pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microsc...pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.展开更多
The poor survival of mesenchymal stem cells （MSCs） compromises the efficacy of stem cell therapy. Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell the...The poor survival of mesenchymal stem cells （MSCs） compromises the efficacy of stem cell therapy. Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy. In this study, the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms. Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining. Signaling pathways involved in serumdeprivation induced apoptosis were analyzed using Western blotting. The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment. Serum deprivation was shown to lead to protein expression alterations in Bax, Bcl-2, casepase-3, casepase-8, GRP78, and CHOP during experiments. The data suggested that the mitochondria death pathway, the extrinsic apoptotic pathway and the endoplastic reticulum（ER） stress pathway were all involved in MSCs apoptosis. The increase in expression of CHOP and the simultaneous decrease in Bcl- 2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.展开更多
Reading guide 1778Repair of long-segment peripheral nerve defects1779Bionic reconstruction of hand function after adult brachial plexus root avulsion1780Optimized design of regeneration material for the treatment of p...Reading guide 1778Repair of long-segment peripheral nerve defects1779Bionic reconstruction of hand function after adult brachial plexus root avulsion1780Optimized design of regeneration material for the treatment of peripheral nerve injury1781Synergism of electroactive polymeric materials and electrical stimulation promotes peripheral nerve repair1783Schwann cell effect on peripheral nerve repair and regeneration .展开更多
This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined...This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined the nanodrug’s therapeutic efficacy.An integral analytical method was used to characterize the structure of MPEG-PCL.The single factor method and orthogonal test were utilized to investigate the optimum preparation process.The morphology and average size of the OMT-NPs were analyzed by transmission electron microscopy and Zetasizer.CCK-8 assay and confocal fluorescent microscope were used to study the inhibitory effect on SGC-7901 gastric cancer cells.The average size of nanoparticles was 95.86±1.54 nm.The maximum encapsulation efficiency of OMT was 46.84±4.37%,while the drug loading content was 8.89±1.09%.The cumulative release of nanoparticles was 73.07±1.5%,inspected through dynamic dialysis in vitro.Compared with free OMT,OMT-NPs showed enhanced cytotoxic effects in SGC-7901 cells.The nanoparticles could efficiently deliver the OMT into the cancer cells and release it.The OMT delivery system prepared in this paper provides a potential platform for the treatment of gastric cancer..展开更多
We synthesized photo-responsive carboxymethyl chitosan(CMC-MA)via free radical polymerization and utilized nanoclay laponite(LAP)as an inorganic crosslinking agent to develop an injectable and 3D-printable CMC-MA/LAP ...We synthesized photo-responsive carboxymethyl chitosan(CMC-MA)via free radical polymerization and utilized nanoclay laponite(LAP)as an inorganic crosslinking agent to develop an injectable and 3D-printable CMC-MA/LAP hydrogel.We determined the optimal ratio of 2.5 w/v%CMC-MA/7.5 w/v%LAP based on injection molding,compression modulus,swelling properties,rheological properties,and 3D printing properties of the hydrogel system.In-vitro cytocompatibility experiments showed that both CMC-MA and CMC-MA/LAP hydrogel had no inhibitory effect on cell proliferation and can promote cell growth when cultured on the surface of the hydrogel matrix.Moreover,the hydrogel containing LAP particles significantly facilitated cell adhesion(>60%)compared with the hydrogel without LAP(20%).Our findings demonstrate that the CMC-MA/LAP hydrogel has great potential for tissue repair in neural tissue engineering.展开更多
The use of a nerve conduit provides an opportunity to regulate cytokines,growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects.We constructed a poly-D-L-lactide(PDLLA)-based ner...The use of a nerve conduit provides an opportunity to regulate cytokines,growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects.We constructed a poly-D-L-lactide(PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]}andβ-tricalcium phosphate.The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats.We observed the nerve morphology in the early period of regeneration,35 days post injury,using hematoxylin-eosin and methylene blue staining.Compared with the PDLLA conduit,the nerve fibers in the PDLLA-based bioactive nerve conduit were thicker and more regular in size.Muscle fibers in the soleus muscle had greater diameters in the PDLLA bioactive group than in the PDLLA only group.The PDLLA-based bioactive nerve conduit is a promising strategy for repair after sciatic nerve injury.展开更多
