In this paper, we develop a hybrid model based on SCOR and BPMN to model the operational processes of a platform of cross docking. The interest of the developed model is its dynamic capacity to describe the interactio...In this paper, we develop a hybrid model based on SCOR and BPMN to model the operational processes of a platform of cross docking. The interest of the developed model is its dynamic capacity to describe the interactions between the logistic processes most faithfully possible, and on the other hand to propose an approach of evaluation of the performance. We called this "tool" "BPMPE" (business process modeling & performance evaluation). We used several constraints to estimate the robustness of the tool.展开更多
Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament(ACL)reconstruction.Interference screw,as a surgical implant in ACL reconstruction,may influence natural loading transmis...Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament(ACL)reconstruction.Interference screw,as a surgical implant in ACL reconstruction,may influence natural loading transmission and contribute to tunnel enlargement.The aims of this study are(1)to quantify the alteration of strain energy density(SED)distribution after the anatomic single-bundle ACL reconstruction;and(2)to characterize the influence of screw length and diameter on the degree of the SED alteration.A validated finite element model of human knee joint was used.The screw length ranging from 20 to 30 mm with screw diameter ranging from 7 to 9 mm were investigated.In the post-operative knee,the SED increased steeply at the extra-articular tunnel aperture under compressive and complex loadings,whereas the SED decreased beneath the screw shaft and nearby the intra-articular tunnel aperture.Increasing the screw length could lower the SED deprivation in the proximal part of the bone tunnel;whereas increasing either screw length or diameter could aggravate the SED deprivation in the distal part of the bone tunnel.Decreasing the elastic modulus of the screw could lower the bone SED deprivation around the screw.In consideration of both graft stability and SED alteration,a biodegradable interference screw with a long length is recommended,which could provide a beneficial mechanical environment at the distal part of the tunnel,and meanwhile decrease the bone-graft motion and synovial fluid propagation at the proximal part of the tunnel.These findings together with the clinical and histological factors could help to improve surgical outcome,and serve as a preliminary knowledge for the following study of biodegradable interference screw.展开更多
It is important to eliminate lipopolysaccharide(LPS)along with killing bacteria in periprosthetic joint infection(PJI)therapy for promoting bone repair due to its effect to regulate macrophages response.Although natur...It is important to eliminate lipopolysaccharide(LPS)along with killing bacteria in periprosthetic joint infection(PJI)therapy for promoting bone repair due to its effect to regulate macrophages response.Although natural antimicrobial peptides(AMPs)offer a good solution,the unknown toxicity,high cost and exogenetic immune response hamper their applications in clinic.In this work,we fabricated a nanowire-like composite material,named P@C,by combining chitosan and puerarin via solid-phase reaction,which can finely mimic the bio-functions of AMPs.Chitosan,serving as the bacteria membrane puncture agent,and puerarin,serving as the LPS target agent,synergistically destroy the bacterial membrane structure and inhibit its recovery,thus endowing P@C with good antibacterial property.In addition,P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation modulation.The in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat.P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property,and its ability of LPS elimination and immunomodulation.P@C can well mimic the functions of AMPs,which provides a novel and effective method for treating the PJI in clinic.展开更多
With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterial...With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.展开更多
The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technolog...The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.展开更多
Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women.Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selecti...Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women.Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators(SERMs)has been associated with various clinical drawbacks.We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein,called HKUOT-S2 protein(32 kDa),from Dioscorea opposita Thunb that can accelerate bone defect healing.Here,we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors(ERs)ERα,ERβ,and GPR30 expressions in vivo.Also,HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers,ALP,and RUNX2 expressions,ALP activity,and osteoblast biomineralization in vitro.Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions,osteoblasts differentiation,and functions.Finally,we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties.Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis.Currently,there is no or limited data if any,on osteoanabolic SERMs.The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.展开更多
Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft substitutes.Never...Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft substitutes.Nevertheless,the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies.Hence,the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important.To address this problem,addition of various growth factors,such as bone morphogenetic proteins(BMPs),parathyroid hormone(PTH)and platelet rich plasma(PRP),into structural allografts and synthetic substitutes have been considered.Although clinical applications of these factors have exhibited good bone formation,their further application was limited due to high cost and potential adverse side effects.Alternatively,bioinorganic ions such as magnesium,strontium and zinc are considered as alternative of osteogenic biological factors.Hence,this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.展开更多
In osteoporosis scenario, tissue response to implants is greatly impaired by the deteriorated boneregeneration microenvironment. In the present study, a Mg-containing akermanite (Ak) ceramic wasemployed for the treatm...In osteoporosis scenario, tissue response to implants is greatly impaired by the deteriorated boneregeneration microenvironment. In the present study, a Mg-containing akermanite (Ak) ceramic wasemployed for the treatment of osteoporotic bone defect, based on the hypothesis that both beneficialions (e.g. Mg^2+ ect.) released by the implants and the weak alkaline microenvironment pH (μe-pH) itcreated may play distinct roles in recovering the abnormal bone regeneration by stimulating osteoblasticanabolic effects. The performance of Ak, b-tricalcium phosphate (β-TCP) and Hardystone (Har) in healinga 3 mm bone defect on the ovariectomized (OVX) osteoporotic rat model was evaluated. Our resultsindicated that, there's more new bone formed in Ak group than in β-TCP or Har group at week 9. Theinitial me-pHs of Ak were significantly higher than that of the β-TCP and Blank group, and this weakalkaline condition was maintained till at least 9 weeks post-surgery. Increased osteoblastic activity whichwas indicated by higher osteoid secretion was observed in Ak group at week 4 to week 9. An intermediatelayer which was rich in phosphorus minerals and bound directly to the new forming bone wasdeveloped on the surface of Ak. In a summary, our study demonstrates that Ak exhibits a superior boneregenerative performance under osteoporosis condition, and might be a promising candidate for thetreatment of osteoporotic bone defect and fracture.展开更多
The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical,biological,or physical cues within a local tissue microenvironment.Deeper understanding of how mamma...The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical,biological,or physical cues within a local tissue microenvironment.Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering.This study aims to investigate that the regulation of magnesium cationic(Mg^2+)tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification.It was discovered that moderate Mg^2+content niche(~4.11 mM)led to superior bone regeneration,while Mg^2+-free and strong Mg^2+content(~16.44 mM)discouraged cell adhesion,proliferation and osteogenic differentiation,thereby bone formation was rarely found.When magnesium ions diffused into free Mg zone from concentrated zone in late time point,new bone formation on free Mg zone became significant through intramembranous ossification.This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration.The knowledge of how a Mg^2+cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissuerepairing biomaterials.展开更多
The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from t...The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.展开更多
Promoting metallic magnesium(Mg)-based implants to treat bone diseases in clinics,such as osteosarcoma and bacterial infection,remains a challenging topic.Herein,an iron hydroxide-based composite coating with a twosta...Promoting metallic magnesium(Mg)-based implants to treat bone diseases in clinics,such as osteosarcoma and bacterial infection,remains a challenging topic.Herein,an iron hydroxide-based composite coating with a twostage nanosheet-like structure was fabricated on Mg alloy,and this was followed by a thermal reduction treatment to break some of the surface Fe–OH bonds.The coating demonstrated three positive changes in properties due to the defects.First,the removal of–OH made the coating superhydrophobic,and it had self-cleaning and antifouling properties.This is beneficial for keeping the implants clean and for anti-corrosion before implantation into the human body.Furthermore,the superhydrophobicity could be removed by immersing the implant in a 75%ethanol solution,to further facilitate biological action during service.Second,the color of the coating changed from yellow to brown-black,leading to an increase in the light absorption,which resulted in an excellent photothermal effect.Third,the defects increased the Fe2+content in the coating and highly improved peroxidase activity.Thus,the defect coating exhibited synergistic photothermal/chemodynamic therapeutic effects for bacteria and tumors.Moreover,the coating substantially enhanced the anti-corrosion and biocompatibility of the Mg alloys.Therefore,this study offers a novel multi-functional Mg-based implant for osteosarcoma therapy.展开更多
Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2...Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.展开更多
The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by t...The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),National Key Research and Development Plan(2018YFC1105103).展开更多
The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by th...The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).展开更多
