Background Tissue-engineering techniques combined with gene therapy have beenrecently reported to improve osteogenesis. In this study, tissue-engineered bone constructed byhuman Bone Morphogenetic Protein 4 (hBMP-4) g...Background Tissue-engineering techniques combined with gene therapy have beenrecently reported to improve osteogenesis. In this study, tissue-engineered bone constructed byhuman Bone Morphogenetic Protein 4 (hBMP-4) gene-modified bone marrow stromal cells (bMSCs) wasexplored in an ectopic bone formation model in rabbits. Methods A pEGFP-hBMP-4 mammalian plasmid (EGFP: Enhanced Green Fluorescent Protein) was constructed by subcloning techniques. bMSCs obtainedfrom rabbits were cultured and transfected with either pEGFP-hBMP-4, pEGFP or left uninfected invitro. Transfer efficiency was detected through the expression of EGFP. Transcription of the targetgene was detected by RT-PCR. Alkaline phosphatase (ALP) and Von Kossa tests were also conducted toexplore the phenotypes of osteoblasts. The autologous bMSCs of the 3 groups were then combined withNatural Non-organic Bone ( NNB) , a porous hydroxyapatite implant with a dimension of 6 mm x 6 mm x3 mm, at a concentration of 5 x 10~7 cells/ml. They were subsequently implanted into 6 rabbitssubcutaneously using NNB alone as a blank control (6 implants per group). Four weeks after surgery,the implants were evaluated with histological staining and computerized analysis of new boneformation. Results pEGFP-hBMP-4 expression plasmid was constructed. Under optimal conditions, genetransfer efficiency reached more than 30% , Target gene transfer could strengthen the transcriptionof BMP-4, and increase the expression of ALP as well as the number of calcium nodules. In theectopic animal model, NNB alone could not induce new bone formation. The new bone area formed in thebMSCs group was (17.2 ± 7.1)%, and pEGFP group was (14.7 ± 6.1) % , while pEGFP-hBMP-4 group was(29.5 ± 8.2) % , which was the highest among the groups (F = 7.295, P < 0. 01). Conclusions Themammalian hBMP-4 expression plasmid was successfully constructed and a comparatively high transferefficiency was achieved. The gene transfer technique enhanced the expression of BMP-4 and promoteddifferentiation from bMSCs to osteoblasts. These in vivo results suggested that transfection ofbMSCs with hBMP-4 might be a suitable method to enhance their inherent osteogenic capacity for bonetissue engineering applications.展开更多
Objective： A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapaUte （g-HA）/ poly（lactide-co-glycolide） （PLGA） carried with autologous mesenchymal stem cells （MSCs） and bone morphogene...Objective： A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapaUte （g-HA）/ poly（lactide-co-glycolide） （PLGA） carried with autologous mesenchymal stem cells （MSCs） and bone morphogenetic protein-2 （BMP-2） was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods： A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were ob- served by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results： After eight weeks post-surgery, scanning electron microscopy （SEM） and energy dispersive X-ray spectroscopy （EDX） revealed that g-HNPLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HNPLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HNPLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HNPLGA, while only fibrous tissues formed in PLGA. Conclusions： The incorporation of g-HA mainly im- proved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone for- mation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.展开更多
Background Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 （Nell-1）, a novel growth factor, has been reported to have specificity for ost...Background Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 （Nell-1）, a novel growth factor, has been reported to have specificity for osteochondral lineage. The study assessed the osteogenic differentiation of rat bone marrow stromal cells （bMSCs） after Nell-1 gene modification and examined its ectopic bone formation ability in a nude mice model with tissue engineering technique. Methods bMSCs obtained from Fischer 344 rats were transduced with either AdNell-1 （Nell-1 group） or Ad-β-galactosidase （AdLacZ, LacZ group） or left untransduced （untransduced group）. The expression of Nell-1 protein was determined by Western blotting and transfer efficiency was assessed, mRNA expressions of osteopontin （OP）, bone sialoprotein （BSP） and osteocalcin （OC） were assessed by real-time PCR 0, 3, 7, 14, and 21 days after gene transfer. Alkaline phosphatase （ALP） activity was measured and von Kossa test was also conducted. Finally, with a tissue engineering technique, gene transduced bMSCs, combining with β-tricalcium phosphate （β-TCP） at a concentration of 2×10^7 cells/ml, were implanted at subcutaneous sites on the back of nude mice. Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation. Results Under current transduction conditions, gene transfer efficiency reached （57.9±6.8）%. Nell-1 protein was detected in Nell-1 group but not in untransduced group and LacZ group. Induced by Nell-1, BSP and OP expression were increased at intermediate stage and OC expression was increased at later stage. ALP activity and the number of calcium nodules were highest in Nell-1 group. Four weeks after implanted into nude mice subcutaneously, the percentage of new bone area in Nell-1 group was （18.1±5.0）%, significantly higher than those of untransduced group （11.3±3.2）% and LacZ group （12.3±3.1）% （P〈0.05）. Conclusions This study has demonstrated the ability of Nell-1 to induce osteogenic differentiation of rat bMSCs in vitro and to enhance bone formation with a tissue engineering technique. The results suggest that Nell-1 may be a potential osteogenic gene to be used in bone tissue engineering.展开更多
Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts.Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetrat...Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts.Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds,enhanced production of bone marrow cells,and improved tissue-engineered bone formation.The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells （BMSCs）.Methods BMSCs/β-tricalcium phosphate （β-TCP） composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound （LIPUS） treatment group and a control group.These implants were harvested at 5,10,25,and 50 days after implantation.The samples were then biomechanically tested and analyzed for alkaline phosphate （ALP） activity and osteocalcin （OCN） content and were also observed by light microscopy.Results The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group.Histomorphometric analysis revealed a greater degree of soft tissue repair,increased blood flow,better angiogenesis,and more extensive bone formation in the LIPUS groups than in the controls.No significant difference in the compressive strength was found between the two groups.Conclusion LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β3-TCP composites.展开更多
BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological r...BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂展开更多
Objective To create a method for constructing a tissue-engineered graft with self-derived bone marrow cells and heterogeneous acellular matrix.Methods The mononuclear cells were isolated from bone marrows drawn from p...Objective To create a method for constructing a tissue-engineered graft with self-derived bone marrow cells and heterogeneous acellular matrix.Methods The mononuclear cells were isolated from bone marrows drawn from piglets and cultured in different mediums including either vascular endothelial growth factor(VEGF)or platelet derived growth factor BB(PDGF-BB)to observe their expansion and differentiation.The aortas harvested from canines were processed by a multi-step decellularizing technique to erase.The bone marrow mononuclear cells cultured in the mediums without any growth factors were seeded to the acellular matrix.The cells-seeded grafts were incubated in vitro for 6 d and then implanted to the cells-donated piglets to substitute parts of their native pulmonary arteries.Results After 4 d culturing,the cells incubated in the medium including VEGF showed morphological feature of endothelial cells(ECs)and were positive to ECs-specific monoclonal antibodies of CD31,FLK-1,VE-Cadherin and vWF.The cells incubated in the medium including PDGF-BB showed morphological feature of smooth muscle cells(SMCs)and were positive to SMCs-specific monoclonal antibodies of α-SMA and Calponin.One hundred days after implantation of seeded grafts,the inner surfaces of explants were smooth without thrombosis,calcification and aneurysm.Under the microscopy,plenty of growing cells could be seen and elastic and collagen fibers were abundant.Conclusion Mesenchymal stem cells might exist in mononuclear cells isolated from bone marrow.They would differentiate into endothelial cells or smooth muscle cells in proper in vitro or in vivo environments.The bone marrow mononuclear cells might be a choice of seeding cells in constructing tissue-engineered graft.展开更多
Background Currently used heart valve prostheses are associated with anticoagulation complications or limited durability. The advancement of stem cell study and tissue-engineered heart valve research may offer a relat...Background Currently used heart valve prostheses are associated with anticoagulation complications or limited durability. The advancement of stem cell study and tissue-engineered heart valve research may offer a relatively ideal solution to these problems. Methods Bone marrow was aspirated from sternum of lamb goats to isolate BMCs. Cells were identified by flow cytometry and its capacity of differentiation. Cellular viability was assessed with Rhdomine 123 staining. 