The 60Fc and 70Fc SF/SA blend scaffolds were prepared to mimic the functions of the native ECM for skin regeneration.Human Umbilical Vein Endothelial Cells(HUVECs)were used to examine the cell cytotoxicity,adhesion,gr...The 60Fc and 70Fc SF/SA blend scaffolds were prepared to mimic the functions of the native ECM for skin regeneration.Human Umbilical Vein Endothelial Cells(HUVECs)were used to examine the cell cytotoxicity,adhesion,growth factors secretion and the gene expression of associated angiogenic factors.Cell proliferation,adhesion and live-dead analyses showed that HUVECs could better attach,grow,and proliferate on the 70Fc scaffolds compared with 60Fc scaffolds and unmodified controls.Furthermore,the 70Fc scaffolds showed higher levels of specific angiogenic proteins and genes expression as well.This study suggests that the involvement of higher composition of SF(about 70%)than that of SA on the blended scaffolds could be advantageous as it is more suitable to promote angiogenesis,which is potential for vascularization during skin repair.展开更多
We prepared graphene（GE） with a mean size of 3087 nm.The transition of graphene oxide（GO） to GE was confirmed by UV-visible spectroscopy,Fourier transform infrared spectroscopy（FTIR） and X-ray diffraction（XRD）...We prepared graphene（GE） with a mean size of 3087 nm.The transition of graphene oxide（GO） to GE was confirmed by UV-visible spectroscopy,Fourier transform infrared spectroscopy（FTIR） and X-ray diffraction（XRD）.The experimental results of optical microscopic observation indicated that the GE ranged from 5 to 20 μg/mL did not affect the cell morphologies of the PC12 cells.The results of cell viability and membrane integrity assay supported that of optical microscopic observation and demonstrated that the GE ranged from 5 to 20 μg/mL presented no obvious cytotoxicity.However,reactive oxygen species（ROS） assay suggested that an elevation of ROS level could be detected when the GE ranged from 20 to 100 μg/mL.These results showed that the GE ranged from 5 to 10 μg/mL presented an excellent in vitro biocompatibility and was one kind of potential biomaterials for neural tissue engineering.展开更多
The authors regret that the supplementary Fig.S12 is incorrect.This correction does not affect any of the results and conclusions in the text.Fig.S11 and S12 are studies on hydration kinetics and hydration products of...The authors regret that the supplementary Fig.S12 is incorrect.This correction does not affect any of the results and conclusions in the text.Fig.S11 and S12 are studies on hydration kinetics and hydration products of M/P=2 and M/P=4 respectively.In the previous uploaded version,the caption and figures of the Fig.S12 are the same as Fig.S11.We have corrected the error and the correct figures are as follows.The authors are sorry for not checking the supplementary documents carefully before publication.展开更多
In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system be...In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system because of the spatial complexity of osteochondral units in composition,structure and functions.In order to repair the hierarchical tissue involving different layers of articular cartilage,cartilage-bone interface and subchondral bone,traditional clinical treatments including palliative and reparative methods have showed certain improvement in pain relief and defect filling.It is the development of tissue engineering that has provided more promising results in regenerating neo-tissues with comparable compositional,structural and functional characteristics to the native osteochondral tissues.Here in this review,some basic knowledge of the osteochondral units including the anatomical structure and composition,the defect classification and clinical treatments will be first introduced.Then we will highlight the recent progress in osteochondral tissue engineering from perspectives of scaffold design,cell encapsulation and signaling factor incorporation including bioreactor application.Clinical products for osteochondral defect repair will be analyzed and summarized later.Moreover,we will discuss the current obstacles and future directions to regenerate the damaged osteochondral tissues.展开更多
A kind of degradable magnesium phosphate bone cement(MPBC)was fabricated by using the mixed powders of magnesium oxide(MgO),potassium dihydrogen phosphate(KH_(2)PO_(4))and calcium dihydrogen phosphate(Ca(H_(2)PO_(4))2...A kind of degradable magnesium phosphate bone cement(MPBC)was fabricated by using the mixed powders of magnesium oxide(MgO),potassium dihydrogen phosphate(KH_(2)PO_(4))and calcium dihydrogen phosphate(Ca(H_(2)PO_(4))2.H_(2)O).As MgKPO_(4),the main product of MgO and KH_(2)PO_(4)was alkaline,the Ca(H_(2)PO_(4))2.H_(2)Owas added to neutralize the alkali of the system.And the effects of Ca(H_(2)PO_(4))2.H_(2)Oon the performance of MPBC were discussed.The results showed that the adding of Ca(H_(2)PO_(4))2.H_(2)Oextended the setting time,which was about 6 min to 18 min.The compressive strength increased first and then decreased,and maximum value reached 31.2MPa after setting for 24 h without any additional pressure.The MPBC was degradable in Tris–HCl solution,and the extracts of the cytotoxicity assay showed that the MPBC had good biocompatibility,indicating that the MPBC had good biodegradable and biocompatible properties.展开更多
Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectabi...Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.展开更多
In this paper, polyurethane （PU） materials with different contents of hard segment （20%, 25%, 30%） were prepared based on hexamethylene diisocyanate and polycarbonate diols by solution polymerization. The obtained...In this paper, polyurethane （PU） materials with different contents of hard segment （20%, 25%, 30%） were prepared based on hexamethylene diisocyanate and polycarbonate diols by solution polymerization. The obtained polycarbonate-urethane （PCU） elastomers were characterized by very good hydrophobic property and excellent resistance to hydrolysis. Hemolysis, recalification time and platelet-rich plasma adhesion were used to evaluate the blood compatibility of the materials. L929 cells cultured with leach liquor of these PU membranes were selected to perform the cytotoxicity experiments. The results indicate that the hemolysis rates of PU membranes are all less than 5%, which can meet the requirement of the national standards for biomaterials. However, compared with 20% and 30% groups, the recalification time of the sample containing 25% hard segment is longer, while the number of platelet adhesion is less. Additionally, cells cultured in the leach liquor of PU membranes with 25% hard segment proliferated relatively more thriving, meaning that this proportion of the material has the lowest cytotoxicity.展开更多
As a superior alternative to sutures,tissue adhesives have been developed significantly in recent years.However,existing tissue adhesives struggle to form fast and stable adhesion between tissue interfaces,bond weakly...As a superior alternative to sutures,tissue adhesives have been developed significantly in recent years.However,existing tissue adhesives struggle to form fast and stable adhesion between tissue interfaces,bond weakly in wet environments and lack bioactivity.In this study,a degradable and bioactive citrate-based polyurethane adhesive is constructed to achieve rapid and strong tissue adhesion.The hydrophobic layer was created with polycaprolactone to overcome the bonding failure between tissue and adhesion layer in wet environments,which can effectively improve the wet bonding strength.This citrate-based polyurethane adhesive provides rapid,non-invasive,liquid-tight and seamless closure of skin incisions,overcoming the limitations of sutures and commercial tissue adhesives.In addition,it exhibits biocompatibility,biodegradability and hemostatic properties.The degradation product citrate could promote the process of angiogenesis and accelerate wound healing.This study provides a novel approach to the development of a fast-adhering wet tissue adhesive and provides a valuable contribution to the development of polyurethane-based tissue adhesives.展开更多
Metal-based nanomaterials usually have broad-spectrum antibacterial properties,low biological toxicity and no drug resistance due to their intrinsic enzyme-like catalytic properties and external field(magnetic,thermal...Metal-based nanomaterials usually have broad-spectrum antibacterial properties,low biological toxicity and no drug resistance due to their intrinsic enzyme-like catalytic properties and external field(magnetic,thermal,acoustic,optical and electrical)responsiveness.Herein,iron oxide(Fe_(3)O_(4))nanoparticles(IONPs)synthesized by us have good biosafety,excellent photothermal conversion ability and peroxidase-like catalytic activity,which can be used to construct a photothermal-enzymes combined antibacterial treatment platform.IONPs with peroxide-like catalytic activity can induce H_(2)O_(2)to catalyze the production of·OH in a slightly acidic environment,thus achieving certain bactericidal effects and increasing the sensitivity of bacteria to heat.When stimulated by near-infrared light,the photothermal effect could destroy bacterial cell membranes,resulting in cleavage and inactivation of bacterial protein,DNA or RNA.Meanwhile,it can also improve the catalytic activity of peroxidase-like and promote IONPs to catalyze the production of more·OH for killing bacteria.After IONPs synergistic treatment,the antibacterial rate of Escherichia coli and Staphylococcus aureus reached nearly 100%.It also has an obvious killing effect on bacteria in infected wounds of mice and can effectively promote the healing of S.aureusinfected wounds,which has great application potential in clinical anti-infection treatment.展开更多