The design of orthopedic biomaterials has gradually shifted from“immune-friendly”to“immunomodulatory,”in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local...The design of orthopedic biomaterials has gradually shifted from“immune-friendly”to“immunomodulatory,”in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration.Despite the well-known effects of bioactive metallic ions on osteogenesis,how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied.Herein,we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation(Mg^(2+))in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid(PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions.The results suggest that the Mg^(2+)-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory(IL-10)and pro-osteogenic(BMP-2 and TGF-β1)cytokines production.It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.The in vivo results further verify that a large amount of bony tissue,with comparable bone mineral density and mechanical properties,has been generated at an early post-surgical stage in rat intramedullary bone defect models.This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.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
Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery.Stem cells have been found to have osteogenic capabilities.It is necessary to study the influences ...Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery.Stem cells have been found to have osteogenic capabilities.It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo.In this paper,we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings,including surface chemistry,surface roughness and microporosity.In addition,mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals.In the final part,the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.展开更多
Surface mechanical attrition treatment(SMAT)method is an effective way to generate nanograined(NG)surface on Ti-25 Nb-3 Mo-2 Sn-3 Zr(wt.%)(named as TLM),a kind ofβ-type titanium alloy,and the achieved nanocrystalline...Surface mechanical attrition treatment(SMAT)method is an effective way to generate nanograined(NG)surface on Ti-25 Nb-3 Mo-2 Sn-3 Zr(wt.%)(named as TLM),a kind ofβ-type titanium alloy,and the achieved nanocrystalline surface was proved to promote positive functions of osteoblastic cells.In this work,to further endow the NG TLM alloy with both good osteogenic and antibacterial properties,magnesium(Mg),silver(Ag)ion or both were introduced onto the NG TLM surface by ion implantation process,as a comparison,the Mg and Ag ions were also co-implanted onto coarsegrained(CG)TLM surface.The obtained results show that subsequent ion implantation does not remarkably induce the surface roughness and topography alteration of the SMAT-treated layers,and it also has little impact on the microstructure of the SMAT-derivedβ-Ti nanograins.In addition,the implanted Mg and Ag ions are observed to exist as MgO and metallic Ag na noparticles(NPs)embedding tightly in theβ-Ti matrix with grain size of about 15 and 7 nm,respectively.Initial cell adhesion and functions(including proliferation,osteo-differentiation and extracellular matrix mineralization)of rabbit bone marrow mesenchymal stem cells(rBMMSCs)and the bacterial colonization of Staphylococcus aureus(S.aureus)on the different surfaces were investigated.The in-vitro experimental results reveal that the Mg and Ag single-ion implanted NG surface either significantly promotes the rBMMSCs response or inhibits the growth ofS.aureus,whereas the Mg/Ag coimplanted NG surface could concurrently enhance the rBMMSCs functions as well as inhibit the bacterial growth compared to the NG surface,and this efficacy is more pronounced as compared to the Mg/Ag co-implantation in the CG surface.The SMAT-achieved nanograins in the TLM surface layer are identified to not only play a leading role in determining the fate of rBMMSCs but also facilitate fabricating dualfunctio nal surface with both good osteogenic and antibacterial activities through co-implantation of Mg and Ag ions.Our investigation provides a new strategy to develop high-performance Ti-based implants for clinical application.展开更多
Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization proc...Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure.Hence,improving osseointegration and transplantation efficiency remains important.The alteration of bone tissue microenvironment(TME)to facilitate osseointegration has been generally recognized.However,the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging.To address this concern,an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment.The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique.The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated.In the animal test,superior osseointegration between Mg-enriched graft and host bone was found,whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation.Furthermore,the bony in-growth appeared on magnesium-enriched allograft bone was significant higher.The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells.Lastly,our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.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
文摘In this paper, we develop a hybrid model based on SCOR and BPMN to model the operational processes of a platform of cross docking. The interest of the developed model is its dynamic capacity to describe the interactions between the logistic processes most faithfully possible, and on the other hand to propose an approach of evaluation of the performance. We called this "tool" "BPMPE" (business process modeling & performance evaluation). We used several constraints to estimate the robustness of the tool.