1 × 10^7cells were seeded on a patch of PGA sheet. After two-day in vitro culture, autologous cell/ scaffold sheets were used to replace the right posterior pulmonary valve leaflets under cardiopulmonary bypass. The leaflets were explanted at 2 days, 2, 6, 8 and 10 weeks after implantation. The samples were examined macroscopically, histologically, immunohistochemically, and by Scanning Electron Microscope （SEM）. Two goats were implanted with acellular sheets and established as a control group. Results BMCs exhibited fibroblastoid morphology with good viability. Flow cytometry showed negative CD14 and CD45 expression. In vitro cultured BMCs demonstrated the potential to differentiate into adipocytes. The explanted leaflets resembled the characteristics of native extracellular matrix was leaflets macroscopicaIly in the cellular group. Histology showed synthesized and cells were distributed in the single-layered leaflets.Immunohistochemistry revealed positive staining for yon Willebrand factor, α-SMA, vimentin. A confluent cell surface was formed on the explanted TEHLs. No calcium deposited on the leaflets. In control group, the acellular scaffolds were completely degraded, without leaflet remained at 8 weeks. Conclusions It is possible to create tissue-engineered heart valves in vivo using autologous bone marrow-derived cells.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
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
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
Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective a...Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.展开更多
Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the orig...The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.展开更多
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relativ...Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation.While current anti-osteoporosis drugs,such as bisphosphonates and denosumab,predominantly focus on reducing bone resorption,osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk.Traditional Chinese medicines(TCMs)and their active ingredients have long been used in China for osteoporosis prevention and treatment.This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation.These compounds promote bone formation by regulating key transcription factors(RUNX2 and Osterix)and signaling pathways,including WNT/β-catenin,bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),oxidative stress,autophagy,and epigenetic regulation.Notably,certain natural products[e.g.,icariin(ICA)]exert their effects through multiple targets and pathways.Many of these natural products have demonstrated significant therapeutic efficacy in animal models,such as ovariectomized(OVX)mice.Our findings suggest that natural products with kidney-tonifying,anti-inflammatory,and antioxidant properties,as well as those inhibiting adipocyte differentiation,may hold promise for osteoporosis treatment.Additionally,we highlight current research gaps and propose future directions,including high-throughput screening and validation in diverse animal models,development of novel bone-targeting delivery systems,and identification of natural compounds targeting osteocytes.展开更多
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
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.展开更多
The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized...The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.展开更多
Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with ...Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.展开更多
文摘Background Tissue-engineering techniques combined with gene therapy have beenrecently reported to improve osteogenesis. In this study, tissue-engineered bone constructed byhuman Bone Morphogenetic Protein 4 (hBMP-4) gene-modified bone marrow stromal cells (bMSCs) wasexplored in an ectopic bone formation model in rabbits. Methods A pEGFP-hBMP-4 mammalian plasmid (EGFP: Enhanced Green Fluorescent Protein) was constructed by subcloning techniques. bMSCs obtainedfrom rabbits were cultured and transfected with either pEGFP-hBMP-4, pEGFP or left uninfected invitro. Transfer efficiency was detected through the expression of EGFP. Transcription of the targetgene was detected by RT-PCR. Alkaline phosphatase (ALP) and Von Kossa tests were also conducted toexplore the phenotypes of osteoblasts. The autologous bMSCs of the 3 groups were then combined withNatural Non-organic Bone ( NNB) , a porous hydroxyapatite implant with a dimension of 6 mm x 6 mm x3 mm, at a concentration of 5 x 10~7 cells/ml. They were subsequently implanted into 6 rabbitssubcutaneously using NNB alone as a blank control (6 implants per group). Four weeks after surgery,the implants were evaluated with histological staining and computerized analysis of new boneformation. Results pEGFP-hBMP-4 expression plasmid was constructed. Under optimal conditions, genetransfer efficiency reached more than 30% , Target gene transfer could strengthen the transcriptionof BMP-4, and increase the expression of ALP as well as the number of calcium nodules. In theectopic animal model, NNB alone could not induce new bone formation. The new bone area formed in thebMSCs group was (17.2 ± 7.1)%, and pEGFP group was (14.7 ± 6.1) % , while pEGFP-hBMP-4 group was(29.5 ± 8.2) % , which was the highest among the groups (F = 7.295, P < 0. 01). Conclusions Themammalian hBMP-4 expression plasmid was successfully constructed and a comparatively high transferefficiency was achieved. The gene transfer technique enhanced the expression of BMP-4 and promoteddifferentiation from bMSCs to osteoblasts. These in vivo results suggested that transfection ofbMSCs with hBMP-4 might be a suitable method to enhance their inherent osteogenic capacity for bonetissue engineering applications.