There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,i...There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.展开更多
Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,a...Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,and are non-absorbable,or hard to cure under wet conditions.Herein,inspired by the cement-based adhesive used in the industry field,we report a bioactive calcium and magnesium phosphate bone adhesive(MPBA)with the properties of facile preparation,robust adhesion,and bioactive.MPBA is equipped with similar strength to cancellous bones and shows reliable bonding performance for various interfaces,such as Ti6Al4V,Al2O3,and poly(ether-ether-ketone).MPBA achieves excellent bonding ability for the above interfaces with the bonding strengths of 2.28±0.47,2.32±0.15,and 1.44±0.38 MPa,respectively.Besides,it also shows reliable fixation ability for bovine bone surfaces.The bonding behavior to materials and bones suggests that MPBA could be used for both fracture treatment and implant fixation.Meanwhile,MPBA possesses good biological activity,which could promote the vascularization process and osteogenic differentiation.Finally,in vivo experiments confirmed MPBA can effectively restore bone strength and promote bone regeneration.展开更多
Diabetic wounds are a difficult medical challenge.Excessive secretion of matrix metalloproteinase-9(MMP-9)in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular dama...Diabetic wounds are a difficult medical challenge.Excessive secretion of matrix metalloproteinase-9(MMP-9)in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage,which seriously hinders diabetic wound healing.To solve these issues,a double-network porous hydrogel composed of poly(methyl methacrylate-co-acrylamide)(p(MMA-co-AM))and polyvinyl alcohol(PVA)was constructed by the high internal phase emulsion(HIPE)technique for the delivery of potassium sucrose octasulfate(PSO),a drug that can inhibit MMPs,increase angiogenesis and improve microcirculation.The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies,high porosity,high specific surface area,excellent mechanical properties and suitable swelling properties.Meanwhile,the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release.In addition,both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds,increasing growth factor secretion,improving vascularization,increasing collagen deposition and promoting re-epithelialization.Therefore,this study provided a reliable therapeutic strategy for diabetic wound healing,some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity,high drug-loading performance and excellent mechanical properties.展开更多
Bone defect repair remains a troubling problem in clinical orthopedics,which involves complex biological processes.Calcium phosphates(CaPs)have been widely used owing to their advantage of biocompatibility.However,sin...Bone defect repair remains a troubling problem in clinical orthopedics,which involves complex biological processes.Calcium phosphates(CaPs)have been widely used owing to their advantage of biocompatibility.However,single component and traditional fabrication methods cannot meet the requirements of bioadaptability during the tissue repair process.In this work,0%,5%,15%,25%wt%of BG-TCP(bioactive glass-β-tricalcium phosphate)bioresorbable scaffolds with triply-periodic minimal surfaces(TPMS)-gyroid structure were prepared by the stereolithography(SLA)technology.TPMS-gyroid structure provided an accurate mimicry of natural bone tissue,and the incorporation of BG improved the compressive strength ofβ-TCP matrix,matched with the defective bone(2–12 MPa).Rapid but tunable degradation kinetics(compared with pure TCP)of BG enabled the BG-TCP system to sh8ow adaptable biodegradability to new bone generation.In vitro studies have shown that composite scaffolds have better mechanical properties(7.82 MPa),and can released appropriate contents of calcium,phosphorous,and magnesium ions,which promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and angiogenic ability of endothelial progenitor cells(EPCs).Moreover,the in vivo assessment of rat femoral defect revealed that TPMS-structure-based TCP scaffolds accelerated bone ingrowth to the pores.Moreover,BG-TCP scaffolds,especially 15BG-TCP group,exhibited superior bone regeneration capacity at both 4 and 8 weeks,which achieved an optimal match between the rate of material degradation and tissue regeneration.In summary,this study provides insight into influences of bioactive components(BG)and bionic structures(TPMS)on the physical-chemical properties of materials,cell behavior and tissue regeneration,which offers a promising strategy to design bioadaptive ceramic scaffolds in the clinical treatment of bone defects.展开更多
基金Funded by the National Key R&D Program of China(No.2023YFC2412300)the Natural Science Foundation of Hubei Province(No.2022CFB386)the National Natural Science Foundation of China(No.52073222)。
文摘pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.