基金supported by the National Science & Technology Pillar Program of China(2012BAI18B07 and 2012BAI22B02)the National Natural Science Foundation of China(10925208 and 11120101001)the National Key Lab of Virtual Reality Technology
文摘Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament(ACL)reconstruction.Interference screw,as a surgical implant in ACL reconstruction,may influence natural loading transmission and contribute to tunnel enlargement.The aims of this study are(1)to quantify the alteration of strain energy density(SED)distribution after the anatomic single-bundle ACL reconstruction;and(2)to characterize the influence of screw length and diameter on the degree of the SED alteration.A validated finite element model of human knee joint was used.The screw length ranging from 20 to 30 mm with screw diameter ranging from 7 to 9 mm were investigated.In the post-operative knee,the SED increased steeply at the extra-articular tunnel aperture under compressive and complex loadings,whereas the SED decreased beneath the screw shaft and nearby the intra-articular tunnel aperture.Increasing the screw length could lower the SED deprivation in the proximal part of the bone tunnel;whereas increasing either screw length or diameter could aggravate the SED deprivation in the distal part of the bone tunnel.Decreasing the elastic modulus of the screw could lower the bone SED deprivation around the screw.In consideration of both graft stability and SED alteration,a biodegradable interference screw with a long length is recommended,which could provide a beneficial mechanical environment at the distal part of the tunnel,and meanwhile decrease the bone-graft motion and synovial fluid propagation at the proximal part of the tunnel.These findings together with the clinical and histological factors could help to improve surgical outcome,and serve as a preliminary knowledge for the following study of biodegradable interference screw.
基金National Natural Science Foundation of China(U21A20100,32000938)Science and Technology Commission of Shanghai Municipality,China(19JC1415500,20ZR1465000)+1 种基金Shenzhen Science and Technology Funding(JCYJ20210324120009026)S&T Innovation 2025 Major Special Program of Ningbo(2018B10040)are acknowledged.
文摘It is important to eliminate lipopolysaccharide(LPS)along with killing bacteria in periprosthetic joint infection(PJI)therapy for promoting bone repair due to its effect to regulate macrophages response.Although natural antimicrobial peptides(AMPs)offer a good solution,the unknown toxicity,high cost and exogenetic immune response hamper their applications in clinic.In this work,we fabricated a nanowire-like composite material,named P@C,by combining chitosan and puerarin via solid-phase reaction,which can finely mimic the bio-functions of AMPs.Chitosan,serving as the bacteria membrane puncture agent,and puerarin,serving as the LPS target agent,synergistically destroy the bacterial membrane structure and inhibit its recovery,thus endowing P@C with good antibacterial property.In addition,P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation modulation.The in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat.P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property,and its ability of LPS elimination and immunomodulation.P@C can well mimic the functions of AMPs,which provides a novel and effective method for treating the PJI in clinic.
基金supported by National Natural Science Foundation of China(82071167,82001095,81970975,81901055,82201124,82201119)China Postdoctoral Science Foundation(2021TQ0379,2022M713575)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515110380,2023A1515011963)Health and Medical Research Fund(No.09201466)the Food and Health Bureau,the Government of the HKSAR,China.
文摘With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.
基金The authors would like to thank Li LI and H.Z.Xie for the technical support.This work was financially supported by the National Natural Science Foundation of China(Nos.82002303 and 81702171)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022A1515011536,2021A1515220093,2021A1515220086,2019A1515111156,and 2022A1515011815)+7 种基金the Scientific Research Foundation of Peking University Shenzhen hospital(No.KYQD2021064)the Health and Medical Research Fund(No.19180712)the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(No.201806081018272960)the Shenzhen Science and Technology Innovation Committee Projects(Nos.JCYJ20190809182213535 and JSGG20180507183242702)the program from Shanghai Municipal Health Commission(No.201740165)the National Key R&D Program of China(No.2018YFC1105100)the Hong Kong Innovation Technology Fund(Nos.ITS/287/17 and ITS/405/18)the Hong Kong Research Grant Council General Research Fund(No.17214516).
