BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment...BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.展开更多
AIM: To demonstrate that long head of the biceps tendon(LHBT) tenodesis is possible more than 3 mo after rupture. METHODS: From September 2009 to January 2012 we performed tenodesis of the LHBT in 11 individuals(avera...AIM: To demonstrate that long head of the biceps tendon(LHBT) tenodesis is possible more than 3 mo after rupture. METHODS: From September 2009 to January 2012 we performed tenodesis of the LHBT in 11 individuals(average age 56.9 years, range 42 to 73) more than 3 mo after rupture. All patients were evaluated by Disabilites of the Arm Shoulder and Hand(DASH) and Mayo outcome scores at an average follow-up of 19.1 mo. We similarly evaluated 5 patients(average age 58.2 years, range 45 to 64) over the same time treated within 3 mo of rupture with an average follow-up of 22.5 mo.RESULTS: Tenodesis with an interference screw was possible in all patients more than 3 mo after rupture and 90% had good to excellent outcomes but two had recurrent rupture. All of those who had tenodesis less than 3 mo after rupture had good to excellent outcomes and none had recurrent rupture. No statistical difference was found for DASH and Mayo outcome scores between the two groups(P <0.05). CONCLUSION: Tenodesis of LHBT more than 3 mo following rupture had outcomes similar to tenodesis done within 3 mo of rupture but recurrent rupture occurred in 20%.展开更多
Glucose metabolism is fundamental for the functions of all tissues,including cartilage.Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development,little is known ab...Glucose metabolism is fundamental for the functions of all tissues,including cartilage.Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development,little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis.We show here that genetic deletion of the glucose transporter Glutl in postnatal cartilage impairs cell proliferation and matrix production in growth plate(GPs)but paradoxically increases cartilage remnants in the metaphysis,resulting in shortening of long bones.On the other hand,articular cartilage(AC)with Glutl deficiency presents diminished cellularity and loss of proteoglycans,which ultimately progress to cartilage fibrosis.Moreover,predisposition to Glutl deficiency severely exacerbates injury-induced osteoarthritis.Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions,both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability.However,uncontrolled glutamine flux causes collagen overmodification,thus affecting extracellular matrix remodeling in both cartilage compartments.These results uncover the pivotal and distinct roles of Glutl-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.展开更多
Objective: To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids (EFs) regulate the balance between osteogenic differentiation and adipogenic differentiation in b...Objective: To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids (EFs) regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal ceils of ovariectomized rats, and to provide an experimental evidence for the mechanism of EFs on treating postmenopausal osteoporosis. Methods: Bone marrow stromal cells from ovariectomized rats were separated and cultivated in the condition of osteoinductive medium or liquid medium for 15 days. Low- (1 μg/mL), medium- (10 μg/mL) and high- (100 μg/mL) dose EFs were administrated correspondingly. Alkaline phosphatase (ALP) staining, ALP activity determination, oil red O staining and real- time polymerese chain reaction (RT-PCR) were used to determine the effect of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats. Moreover, in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats, Dickkopf-related protein 1 (DKK1) was used in the medium group. Enzyme linked immunosorbent assay (ELISA) and RT-PCR were used to determine mRNA levels of 13-catenin, low density lipoprotein receptor-related protein 5 (LRP5) and T cell factor (TCF) protein, known as wnt/β-catenin signal pathway related factors. Results: EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors, such as runt-related transcription factor 2 (Runx2), osteocaicin and collagen I, and decreased mRNA expression levels of fat generation factors, such as peroxisome proliferator activated receptor gamma 2 (PPAR r/-2) and CCAAT enhancer-binding protein-α (C/EBP α) in a dose-dependent manner. While osteobiast differentiation factors were down-regulated, fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of β-catenin, LRP5 and TCF protein which could be blocked by DKK1. Conclusion: EFs regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats by activating wnt/13-catenin signal pathway, which may be an important molecular mechanism of EFs on treatinq DostmenoDausal osteoDorosis.展开更多
OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin deficiency knee osteoarthritis(KOA).METHODS: One hundred patients were randomly divided into a treatment(50 patients) and control group(5...OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin deficiency knee osteoarthritis(KOA).METHODS: One hundred patients were randomly divided into a treatment(50 patients) and control group(50 patients). In the treatment group, patients orally took the Chinese medicine Huqian Wan. Control group patients orally took Votalin, 75 mg, once a day, for 8 weeks. The visual analog scale(VAS), Western Ontario and Mc Master University Osteoarthritis Index(WOMAC), and Medical Outcomes Study Short Form 36-Item Health Survey(SF36) were used to evaluate the curative effect before treatment and after 8 and 16 weeks of treatment.RESULTS: VAS and WOMAC scores significantly decreased and SF 36 scores significantly increased after treatment in both groups compared with before treatment(P < 0.05). There were significant differences in VAS, WOMAC, and SF 36 score changes between the two groups at week 16(P < 0.05).There was a significant increase in VAS and WOMAC scores in the control groups(P < 0.05) between weeks 8 and 16, but no significant difference was found in the treatment group(P > 0.05).CONCLUSION: Huqian Wan could effectively improve the clinical symptoms and quality of life in patients with KOA. It could also have a better and longer lasting curative effect without obvious adverse events compared with Votalin.展开更多