基金This study was supported by grants from the National Natural Science Foundation of China （No. NSC31300791） and the Opening Project of Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients （No. HLPAI 2014006）.
文摘The poor survival of mesenchymal stem cells （MSCs） compromises the efficacy of stem cell therapy. Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy. In this study, the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms. Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining. Signaling pathways involved in serumdeprivation induced apoptosis were analyzed using Western blotting. The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment. Serum deprivation was shown to lead to protein expression alterations in Bax, Bcl-2, casepase-3, casepase-8, GRP78, and CHOP during experiments. The data suggested that the mitochondria death pathway, the extrinsic apoptotic pathway and the endoplastic reticulum（ER） stress pathway were all involved in MSCs apoptosis. The increase in expression of CHOP and the simultaneous decrease in Bcl- 2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.
基金supported by the National Natural Science Foundation of ChinaNo.31271055+37 种基金3147094420906088funded by the Chinese National Ministry of Science and Technology 973 ProjectNo.2014CB542201863 ProjectNo.SS2015AA020501the Ministry of Education Innovation Team(IRT1201)the National Natural Science FundNo.31571235313712103127128431171150the Educational Ministry New Century Excellent Talents Support ProjectNo.BMU20110270supported by the National Natural Science Foundation of ChinaNo.31200799 and 81571198the New Century Excellent Talents in UniversityNo.NCET-12-0742the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Key Talent Fund Project of "Science Education for Health"Engineering of Health Department of Jiangsu Province of ChinaNo.RC2011101funded by Chinese National Ministry of Science and Technology 973 ProjectNo.2014CB542202Natural Science Foundation of ChinaNo.8137135481571182Natural Science Foundation of Guangdong ProvinceNo.S2013010014697Science and Technology Foundation of Guangdong ProvinceNo.2015A020212024funded by the National Natural Science Foundation of ChinaNo.3117094631300805the People’s Liberation Army 12th Five-Year Plan PeriodNo.BWS11J025the National Basic Research Program of ChinaNo.2012CB5181062014CB542201
文摘Reading guide 1778Repair of long-segment peripheral nerve defects1779Bionic reconstruction of hand function after adult brachial plexus root avulsion1780Optimized design of regeneration material for the treatment of peripheral nerve injury1781Synergism of electroactive polymeric materials and electrical stimulation promotes peripheral nerve repair1783Schwann cell effect on peripheral nerve repair and regeneration .
基金Funded by the National Natural Science Foundation of China(No.51273156)the Health Commission of Hubei Province Scientific Research Project(No.WJ2019H275)。
文摘This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined the nanodrug’s therapeutic efficacy.An integral analytical method was used to characterize the structure of MPEG-PCL.The single factor method and orthogonal test were utilized to investigate the optimum preparation process.The morphology and average size of the OMT-NPs were analyzed by transmission electron microscopy and Zetasizer.CCK-8 assay and confocal fluorescent microscope were used to study the inhibitory effect on SGC-7901 gastric cancer cells.The average size of nanoparticles was 95.86±1.54 nm.The maximum encapsulation efficiency of OMT was 46.84±4.37%,while the drug loading content was 8.89±1.09%.The cumulative release of nanoparticles was 73.07±1.5%,inspected through dynamic dialysis in vitro.Compared with free OMT,OMT-NPs showed enhanced cytotoxic effects in SGC-7901 cells.The nanoparticles could efficiently deliver the OMT into the cancer cells and release it.The OMT delivery system prepared in this paper provides a potential platform for the treatment of gastric cancer..