文摘The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.
基金supported by the Seed Fund for Translational and Applied Research from the University Research Committee(URC),The University of Hong Kong(HKU),Hong Kong China(Project Codes:201910160024 and 202010160009).
文摘Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women.Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators(SERMs)has been associated with various clinical drawbacks.We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein,called HKUOT-S2 protein(32 kDa),from Dioscorea opposita Thunb that can accelerate bone defect healing.Here,we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors(ERs)ERα,ERβ,and GPR30 expressions in vivo.Also,HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers,ALP,and RUNX2 expressions,ALP activity,and osteoblast biomineralization in vitro.Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions,osteoblasts differentiation,and functions.Finally,we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties.Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis.Currently,there is no or limited data if any,on osteoanabolic SERMs.The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.
基金This work was supported in part by Shenzhen Science and Technology Innovation Funding JCYJ20140414090541811,JCYJ20160429190821781 and JCYJ2016429185449249Hong Kong Research Grant Council General Research Funds(RGC GRF)(Nos.718913E,17214516,N_HKU725/16)+3 种基金HKU Seeding Fund(Nos.201511160001 and 201411159045)Hong Kong Innovation Technology Fund(No.ITS/147/15)Hong Kong Health and Medical Research Fund(No.03142446)National Natural Science Foundation of China(NSFC)(Nos.31370957).
文摘Bone grafts have been predominated used to treat bone defects,delayed union or non-union,and spinal fusion in orthopaedic clinically for a period of time,despite the emergency of synthetic bone graft substitutes.Nevertheless,the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies.Hence,the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important.To address this problem,addition of various growth factors,such as bone morphogenetic proteins(BMPs),parathyroid hormone(PTH)and platelet rich plasma(PRP),into structural allografts and synthetic substitutes have been considered.Although clinical applications of these factors have exhibited good bone formation,their further application was limited due to high cost and potential adverse side effects.Alternatively,bioinorganic ions such as magnesium,strontium and zinc are considered as alternative of osteogenic biological factors.Hence,this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.
基金This work was supported by grants from the National Natural Science Foundation of China(No.51272274,81672227,51372170)Shenzhen Peacock Program(No.110811003586331)Shenzhen Science and Technology Research funding(No.CXZZ 20150401152251209,JSGG20151030140325149,JSGG20150331154931068,CXZZ20140417113430716)and partially from Hong Kong General Research Fund.
文摘In osteoporosis scenario, tissue response to implants is greatly impaired by the deteriorated boneregeneration microenvironment. In the present study, a Mg-containing akermanite (Ak) ceramic wasemployed for the treatment of osteoporotic bone defect, based on the hypothesis that both beneficialions (e.g. Mg^2+ ect.) released by the implants and the weak alkaline microenvironment pH (μe-pH) itcreated may play distinct roles in recovering the abnormal bone regeneration by stimulating osteoblasticanabolic effects. The performance of Ak, b-tricalcium phosphate (β-TCP) and Hardystone (Har) in healinga 3 mm bone defect on the ovariectomized (OVX) osteoporotic rat model was evaluated. Our resultsindicated that, there's more new bone formed in Ak group than in β-TCP or Har group at week 9. Theinitial me-pHs of Ak were significantly higher than that of the β-TCP and Blank group, and this weakalkaline condition was maintained till at least 9 weeks post-surgery. Increased osteoblastic activity whichwas indicated by higher osteoid secretion was observed in Ak group at week 4 to week 9. An intermediatelayer which was rich in phosphorus minerals and bound directly to the new forming bone wasdeveloped on the surface of Ak. In a summary, our study demonstrates that Ak exhibits a superior boneregenerative performance under osteoporosis condition, and might be a promising candidate for thetreatment of osteoporotic bone defect and fracture.
基金This work was financially supported by the National key R&D Program of China(2018YFC1105100)Health and Medical Research Fund(19180712)+5 种基金Shenzhen Science and Technology Funds(JSGG20180507183242702)Hong Kong Innovation Technology Fund(ITS/287/17 and ITS/405/18)Hong Kong Research Grant Council General Research Fund(17214516)the Science and Technology Commission of Shanghai Municipality(18410760600)International Partnership Program of Chinese Academy of Sciences(GJHZ1850)National Natural Science Foundation of China(81572113).