Ti–3Cu alloy has shown low melting point and strong antibacterial properties against S.aureus and E.coli and thus has potential application as dental materials and orthopedic application.In this paper, the corrosion ...Ti–3Cu alloy has shown low melting point and strong antibacterial properties against S.aureus and E.coli and thus has potential application as dental materials and orthopedic application.In this paper, the corrosion properties of Ti–3Cu alloy in five kinds of simulated solutions were investigated in comparison with cp-Ti(commercially pure titanium) by electrochemical technology and immersion experiment.Electrochemical results have demonstrated that Ti–3Cu alloy exhibited much nobler corrosion potential, lower corrosion current density and high corrosion resistance than cp-Ti in all solutions, especially in saliva-pH6.8+0.2 F and saliva-pH3.5, indicating that Ti–3Cu alloy has much better anticorrosion properties than cpTi.Immersion results have shown that Ti ion and Cu ion were released from Ti–3Cu, especially in saliva-pH6.8+0.2 F and saliva-pH3.5 solutions.Both electrochemical data and immersion results have indicated that high corrosion rate and high metal ion release rate were detected in F ion-containing solution and low-pH solution, displaying that F^- and low pH had much strong aggressive attack to cp-Ti and Ti–3Cu alloy.The corroded surface morphology was observed by scanning electron microscopy(SEM), and the roughness was tested in the end.The good corrosion resistance of antibacterial Ti–3Cu alloy suggests its great potential as a long-term biomedical application.展开更多
Ti-Cu alloy has potential to be used in plastic surgery and dental implants due to its strong antibacterialproperties,high strength and good corrosion resistance.In this paper,Ti-5Cu was anodic-oxidized to enhance the...Ti-Cu alloy has potential to be used in plastic surgery and dental implants due to its strong antibacterialproperties,high strength and good corrosion resistance.In this paper,Ti-5Cu was anodic-oxidized to enhance the surface compatibility.The influence of the oxidation on the corrosion resistance,antibacterial properties and biological properties was investigated.X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS)results showed that a double-layer oxide coating with dense inner layer and porous outside layer was formed on Ti-Cu sample.The oxide coating consisted mainly of TiO2,CuzO and small amount of CuO,improved the corrosion resistance of Ti-Cu alloy by one order of magnitude due to the formation of the dense oxide inner layer,but high Cu ion release was detected.The plate count results showed that the antibac-terial activity of Ti-Cu sample was improved to≥99%due to the comprehensive function of CuO and Cu_(2)O in the coating and Cu^(2+)release.Cell test results showed that thecoating exhibited good cell compatibility,the porous sur-face structure improved the adhesion of cells,and Cu ion release promoted the cell proliferation.展开更多
Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions.In this study,we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheum...Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions.In this study,we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis(RA).Arthritic mice displayed fracture nonunion with the absence of fracture callus,diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties,representing the major manifestations of atrophic nonunion in the clinic.Mechanistically,we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes,as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro.In this regard,we developed a biodegradable scaffold loaded with SPP1 and CXCL12,which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation.Hence,these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.展开更多
Objective: To observe the accuracy and the advantages and disadvantages of the femoral tunnels made by the two techniques. Materials and Methods: We randomly summoned nineteen patients undergoing anatomic ACL reconstr...Objective: To observe the accuracy and the advantages and disadvantages of the femoral tunnels made by the two techniques. Materials and Methods: We randomly summoned nineteen patients undergoing anatomic ACL reconstruction in a single band technique by the same surgeon: Ten by group II (GII) and nine by Group I (GI). GI: drilling in the technical in-out. GII: drilling the technique out-in. The patients underwent a CT scan with three-dimensional reconstruction of the distal femur. Was applied the technique of quadrants described by Bernard and Hertel and optimized for position by Forsythe and observed in the femoral tunnel: the accuracy of the joint entry;posterior cortical thickness in that point;emergency lateral distance to the lateral epicondyle and the overall length. Results: The coordinates of the distances obtained average was very close, with no statistical difference comparable to that obtained by Bernard and Hertel and Forsythe. The distance from the tunnel exit to the lateral epicondyle obtained average 1.46 cm in GI and 0.47 cm in GII, with a significant statistical difference. The thickness of the posterior cortex was 3.9 mm in GI and 5.4 mm in GII, with no statistical difference. The length averaged was 3.07 cm in GI and GII in 2.94 cm, with no statistical difference. Conclusions: Both techniques allow well placed tunnels, with no statistical difference. In the technique in-out the tunnel exit is closer to the lateral epicondyle. The thickness of the posterior cortex is similar. The length of the femoral tunnel is similar and around 3 cm.展开更多
Biomedical metals are widely used as implant materials in the human or animal body to repair organs and restore function, such as heart valves, meninges, peritoneum and artificial organs.Alloying element affects the m...Biomedical metals are widely used as implant materials in the human or animal body to repair organs and restore function, such as heart valves, meninges, peritoneum and artificial organs.Alloying element affects the microstructure, mechanical property, corrosion resistance and wear resistance, but also influences the antibacterial and biological activity.Recently, antibacterial metal alloys have shown great potential as a new kind of biomedical materials, in which Cu has been widely used as antibacterial agent element.In addition, biodegradable metal alloys, including magnesium alloy and zinc alloy, also have attracted much attention worldwide.Cu was also used as alloying element to adjust the degradation rate.Thus, the role of Cu in the alloy design will be very important for the development of new alloy.In this paper, we summarized the recent research results on the Cu-containing metal alloy for biomedical application and hoped that this review would give more suggestions for the further development of biomedical metal alloy.展开更多