基金Project supported by the National Natural Science Foundation of China(Nos.51473164 and 51273195)the Joint Research Project of Chinese Academy of Sciences and Japan Society for the Promotion of Science(CAS-JSPS+1 种基金No.GJHZ1519)the International Science and Technology Cooperation Program of China(No.2014DFG52510)
文摘Objective： A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapaUte （g-HA）/ poly（lactide-co-glycolide） （PLGA） carried with autologous mesenchymal stem cells （MSCs） and bone morphogenetic protein-2 （BMP-2） was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods： A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were ob- served by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results： After eight weeks post-surgery, scanning electron microscopy （SEM） and energy dispersive X-ray spectroscopy （EDX） revealed that g-HNPLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HNPLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HNPLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HNPLGA, while only fibrous tissues formed in PLGA. Conclusions： The incorporation of g-HA mainly im- proved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone for- mation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.
基金This study was supported by grants from National Natural Science Foundation of China （No. 30400502 and 30772431）, Program for New Century Excellent Talents in University （NCET-08-0353）, Science and Technology Commission of Shanghai Municipality （No. 07DZ22007, 08410706400, 08JC1414400, and 08QH1401700）, Shanghai Rising-star Program （No. 05QMX1426）, and Shanghai Education Committee （No. 07SG 19）.
文摘Background Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 （Nell-1）, a novel growth factor, has been reported to have specificity for osteochondral lineage. The study assessed the osteogenic differentiation of rat bone marrow stromal cells （bMSCs） after Nell-1 gene modification and examined its ectopic bone formation ability in a nude mice model with tissue engineering technique. Methods bMSCs obtained from Fischer 344 rats were transduced with either AdNell-1 （Nell-1 group） or Ad-β-galactosidase （AdLacZ, LacZ group） or left untransduced （untransduced group）. The expression of Nell-1 protein was determined by Western blotting and transfer efficiency was assessed, mRNA expressions of osteopontin （OP）, bone sialoprotein （BSP） and osteocalcin （OC） were assessed by real-time PCR 0, 3, 7, 14, and 21 days after gene transfer. Alkaline phosphatase （ALP） activity was measured and von Kossa test was also conducted. Finally, with a tissue engineering technique, gene transduced bMSCs, combining with β-tricalcium phosphate （β-TCP） at a concentration of 2×10^7 cells/ml, were implanted at subcutaneous sites on the back of nude mice. Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation. Results Under current transduction conditions, gene transfer efficiency reached （57.9±6.8）%. Nell-1 protein was detected in Nell-1 group but not in untransduced group and LacZ group. Induced by Nell-1, BSP and OP expression were increased at intermediate stage and OC expression was increased at later stage. ALP activity and the number of calcium nodules were highest in Nell-1 group. Four weeks after implanted into nude mice subcutaneously, the percentage of new bone area in Nell-1 group was （18.1±5.0）%, significantly higher than those of untransduced group （11.3±3.2）% and LacZ group （12.3±3.1）% （P〈0.05）. Conclusions This study has demonstrated the ability of Nell-1 to induce osteogenic differentiation of rat bMSCs in vitro and to enhance bone formation with a tissue engineering technique. The results suggest that Nell-1 may be a potential osteogenic gene to be used in bone tissue engineering.
基金the National Natural Science Foundation of China，the Natural Science Foundation of Beijing,China
文摘Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts.Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds,enhanced production of bone marrow cells,and improved tissue-engineered bone formation.The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells （BMSCs）.Methods BMSCs/β-tricalcium phosphate （β-TCP） composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound （LIPUS） treatment group and a control group.These implants were harvested at 5,10,25,and 50 days after implantation.The samples were then biomechanically tested and analyzed for alkaline phosphate （ALP） activity and osteocalcin （OCN） content and were also observed by light microscopy.Results The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group.Histomorphometric analysis revealed a greater degree of soft tissue repair,increased blood flow,better angiogenesis,and more extensive bone formation in the LIPUS groups than in the controls.No significant difference in the compressive strength was found between the two groups.Conclusion LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β3-TCP composites.