文摘The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical,biological,or physical cues within a local tissue microenvironment.Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering.This study aims to investigate that the regulation of magnesium cationic(Mg^2+)tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification.It was discovered that moderate Mg^2+content niche(~4.11 mM)led to superior bone regeneration,while Mg^2+-free and strong Mg^2+content(~16.44 mM)discouraged cell adhesion,proliferation and osteogenic differentiation,thereby bone formation was rarely found.When magnesium ions diffused into free Mg zone from concentrated zone in late time point,new bone formation on free Mg zone became significant through intramembranous ossification.This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration.The knowledge of how a Mg^2+cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissuerepairing biomaterials.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)+3 种基金Science Technology Project of Guangzhou City(2019ZD15)Collegiate Innovation and Entrepreneurship Education Project of Guangzhou City(2019PT104)Science and Technology Innovation Project of Foshan City(1920001000025)and National Young Thousand-Talent Scheme to Zhang Zhi-Yong.
文摘The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.
基金the National Key R&D Program of China(2021YFC2400500)Shanghai Committee of Science and Technology,China(20S31901200)+1 种基金GDPH Supporting Fund for Talent Program(KY0120220137 and KY012021462)Postdoctoral Science Foundation of China(2022M723288).
文摘Promoting metallic magnesium(Mg)-based implants to treat bone diseases in clinics,such as osteosarcoma and bacterial infection,remains a challenging topic.Herein,an iron hydroxide-based composite coating with a twostage nanosheet-like structure was fabricated on Mg alloy,and this was followed by a thermal reduction treatment to break some of the surface Fe–OH bonds.The coating demonstrated three positive changes in properties due to the defects.First,the removal of–OH made the coating superhydrophobic,and it had self-cleaning and antifouling properties.This is beneficial for keeping the implants clean and for anti-corrosion before implantation into the human body.Furthermore,the superhydrophobicity could be removed by immersing the implant in a 75%ethanol solution,to further facilitate biological action during service.Second,the color of the coating changed from yellow to brown-black,leading to an increase in the light absorption,which resulted in an excellent photothermal effect.Third,the defects increased the Fe2+content in the coating and highly improved peroxidase activity.Thus,the defect coating exhibited synergistic photothermal/chemodynamic therapeutic effects for bacteria and tumors.Moreover,the coating substantially enhanced the anti-corrosion and biocompatibility of the Mg alloys.Therefore,this study offers a novel multi-functional Mg-based implant for osteosarcoma therapy.
基金All animal experimental procedures were carried out strictly according to the protocol approved by the University of Hong Kong(HKU)Ethics Committee,Committee on the Use of Live Animals in Teaching and Research(CULATR),(CULATR 5502-20).
文摘Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.
文摘The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),National Key Research and Development Plan(2018YFC1105103).
文摘The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).
基金supported by the National key R&D Program of China(2018YFC1105100)Guangdong Basic and Applied Basic Research Foundation(2019A1515111156)+8 种基金China Postdoctoral Science Foundation(2019M653060)NSFC/RGC Joint Research Scheme(No.N_HKU725/16)Health and Medical Research Fund(19180712)Shenzhen Science and Technology Funds(JSGG20180507183242702)Hong Kong Innovation Technology Fund(ITS/287/17 and ITS/405/18)Hong Kong Research Grant Council General Research Fund(No.17214516)the Science and Technology Commission of Shanghai Municipality(No.18410760600)International Partnership Program of Chinese Academy of Sciences(GJHZ1850)National Natural Science Foundation of China(81572113).
文摘The design of orthopedic biomaterials has gradually shifted from“immune-friendly”to“immunomodulatory,”in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration.Despite the well-known effects of bioactive metallic ions on osteogenesis,how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied.Herein,we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation(Mg^(2+))in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid(PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions.The results suggest that the Mg^(2+)-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory(IL-10)and pro-osteogenic(BMP-2 and TGF-β1)cytokines production.It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.The in vivo results further verify that a large amount of bony tissue,with comparable bone mineral density and mechanical properties,has been generated at an early post-surgical stage in rat intramedullary bone defect models.This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.