The purpose of this experimental study was to explore the mechanism of the vertebral osteophyte formation. Methods: An experimental model of cervical spondylosis in rabbits was established by resection of the cervical...The purpose of this experimental study was to explore the mechanism of the vertebral osteophyte formation. Methods: An experimental model of cervical spondylosis in rabbits was established by resection of the cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from cervical vertebrae. Because of individual difference, the natural development procedure of the vertebral osteophyte formation could be seen with a microscope by dynamic observation. Results: The cartilage end-plate was divided into a growth cartilage layer and an articular cartilage layer. Vertebrae and discs from the 3-month control group rabbits showed normal structure. The changes of cartilage plates from the 3-month experimental group and the 8-month control group animals showed proliferation in peripheral articular cartilage. The osteophytes from the 8-month experimental group animals could be seen. The osteophyte obviously arised from proliferation, calcification and ossification of the peripheral articular cartilage. Conclusions: The vertebral osteophyte arises from proliferation of peripheral articular cartilage which undergoes cartilaginous osteophyte, and then changes into bony osteophyte through an endochondral calcification and ossification.展开更多
β-type titanium alloys have attracted much attention as implant materials because of their low elastic modulus and high strength,which is closer to human bones and can avoid the problem of stress fielding and extend ...β-type titanium alloys have attracted much attention as implant materials because of their low elastic modulus and high strength,which is closer to human bones and can avoid the problem of stress fielding and extend the lifetime of prosthetics.However,other issues,such as the infection or inflammation postimplantation,still trouble the titanium alloy's clinical application.In this paper,we developed a novel nearβ-titanium alloy(Ti-13Nb-13Zr-13Ag,TNZA)with low elastic modulus and strong antibacterial ability by the addition of Ag element followed by proper microstructure controlling,which could reduce the stress shielding and bacterial infections simultaneously.The microstructure,mechanical properties,corrosion resistance,antibacterial properties and cell toxicity were studied using SEM,electrochemical testing,mechanical test and cell tests.The results have demonstrated that TNZA alloy exhibited an elastic modulus of 75-87 GPa and a strong antibacterial ability(up to 98%reduction)and good biocompatibility.Moreover,it was also shown that this alloy's corrosion resistance was better than that of Ti-13Nb-13Zr.All the results suggested that Ti-13Nb-13Zr-13Ag might be a competitive biomedical titanium alloy.展开更多
Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics.However,most hydrogels offer limited cell growth and tissue formation ability due to the...Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics.However,most hydrogels offer limited cell growth and tissue formation ability due to their submicron-or nano-sized gel networks,which restrict the supply of oxygen,nutrients and inhibit the proliferation and differentiation of encapsulated cells.In recent years,3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds.In this study,we fabricated a macroporous hydrogel scaffold through horseradish peroxidase(HRP)-mediated crosslinking of silk fibroin(SF)and tyramine-substituted gelatin(GT)by extrusion-based low-temperature 3D printing.Through physicochemical characterization,we found that this hydrogel has excellent structural stability,suitable mechanical properties,and an adjustable degradation rate,thus satisfying the requirements for cartilage reconstruction.Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel.Moreover,the chondrogenic differentiation of stem cells was explored.Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used.Finally,the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model.After implantation for 12 and 16 weeks,histological evaluation of the sections was performed.We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration.In summary,this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.展开更多
Calcium phosphate cements(CPC)are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability,suitable to be used in minimally invasive treatment of bone defects....Calcium phosphate cements(CPC)are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability,suitable to be used in minimally invasive treatment of bone defects.However the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties,in particular its osteoinductivity.Hyaluronic acid reinforced calcium phosphate cements(HA/CPC)showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its osteoinductivity.In our study,the compressive strength of HA/CPC increased significantly when the cement was added 1%hyaluronic acid(denoted as 1-HA/CPC).In the meantime,hyaluronic acid obviously promoted ALP activity,osteogenic related protein and mRNA expression of hBMSCs(human bone marrow mesenchymal stem cells)in vitro,cement group of HA/CPC with 4%hyaluronic acid adding(denoted as 4-HA/CPC)showed optimal enhancement in hBMSCs differentiation.After being implanted in rat tibial defects,4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors,comparing to pure CPC and 1-HA/CPC groups.The underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid incorporation.These results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.展开更多
Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular...Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular nerve grafts(ANGs)with the aim of restoring long-distance peripheral nerve defects.Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4,Sox2,Klf4,and c-Myc.The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4,SSEA4,Nanog,Sox2,which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells(SCs)in vitro.After isolation and biological characteristics of iPSCs-derived exosomes,we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination.After that,we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats.Owing to the promotion of iPSCs-derived exosomes,satisfactory regenerative outcomes were achieved including gait behavior analysis,electrophysiological assessment,and morphological analysis of regenerated nerves.Especially,motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers.Taken together,our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects,and thus represents a cell-free strategy for future clinical applications.展开更多
It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflamm...It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials.展开更多