基金Shanghai Municipal Natural Science Foundation,No.06ZR14108
文摘BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂
基金Supported by Shanghai Nature Science Foundation,China(99ZB14018)
文摘Objective To create a method for constructing a tissue-engineered graft with self-derived bone marrow cells and heterogeneous acellular matrix.Methods The mononuclear cells were isolated from bone marrows drawn from piglets and cultured in different mediums including either vascular endothelial growth factor(VEGF)or platelet derived growth factor BB(PDGF-BB)to observe their expansion and differentiation.The aortas harvested from canines were processed by a multi-step decellularizing technique to erase.The bone marrow mononuclear cells cultured in the mediums without any growth factors were seeded to the acellular matrix.The cells-seeded grafts were incubated in vitro for 6 d and then implanted to the cells-donated piglets to substitute parts of their native pulmonary arteries.Results After 4 d culturing,the cells incubated in the medium including VEGF showed morphological feature of endothelial cells(ECs)and were positive to ECs-specific monoclonal antibodies of CD31,FLK-1,VE-Cadherin and vWF.The cells incubated in the medium including PDGF-BB showed morphological feature of smooth muscle cells(SMCs)and were positive to SMCs-specific monoclonal antibodies of α-SMA and Calponin.One hundred days after implantation of seeded grafts,the inner surfaces of explants were smooth without thrombosis,calcification and aneurysm.Under the microscopy,plenty of growing cells could be seen and elastic and collagen fibers were abundant.Conclusion Mesenchymal stem cells might exist in mononuclear cells isolated from bone marrow.They would differentiate into endothelial cells or smooth muscle cells in proper in vitro or in vivo environments.The bone marrow mononuclear cells might be a choice of seeding cells in constructing tissue-engineered graft.
基金supported by the grant from Guangdong Nature Science Foundation(7001117)
文摘Background Currently used heart valve prostheses are associated with anticoagulation complications or limited durability. The advancement of stem cell study and tissue-engineered heart valve research may offer a relatively ideal solution to these problems. Methods Bone marrow was aspirated from sternum of lamb goats to isolate BMCs. Cells were identified by flow cytometry and its capacity of differentiation. Cellular viability was assessed with Rhdomine 123 staining. 1 × 10^7cells were seeded on a patch of PGA sheet. After two-day in vitro culture, autologous cell/ scaffold sheets were used to replace the right posterior pulmonary valve leaflets under cardiopulmonary bypass. The leaflets were explanted at 2 days, 2, 6, 8 and 10 weeks after implantation. The samples were examined macroscopically, histologically, immunohistochemically, and by Scanning Electron Microscope （SEM）. Two goats were implanted with acellular sheets and established as a control group. Results BMCs exhibited fibroblastoid morphology with good viability. Flow cytometry showed negative CD14 and CD45 expression. In vitro cultured BMCs demonstrated the potential to differentiate into adipocytes. The explanted leaflets resembled the characteristics of native extracellular matrix was leaflets macroscopicaIly in the cellular group. Histology showed synthesized and cells were distributed in the single-layered leaflets.Immunohistochemistry revealed positive staining for yon Willebrand factor, α-SMA, vimentin. A confluent cell surface was formed on the explanted TEHLs. No calcium deposited on the leaflets. In control group, the acellular scaffolds were completely degraded, without leaflet remained at 8 weeks. Conclusions It is possible to create tissue-engineered heart valves in vivo using autologous bone marrow-derived cells.
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Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
文摘The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.
基金supported by the National Natural Science Foundation of China(No.31800059)。
文摘Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation.While current anti-osteoporosis drugs,such as bisphosphonates and denosumab,predominantly focus on reducing bone resorption,osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk.Traditional Chinese medicines(TCMs)and their active ingredients have long been used in China for osteoporosis prevention and treatment.This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation.These compounds promote bone formation by regulating key transcription factors(RUNX2 and Osterix)and signaling pathways,including WNT/β-catenin,bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),oxidative stress,autophagy,and epigenetic regulation.Notably,certain natural products[e.g.,icariin(ICA)]exert their effects through multiple targets and pathways.Many of these natural products have demonstrated significant therapeutic efficacy in animal models,such as ovariectomized(OVX)mice.Our findings suggest that natural products with kidney-tonifying,anti-inflammatory,and antioxidant properties,as well as those inhibiting adipocyte differentiation,may hold promise for osteoporosis treatment.Additionally,we highlight current research gaps and propose future directions,including high-throughput screening and validation in diverse animal models,development of novel bone-targeting delivery systems,and identification of natural compounds targeting osteocytes.
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
基金supported by the National Natural Science Foundation of China (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
基金provided by the Joint Fund for Regional Innovation and Development(U23A20471)Beijing Natural Science Foundation(L242161,L241073,and 7232354)。
文摘The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.
文摘Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.