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This work is jointly supported by Special Prophase Program for Key Basic Research of the Ministry of Science and Technology of China(973 Program)No.2014CB660809the National Natural Science Foundation of China,Nos.51422102,and 81271715Hubei Provincial Natural Science Foundation Nos.2013CFA018 and 2014CFB551.
文摘Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery.Stem cells have been found to have osteogenic capabilities.It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo.In this paper,we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings,including surface chemistry,surface roughness and microporosity.In addition,mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals.In the final part,the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.
基金financially supported by the National Natural Science Foundation of China(Nos.81501598,51631007 and 31700860)the China Postdoctoral Science Foundation(No.2017M612052)+1 种基金the Postdoctoral Foundation of Anhui Province(No.2017B211)the General Research Fund of Research Grant Council of Hong Kong(Nos.N HKU725-16,17207719 and 17214516)。
文摘Surface mechanical attrition treatment(SMAT)method is an effective way to generate nanograined(NG)surface on Ti-25 Nb-3 Mo-2 Sn-3 Zr(wt.%)(named as TLM),a kind ofβ-type titanium alloy,and the achieved nanocrystalline surface was proved to promote positive functions of osteoblastic cells.In this work,to further endow the NG TLM alloy with both good osteogenic and antibacterial properties,magnesium(Mg),silver(Ag)ion or both were introduced onto the NG TLM surface by ion implantation process,as a comparison,the Mg and Ag ions were also co-implanted onto coarsegrained(CG)TLM surface.The obtained results show that subsequent ion implantation does not remarkably induce the surface roughness and topography alteration of the SMAT-treated layers,and it also has little impact on the microstructure of the SMAT-derivedβ-Ti nanograins.In addition,the implanted Mg and Ag ions are observed to exist as MgO and metallic Ag na noparticles(NPs)embedding tightly in theβ-Ti matrix with grain size of about 15 and 7 nm,respectively.Initial cell adhesion and functions(including proliferation,osteo-differentiation and extracellular matrix mineralization)of rabbit bone marrow mesenchymal stem cells(rBMMSCs)and the bacterial colonization of Staphylococcus aureus(S.aureus)on the different surfaces were investigated.The in-vitro experimental results reveal that the Mg and Ag single-ion implanted NG surface either significantly promotes the rBMMSCs response or inhibits the growth ofS.aureus,whereas the Mg/Ag coimplanted NG surface could concurrently enhance the rBMMSCs functions as well as inhibit the bacterial growth compared to the NG surface,and this efficacy is more pronounced as compared to the Mg/Ag co-implantation in the CG surface.The SMAT-achieved nanograins in the TLM surface layer are identified to not only play a leading role in determining the fate of rBMMSCs but also facilitate fabricating dualfunctio nal surface with both good osteogenic and antibacterial activities through co-implantation of Mg and Ag ions.Our investigation provides a new strategy to develop high-performance Ti-based implants for clinical application.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)+6 种基金National Key Research and Development Plan(2018YFC1105103)Research Grant Council General Research Funds(RGC GRF)(17214516)Shenzhen Science and Technology Innovation Funding(JCYJ20160429190821781 and JCYJ2016429185449249)Science Technology Project of Guangzhou City(201804010185)Science and Technology Innovation Project of Foshan City(1920001000025)Scientific Research Foundation of PEKING UNIVERSITY SHENZHEN HOSPITAL KYQD(2021064)National Young Thousand-Talent Scheme to Zhang Zhi-Yong.
文摘Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure.Hence,improving osseointegration and transplantation efficiency remains important.The alteration of bone tissue microenvironment(TME)to facilitate osseointegration has been generally recognized.However,the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging.To address this concern,an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment.The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique.The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated.In the animal test,superior osseointegration between Mg-enriched graft and host bone was found,whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation.Furthermore,the bony in-growth appeared on magnesium-enriched allograft bone was significant higher.The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells.Lastly,our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.
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”.