The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive materials.He...The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive materials.Here,the transcriptional landscapes of different osteogenic microenvironments,including three-dimensional(3D)hydroxyapatite(HA)scaffolds and osteogenic medium(OM),for mesenchymal stromal cells(MSCs)in vitro were mapped at single-cell resolution.Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways,along with inflammation and angiogenesis,but inhibition of adipogenesis and fibrosis.Moreover,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways.Heterogeneity of MSCs was also demonstrated.In vitro ossification of LRRC75A+MSCs was shown to have better utilization of WNT-related ossification process,and PCDH10+MSCs with superiority in hydroxyapatite-related osteogenic process.These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic biomaterials.This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration.展开更多
There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capac...There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo.However,the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined.In this study,bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr(0 mol%to 12 mol%SrO)were created and evaluated in vitro and in vivo.The setting time of the cement increased with Sr substitution of the glass.Upon immersion in PBS,the cement degraded and converted more slowly to HA(hydroxyapatite)with increasing Sr substitution.The released Sr2+modulated the proliferation,differentiation,and mineralization of hBMSCs(human bone marrow mesenchymal stem cells)in vitro.Osteogenic characteristics were optimally enhanced with cement(designated BG6Sr)composed of particles substituted with 6mol%SrO.When implanted in rabbit femoral condyle defects,BG6Sr cement supported better peri-implant bone formation and bone-implant contact,comparing to cements substituted with 0mol%or 9mol%SrO.The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs.These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.展开更多
The daily life of people in the intelligent age is inseparable from electronic device,and a number of bacteria on touch screens are increasingly threatening the health of users.Herein,a photocatalytic TiO_(2)/Ag thin ...The daily life of people in the intelligent age is inseparable from electronic device,and a number of bacteria on touch screens are increasingly threatening the health of users.Herein,a photocatalytic TiO_(2)/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction.Ultraviolet-visible(UV-Vis)spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO_(2).The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO_(2)/Ag film against S.aureus and E.coli was 98.2%and 98.6%,under visible light irradiation for 5 min.The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO_(2)reduced the bandgap of TiO_(2)from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO_(2)and Ag.Thus,TiO_(2)/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens.More importantly,the TiO_(2)/Ag film had great biocompatibility with/without light irradiation.The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.展开更多
The authors regret that the printed version of the above article contained a number of errors which were not identified during the proofing stage.The correct and final version follows.The authors would like to apologi...The authors regret that the printed version of the above article contained a number of errors which were not identified during the proofing stage.The correct and final version follows.The authors would like to apologies for any inconvenience caused.The authors regret:1.“…and the underlying molecular mechanism of this simulation is yet to be determined”,Page 335,needs to be corrected to“and the underlying molecular mechanism of this stimulation is yet to be determined”.展开更多
基金the National Natural Science Foundation of China,No.82274547the Major Program of the National Natural Science Foundation of Zhejiang Province,No.LD22C060002+1 种基金the State Administration of Traditional Chinese Medicine of Zhejiang Province,No.GZY-ZJ-KJ-23064the Zhejiang Provincial Research Foundation for Basic Public Welfare Research,No.LGF20H270005.
文摘BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.
文摘AIM: To demonstrate that long head of the biceps tendon(LHBT) tenodesis is possible more than 3 mo after rupture. METHODS: From September 2009 to January 2012 we performed tenodesis of the LHBT in 11 individuals(average age 56.9 years, range 42 to 73) more than 3 mo after rupture. All patients were evaluated by Disabilites of the Arm Shoulder and Hand(DASH) and Mayo outcome scores at an average follow-up of 19.1 mo. We similarly evaluated 5 patients(average age 58.2 years, range 45 to 64) over the same time treated within 3 mo of rupture with an average follow-up of 22.5 mo.RESULTS: Tenodesis with an interference screw was possible in all patients more than 3 mo after rupture and 90% had good to excellent outcomes but two had recurrent rupture. All of those who had tenodesis less than 3 mo after rupture had good to excellent outcomes and none had recurrent rupture. No statistical difference was found for DASH and Mayo outcome scores between the two groups(P <0.05). CONCLUSION: Tenodesis of LHBT more than 3 mo following rupture had outcomes similar to tenodesis done within 3 mo of rupture but recurrent rupture occurred in 20%.
基金This work was supported by the following NIH/NIAMS grants:R01 grants(AR069605 and AR079100 to RJ.O.as well as AR075860 and AR077616 to J.S.),an R21 grant(AR077226 to J.S.),a P30 Core Center grant(AR057235 to Musculoskeletal Research Center)an NCI grant(R35ES028365 to G.P.).
文摘Glucose metabolism is fundamental for the functions of all tissues,including cartilage.Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development,little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis.We show here that genetic deletion of the glucose transporter Glutl in postnatal cartilage impairs cell proliferation and matrix production in growth plate(GPs)but paradoxically increases cartilage remnants in the metaphysis,resulting in shortening of long bones.On the other hand,articular cartilage(AC)with Glutl deficiency presents diminished cellularity and loss of proteoglycans,which ultimately progress to cartilage fibrosis.Moreover,predisposition to Glutl deficiency severely exacerbates injury-induced osteoarthritis.Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions,both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability.However,uncontrolled glutamine flux causes collagen overmodification,thus affecting extracellular matrix remodeling in both cartilage compartments.These results uncover the pivotal and distinct roles of Glutl-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.
