terms included:“synthetic biomaterials AND fibrin sealant”,“hydroxyapatite AND fibrin sealant”,“tricalcium phosphate AND fibrin sealant”,and“synthetic biomaterials AND platelet-rich fibrin(PRF)”,resulting in 67 articles.After rigorous screening,21 articles met the inclusion criteria.RESULTS The reviewed studies assessed biomaterials like hydroxyapatite(HA),β-tricalcium phosphate(β-TCP),and fibrin-based products.Key findings highlighted the enhanced osteoconductivity and biocompatibility of HA andβ-TCP,especially when combined with fibrin sealants.These composites show significant potential for improving cellular adhesion,promoting osteogenic differentiation,and accelerating bone regeneration.The antimicrobial properties and structural support for cell growth of certain biomaterials indicate a promising potential for clinical applic-ations.CONCLUSION This systematic review emphasizes the growing role of fibrin-based biomaterials in bone regeneration and urges continued research to improve their clinical use for complex bone defects.
文摘Objective This systematic review examines recent pharmacoeconomic literature on denosumab'cost-effectiveness for bone metastasis treatment,providing evidence-based insights to guide healthcare policy decisions.Methods A comprehensive literature search was performed across Cochrane,PubMed,EMBASE(Ovid),CNKI,and Wanfang databases to identify original articles published between 2017 and 2023.Key words consisted of bone metastases,denosumab,and cost-effectiveness in the search strategy.The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards(CHEERS 2022).Data was extracted regarding methodological characteristics and cost-effectiveness analyses.Results A total of 111 studies were retrieved,of which 6 met the inclusion criteria.All included studies were based on clinical trials and published literature data and exhibited high methodological quality.Up to 83%(5 out of 6)of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid.The adjusted incremental cost-effectiveness ratios varied substantially by tumor type,ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained.Conclusions The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid.The application of CHEER(2022)enhances the reliability of pharmacoeconomic evaluations.
文摘Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databases Reviewed:PubMed,Cochrane,Web of Science.Methods:Search terms utilized“temporal bone training”,“temporal bone surgical modalities”,and“training modalities temporal bone surgery”with“3D”,“rapid prototyp*”,“stereolithography”,“additive manufact*”,“plaster”,“VR”,“virtual reality”,“animal model”,“animal temporal bone”,and“synthetic”with“AND”for all literature.Exclusion criteria:non-ENT,non-English,and did not compare against alternative/traditional methods.Results:10 studies were included with 322 participants(83.9%ENT residents and 16.1%medical students).Costs include the FDM printer($300),materials($5/3D model),and<$5,000 for freeware simulator hardware.The Welling scale was used in 50%of studies.Alternate methods produced comparable or improved assessment scores to traditional and cadaver methods.Injuries were reported in three VR studies,with two reported significantly lower injury scores in the intervention groups.Time to completion was not significantly different in four VR studies,except for one finding that the time to visualize the incus was significantly lower in the intervention group.Performance after MP was not statistically different.Conclusion:More data are needed to assess whether the alternate methods are comparable to cadaveric dissection in temporal bone training.3D models and VR simulation demonstrate promising potential for novel trainees to acquire the basic skills and produce performance comparable to or significantly better than traditional methods of lectures,textbooks,CT images,and operative videos.
基金Provincial Key Research and Development Project of Hunan(2018SK2127)Hunan Province Traditional Chinese Medicine Research and Development Project(201946).
文摘Objective To systematically evaluate the overall efficacy of external application of traditional Chinese medicine(EA-TCM)in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain(CIBP).Methods We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems.It included four Chinese databases[Chinese Biomedical Literature Database(SinoMed),China National Knowledge Infrastructure(CNKI),Wanfang Database,and China Science and Technology Journal Database(VIP)],six English databases(Scopus,Embase,Web of Science,PubMed,Cochrane Library,and OpenGrey),and two registration systems(Chinese Clinical Trial Registry and ClinicalTrials.gov).The timeframe for the literature search extended from the inception of each database to December 31,2023.Meta-analysis was performed using RevMan(v5.4.1),and the outcome indicators(pain relief rate,analgesic duration,quality of life,pain intensity,breakthrough pain frequency,and adverse reactions)were graded using GRADE profiler(v3.6).Results According to the established inclusion and exclusion criteria,a total of 43 studies was deemed eligible,involving 3142 participants with CIBP.The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone,the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate[risk ratio(RR)=1.32,95%confidence interval(CI):1.24 to 1.41,P<0.00001],analgesic duration[mean difference(MD)=1.33,95%CI:0.97 to 1.69,P<0.00001],and quality of life(MD=5.66,95%CI:4.88 to 6.44,P<0.00001).Furthermore,the combined therapy significantly reduced pain intensity(MD=-1.00,95%CI:-1.19 to-0.80,P<0.00001),breakthrough pain frequency(MD=-0.43,95%CI:-0.51 to-0.36,P<0.00001),and adverse reactions(RR=0.60,95%CI:0.53 to 0.68,P<0.00001)in CIBP patients.Based on the GRADE assessment,the level of evidence varied from low to moderate.Conclusion EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life.Additionally,the EA-TCM can effectively reduce the incidence of adverse reactions associated with threestep analgesic therapy.
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 Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.
基金performed as part of the cmRNAbone project funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement No 874790。
文摘Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.
基金supported by grant provided by the Sao Paulo Research Foundation-FAPESP.Grant#2023/15750-7。
文摘Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.
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supported by the Key Program of the National Natural Science Foundation of China(32230059)the Basic Science Center Program(T2288102)+3 种基金the Foundation of Frontiers Sciesnce Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the National Natural Science Foundation of China(32401128)the Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251)。
文摘Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.
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.
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.