文摘Objective: To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids (EFs) regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal ceils of ovariectomized rats, and to provide an experimental evidence for the mechanism of EFs on treating postmenopausal osteoporosis. Methods: Bone marrow stromal cells from ovariectomized rats were separated and cultivated in the condition of osteoinductive medium or liquid medium for 15 days. Low- (1 μg/mL), medium- (10 μg/mL) and high- (100 μg/mL) dose EFs were administrated correspondingly. Alkaline phosphatase (ALP) staining, ALP activity determination, oil red O staining and real- time polymerese chain reaction (RT-PCR) were used to determine the effect of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats. Moreover, in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats, Dickkopf-related protein 1 (DKK1) was used in the medium group. Enzyme linked immunosorbent assay (ELISA) and RT-PCR were used to determine mRNA levels of 13-catenin, low density lipoprotein receptor-related protein 5 (LRP5) and T cell factor (TCF) protein, known as wnt/β-catenin signal pathway related factors. Results: EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors, such as runt-related transcription factor 2 (Runx2), osteocaicin and collagen I, and decreased mRNA expression levels of fat generation factors, such as peroxisome proliferator activated receptor gamma 2 (PPAR r/-2) and CCAAT enhancer-binding protein-α (C/EBP α) in a dose-dependent manner. While osteobiast differentiation factors were down-regulated, fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of β-catenin, LRP5 and TCF protein which could be blocked by DKK1. Conclusion: EFs regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats by activating wnt/13-catenin signal pathway, which may be an important molecular mechanism of EFs on treatinq DostmenoDausal osteoDorosis.
基金Supported by Major Special Sci-tech Projects of Zhejiang Province(Study on the Early Diagnosis of Osteoarthritis and Intervention of Traditional Chinese Medicine,No.2012C13017-2)the Program for Zhejiang Leading Team of S&T Innovation(Role of Mmp13 and Admats5 in the TGF-βSignaling Pathway and Pathogenesis of Osteoarthritis,No.2011R50022-01)Key Laboratory of Zhejiang Province(Chinese Medicine Intervention for Bone and Joint Diseases,No.2013E10024)
文摘OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin deficiency knee osteoarthritis(KOA).METHODS: One hundred patients were randomly divided into a treatment(50 patients) and control group(50 patients). In the treatment group, patients orally took the Chinese medicine Huqian Wan. Control group patients orally took Votalin, 75 mg, once a day, for 8 weeks. The visual analog scale(VAS), Western Ontario and Mc Master University Osteoarthritis Index(WOMAC), and Medical Outcomes Study Short Form 36-Item Health Survey(SF36) were used to evaluate the curative effect before treatment and after 8 and 16 weeks of treatment.RESULTS: VAS and WOMAC scores significantly decreased and SF 36 scores significantly increased after treatment in both groups compared with before treatment(P < 0.05). There were significant differences in VAS, WOMAC, and SF 36 score changes between the two groups at week 16(P < 0.05).There was a significant increase in VAS and WOMAC scores in the control groups(P < 0.05) between weeks 8 and 16, but no significant difference was found in the treatment group(P > 0.05).CONCLUSION: Huqian Wan could effectively improve the clinical symptoms and quality of life in patients with KOA. It could also have a better and longer lasting curative effect without obvious adverse events compared with Votalin.
基金financially supported by the National Natural Science Foundation of China (Nos.81071262 and 31271024)the Funding from Northeastern University, China (Nos.N141008001 and LZ2014018)Beijing Municipal Natural Science Foundation (No.7161001)
文摘Ti–3Cu alloy has shown low melting point and strong antibacterial properties against S.aureus and E.coli and thus has potential application as dental materials and orthopedic application.In this paper, the corrosion properties of Ti–3Cu alloy in five kinds of simulated solutions were investigated in comparison with cp-Ti(commercially pure titanium) by electrochemical technology and immersion experiment.Electrochemical results have demonstrated that Ti–3Cu alloy exhibited much nobler corrosion potential, lower corrosion current density and high corrosion resistance than cp-Ti in all solutions, especially in saliva-pH6.8+0.2 F and saliva-pH3.5, indicating that Ti–3Cu alloy has much better anticorrosion properties than cpTi.Immersion results have shown that Ti ion and Cu ion were released from Ti–3Cu, especially in saliva-pH6.8+0.2 F and saliva-pH3.5 solutions.Both electrochemical data and immersion results have indicated that high corrosion rate and high metal ion release rate were detected in F ion-containing solution and low-pH solution, displaying that F^- and low pH had much strong aggressive attack to cp-Ti and Ti–3Cu alloy.The corroded surface morphology was observed by scanning electron microscopy(SEM), and the roughness was tested in the end.The good corrosion resistance of antibacterial Ti–3Cu alloy suggests its great potential as a long-term biomedical application.
基金This work was financially supported by the National Natural Science Foundation of China(No.31971253)Beijing Municipal Health Commission(Nos.BMHC-2019-9,BMHC-2018-4 and PXM2020-026275-000002).
文摘Ti-Cu alloy has potential to be used in plastic surgery and dental implants due to its strong antibacterialproperties,high strength and good corrosion resistance.In this paper,Ti-5Cu was anodic-oxidized to enhance the surface compatibility.The influence of the oxidation on the corrosion resistance,antibacterial properties and biological properties was investigated.X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS)results showed that a double-layer oxide coating with dense inner layer and porous outside layer was formed on Ti-Cu sample.The oxide coating consisted mainly of TiO2,CuzO and small amount of CuO,improved the corrosion resistance of Ti-Cu alloy by one order of magnitude due to the formation of the dense oxide inner layer,but high Cu ion release was detected.The plate count results showed that the antibac-terial activity of Ti-Cu sample was improved to≥99%due to the comprehensive function of CuO and Cu_(2)O in the coating and Cu^(2+)release.Cell test results showed that thecoating exhibited good cell compatibility,the porous sur-face structure improved the adhesion of cells,and Cu ion release promoted the cell proliferation.
基金supported by the following NIH/NIAMS grants:R01 grants(AR075860 and AR077616 to J.S.,AR072623 and AR049192 to Y.A.EB022018,HL138175,HL138353,AG056919,and AR077616 to J.G.),an R21 grant(AR077226 to J.S.),a P30 Core Center grant(AR074992 to the Musculoskeletal Research Center)a biomedical grant from Shriners Hospital for Children(#85160 to Y.A.).
文摘Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions.In this study,we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis(RA).Arthritic mice displayed fracture nonunion with the absence of fracture callus,diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties,representing the major manifestations of atrophic nonunion in the clinic.Mechanistically,we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes,as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro.In this regard,we developed a biodegradable scaffold loaded with SPP1 and CXCL12,which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation.Hence,these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.
文摘Objective: To observe the accuracy and the advantages and disadvantages of the femoral tunnels made by the two techniques. Materials and Methods: We randomly summoned nineteen patients undergoing anatomic ACL reconstruction in a single band technique by the same surgeon: Ten by group II (GII) and nine by Group I (GI). GI: drilling in the technical in-out. GII: drilling the technique out-in. The patients underwent a CT scan with three-dimensional reconstruction of the distal femur. Was applied the technique of quadrants described by Bernard and Hertel and optimized for position by Forsythe and observed in the femoral tunnel: the accuracy of the joint entry;posterior cortical thickness in that point;emergency lateral distance to the lateral epicondyle and the overall length. Results: The coordinates of the distances obtained average was very close, with no statistical difference comparable to that obtained by Bernard and Hertel and Forsythe. The distance from the tunnel exit to the lateral epicondyle obtained average 1.46 cm in GI and 0.47 cm in GII, with a significant statistical difference. The thickness of the posterior cortex was 3.9 mm in GI and 5.4 mm in GII, with no statistical difference. The length averaged was 3.07 cm in GI and GII in 2.94 cm, with no statistical difference. Conclusions: Both techniques allow well placed tunnels, with no statistical difference. In the technique in-out the tunnel exit is closer to the lateral epicondyle. The thickness of the posterior cortex is similar. The length of the femoral tunnel is similar and around 3 cm.
基金financially supported by the National Natural Science Foundation of China (Nos.81071262 and 31470930)the Beijing Municipal Natural Science Foundation (No.7161001)
文摘Biomedical metals are widely used as implant materials in the human or animal body to repair organs and restore function, such as heart valves, meninges, peritoneum and artificial organs.Alloying element affects the microstructure, mechanical property, corrosion resistance and wear resistance, but also influences the antibacterial and biological activity.Recently, antibacterial metal alloys have shown great potential as a new kind of biomedical materials, in which Cu has been widely used as antibacterial agent element.In addition, biodegradable metal alloys, including magnesium alloy and zinc alloy, also have attracted much attention worldwide.Cu was also used as alloying element to adjust the degradation rate.Thus, the role of Cu in the alloy design will be very important for the development of new alloy.In this paper, we summarized the recent research results on the Cu-containing metal alloy for biomedical application and hoped that this review would give more suggestions for the further development of biomedical metal alloy.
文摘The purpose of this experimental study was to explore the mechanism of the vertebral osteophyte formation. Methods: An experimental model of cervical spondylosis in rabbits was established by resection of the cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from cervical vertebrae. Because of individual difference, the natural development procedure of the vertebral osteophyte formation could be seen with a microscope by dynamic observation. Results: The cartilage end-plate was divided into a growth cartilage layer and an articular cartilage layer. Vertebrae and discs from the 3-month control group rabbits showed normal structure. The changes of cartilage plates from the 3-month experimental group and the 8-month control group animals showed proliferation in peripheral articular cartilage. The osteophytes from the 8-month experimental group animals could be seen. The osteophyte obviously arised from proliferation, calcification and ossification of the peripheral articular cartilage. Conclusions: The vertebral osteophyte arises from proliferation of peripheral articular cartilage which undergoes cartilaginous osteophyte, and then changes into bony osteophyte through an endochondral calcification and ossification.
基金The authors would like to acknowledge the financial support from the National Natural Science Foundation of China(Nos.31971253)the Beijing Municipal Health Commission(Nos.BMHC-2019-9,BMHC-2018-4 and PXM2020_026275_000002)。
文摘β-type titanium alloys have attracted much attention as implant materials because of their low elastic modulus and high strength,which is closer to human bones and can avoid the problem of stress fielding and extend the lifetime of prosthetics.However,other issues,such as the infection or inflammation postimplantation,still trouble the titanium alloy's clinical application.In this paper,we developed a novel nearβ-titanium alloy(Ti-13Nb-13Zr-13Ag,TNZA)with low elastic modulus and strong antibacterial ability by the addition of Ag element followed by proper microstructure controlling,which could reduce the stress shielding and bacterial infections simultaneously.The microstructure,mechanical properties,corrosion resistance,antibacterial properties and cell toxicity were studied using SEM,electrochemical testing,mechanical test and cell tests.The results have demonstrated that TNZA alloy exhibited an elastic modulus of 75-87 GPa and a strong antibacterial ability(up to 98%reduction)and good biocompatibility.Moreover,it was also shown that this alloy's corrosion resistance was better than that of Ti-13Nb-13Zr.All the results suggested that Ti-13Nb-13Zr-13Ag might be a competitive biomedical titanium alloy.
基金This work was financially supported by the National Natural Science Foundation of China(Grant nos.52073103,51873069 and 51873071)the National Key R&D Program of China(Grant No.2018YFC1106300)+1 种基金Beijing Municipal Health Commission(Grant nos.BMHC-2019-9,BMHC-2018-4 and PXM2020_026275_000002)the funds for Zhongshan Innovation Project of high-end Scientific Research Institutions(Grant No.2020AG020).
文摘Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics.However,most hydrogels offer limited cell growth and tissue formation ability due to their submicron-or nano-sized gel networks,which restrict the supply of oxygen,nutrients and inhibit the proliferation and differentiation of encapsulated cells.In recent years,3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds.In this study,we fabricated a macroporous hydrogel scaffold through horseradish peroxidase(HRP)-mediated crosslinking of silk fibroin(SF)and tyramine-substituted gelatin(GT)by extrusion-based low-temperature 3D printing.Through physicochemical characterization,we found that this hydrogel has excellent structural stability,suitable mechanical properties,and an adjustable degradation rate,thus satisfying the requirements for cartilage reconstruction.Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel.Moreover,the chondrogenic differentiation of stem cells was explored.Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used.Finally,the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model.After implantation for 12 and 16 weeks,histological evaluation of the sections was performed.We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration.In summary,this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.
基金the National Key R&D Program of China(Grant No.2018YFC1106300 and 2017YFC1105000)the National Natural Science Foundation of China(Grant No.52072398,51802340,31870956,81860385,81672227,U2001221,51772210)+2 种基金the Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)the Shenzhen Significant Strategy Layout Project(Grant No.JCYJ20170413162104773 and JCYJ20200109114620793)Beijing Municipal Health Commission(Grant No.BMHC-2018-4,BMHC-2019-9,PXM2020_026275_000002).
文摘Calcium phosphate cements(CPC)are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability,suitable to be used in minimally invasive treatment of bone defects.However the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties,in particular its osteoinductivity.Hyaluronic acid reinforced calcium phosphate cements(HA/CPC)showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its osteoinductivity.In our study,the compressive strength of HA/CPC increased significantly when the cement was added 1%hyaluronic acid(denoted as 1-HA/CPC).In the meantime,hyaluronic acid obviously promoted ALP activity,osteogenic related protein and mRNA expression of hBMSCs(human bone marrow mesenchymal stem cells)in vitro,cement group of HA/CPC with 4%hyaluronic acid adding(denoted as 4-HA/CPC)showed optimal enhancement in hBMSCs differentiation.After being implanted in rat tibial defects,4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors,comparing to pure CPC and 1-HA/CPC groups.The underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid incorporation.These results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.
基金supported in part by the National Natural Science Foundation of China of China(Contract Grant No.81702133,81802144)the Research Project of Shanghai Municipal Health Commission(Contract Grant No.20194Y0316)Excellent Youth Training Program of Shanghai Jiaotong University Affiliated Sixth People’s Hospital(Contract Grant No.ynyq202102).
文摘Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular nerve grafts(ANGs)with the aim of restoring long-distance peripheral nerve defects.Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4,Sox2,Klf4,and c-Myc.The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4,SSEA4,Nanog,Sox2,which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells(SCs)in vitro.After isolation and biological characteristics of iPSCs-derived exosomes,we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination.After that,we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats.Owing to the promotion of iPSCs-derived exosomes,satisfactory regenerative outcomes were achieved including gait behavior analysis,electrophysiological assessment,and morphological analysis of regenerated nerves.Especially,motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers.Taken together,our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects,and thus represents a cell-free strategy for future clinical applications.
基金This research was supported by the National Natural Science Foundation of China(Grant no.32071351,81772400 and 31900583,32071341)the Fundamental Research Funds for the Central Universities(Grant no.19ykzd05)+3 种基金the Committee for Science and Technology Innovation of Shenzhen(Grant no.JCYJ20190809142211354 and GJHZ20180929160004704)the Sanming Project of Medicine in Shenzhen(Grant no.SZSM201911002)the Natural Science Foundation of Guangzhou City(Grant no.201807010031,201704030082)the Beijing Municipal Health Commission(Grant no.BMHC-2019-9,BMHC-2018-4,PXM2020_026275_000002).
文摘It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials.
基金This study was supported by the National Key R&D Program of China(Grant no.2017YFC1105000)the National Natural Science Foundation of China(Grant no.81772400,31900583,31430030)+4 种基金the Fundamental Research Funds for the Central Universities(Grant no.19ykzd05)the Natural Science Foundation of Guangzhou City(Grant no.201704030082,201807010031)the Foundation of Shenzhen Committee for Science and Technology Innovation(Grant no.JCYJ20190809142211354,GJHZ20180929160004704)the Sanming Project of Medicine in Shenzhen(Grant no.SZSM201911002)and the Beijing Municipal Health Commission(Grant no.BMHC-2021-X,BMHC-2019-9,BMHC-2018-4,PXM2020_026275_000002).Special thanks are extended to Dr.Cheng Ruijuan for technical support.
文摘The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive materials.Here,the transcriptional landscapes of different osteogenic microenvironments,including three-dimensional(3D)hydroxyapatite(HA)scaffolds and osteogenic medium(OM),for mesenchymal stromal cells(MSCs)in vitro were mapped at single-cell resolution.Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways,along with inflammation and angiogenesis,but inhibition of adipogenesis and fibrosis.Moreover,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways.Heterogeneity of MSCs was also demonstrated.In vitro ossification of LRRC75A+MSCs was shown to have better utilization of WNT-related ossification process,and PCDH10+MSCs with superiority in hydroxyapatite-related osteogenic process.These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic biomaterials.This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration.
基金supported by the National Key R&D Program of China(Grant No.2018YFC1106300 , 2017YFC1105000)the National Natural Science Foundation of China(Grant No.51802340,31870956,31771041 , 81672227)+6 种基金the Science and Technology Project of Guangdong Province-Doctoral startup fund of 2017(Grant No.2017A030310318)the Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)the Strategic Priority Research Program of CAS(Grant No.XDA16021000)the Shenzhen significant strategy layout project(Grant No.JCYJ20170413162104773)the Economic,Trade and information Commission of Shenzhen Municipality“Innovation and Industry Chain”(Grant No.20170502171625936)the Beijing Municipal Natural Science Foundation(Grant No.7161001)Beijing Municipal Commission of Health and Family Planning(Grant No.PXM2018_026275_000001).
文摘There is a need for synthetic grafts to reconstruct large bone defects using minimal invasive surgery.Our previous study showed that incorporation of Sr into bioactive borate glass cement enhanced the osteogenic capacity in vivo.However,the amount of Sr in the cement to provide an optimal combination of physicochemical properties and capacity to stimulate bone regeneration and the underlying molecular mechanism of this stimulation is yet to be determined.In this study,bone cements composed of bioactive borosilicate glass particles substituted with varying amounts of Sr(0 mol%to 12 mol%SrO)were created and evaluated in vitro and in vivo.The setting time of the cement increased with Sr substitution of the glass.Upon immersion in PBS,the cement degraded and converted more slowly to HA(hydroxyapatite)with increasing Sr substitution.The released Sr2+modulated the proliferation,differentiation,and mineralization of hBMSCs(human bone marrow mesenchymal stem cells)in vitro.Osteogenic characteristics were optimally enhanced with cement(designated BG6Sr)composed of particles substituted with 6mol%SrO.When implanted in rabbit femoral condyle defects,BG6Sr cement supported better peri-implant bone formation and bone-implant contact,comparing to cements substituted with 0mol%or 9mol%SrO.The underlying mechanism is involved in the activation of Wnt/β-catenin signaling pathway in osteogenic differentiation of hBMSCs.These results indicate that BG6Sr cement has a promising combination of physicochemical properties and biological performance for minimally invasive healing of bone defects.
基金financially supported by the National Natural Science Foundation of China(Nos.82002303,51871162 and 51932002)the China National Funds for Distinguished Young Scientists(No.51925104)+2 种基金Scientific Research Foundation of Peking University Shenzhen Hospital(No.KYQD2021064)Beijing Municipal Health Commission(Nos.BMHC-2021-6,BMHC-2019-9,BMHC-2018-4 and PXM2020_026275_000002)the National Key R&D Program of China(No.R&D#2018YFA0703100)
文摘The daily life of people in the intelligent age is inseparable from electronic device,and a number of bacteria on touch screens are increasingly threatening the health of users.Herein,a photocatalytic TiO_(2)/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction.Ultraviolet-visible(UV-Vis)spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO_(2).The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO_(2)/Ag film against S.aureus and E.coli was 98.2%and 98.6%,under visible light irradiation for 5 min.The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO_(2)reduced the bandgap of TiO_(2)from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO_(2)and Ag.Thus,TiO_(2)/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens.More importantly,the TiO_(2)/Ag film had great biocompatibility with/without light irradiation.The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.
文摘The authors regret that the printed version of the above article contained a number of errors which were not identified during the proofing stage.The correct and final version follows.The authors would like to apologies for any inconvenience caused.The authors regret:1.“…and the underlying molecular mechanism of this simulation is yet to be determined”,Page 335,needs to be corrected to“and the underlying molecular mechanism of this stimulation is yet to be determined”.