基金Funded by the Natural Science Foundation of Hubei Province(No.2022CFB386)。
文摘We synthesized photo-responsive carboxymethyl chitosan(CMC-MA)via free radical polymerization and utilized nanoclay laponite(LAP)as an inorganic crosslinking agent to develop an injectable and 3D-printable CMC-MA/LAP hydrogel.We determined the optimal ratio of 2.5 w/v%CMC-MA/7.5 w/v%LAP based on injection molding,compression modulus,swelling properties,rheological properties,and 3D printing properties of the hydrogel system.In-vitro cytocompatibility experiments showed that both CMC-MA and CMC-MA/LAP hydrogel had no inhibitory effect on cell proliferation and can promote cell growth when cultured on the surface of the hydrogel matrix.Moreover,the hydrogel containing LAP particles significantly facilitated cell adhesion(>60%)compared with the hydrogel without LAP(20%).Our findings demonstrate that the CMC-MA/LAP hydrogel has great potential for tissue repair in neural tissue engineering.
基金supported by a grant from the National Key Basic Research Program of China,No.2011CB606205a grant from the National Natural Science Foundation of China,No.51403168+1 种基金a grant from the Major Scientific and Technological Research Projects of the Ministry of Education of China,No.313041a grant from the Scientific and Technological Cooperation Projects of Hong Kong,Macao and Taiwan,China,No.2015DFH30180
文摘The use of a nerve conduit provides an opportunity to regulate cytokines,growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects.We constructed a poly-D-L-lactide(PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]}andβ-tricalcium phosphate.The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats.We observed the nerve morphology in the early period of regeneration,35 days post injury,using hematoxylin-eosin and methylene blue staining.Compared with the PDLLA conduit,the nerve fibers in the PDLLA-based bioactive nerve conduit were thicker and more regular in size.Muscle fibers in the soleus muscle had greater diameters in the PDLLA bioactive group than in the PDLLA only group.The PDLLA-based bioactive nerve conduit is a promising strategy for repair after sciatic nerve injury.
基金Supported by the Major Special projects of technological innovation of Hubei Province,China(No.2017ACA168)the National Key R&D Program of China(No.2017YFC1103800)。
文摘The 60Fc and 70Fc SF/SA blend scaffolds were prepared to mimic the functions of the native ECM for skin regeneration.Human Umbilical Vein Endothelial Cells(HUVECs)were used to examine the cell cytotoxicity,adhesion,growth factors secretion and the gene expression of associated angiogenic factors.Cell proliferation,adhesion and live-dead analyses showed that HUVECs could better attach,grow,and proliferate on the 70Fc scaffolds compared with 60Fc scaffolds and unmodified controls.Furthermore,the 70Fc scaffolds showed higher levels of specific angiogenic proteins and genes expression as well.This study suggests that the involvement of higher composition of SF(about 70%)than that of SA on the blended scaffolds could be advantageous as it is more suitable to promote angiogenesis,which is potential for vascularization during skin repair.
基金Funded by the Natural Science Foundation of Hubei Province(No.2014CFB839)the Doctoral Research Fund of Wuhan University of Technology(No.471-40120093)+4 种基金the Opening Project of Jiangsu Provincial Key Laboratory of Silk Engineering(No.KJS1415)the Hong Kong,Macao and Taiwan Science&Technology Cooperation Program of China(No.2015DFH30180)the Fundamental Research Funds for the Central Universities(No.WUT:2014-Ⅶ-028)the National Natural Science Foundation of China(No.51403168)the Key Project of Science and Technology of Wuhan(No.2014060202010120)
文摘We prepared graphene（GE） with a mean size of 3087 nm.The transition of graphene oxide（GO） to GE was confirmed by UV-visible spectroscopy,Fourier transform infrared spectroscopy（FTIR） and X-ray diffraction（XRD）.The experimental results of optical microscopic observation indicated that the GE ranged from 5 to 20 μg/mL did not affect the cell morphologies of the PC12 cells.The results of cell viability and membrane integrity assay supported that of optical microscopic observation and demonstrated that the GE ranged from 5 to 20 μg/mL presented no obvious cytotoxicity.However,reactive oxygen species（ROS） assay suggested that an elevation of ROS level could be detected when the GE ranged from 20 to 100 μg/mL.These results showed that the GE ranged from 5 to 10 μg/mL presented an excellent in vitro biocompatibility and was one kind of potential biomaterials for neural tissue engineering.
文摘The authors regret that the supplementary Fig.S12 is incorrect.This correction does not affect any of the results and conclusions in the text.Fig.S11 and S12 are studies on hydration kinetics and hydration products of M/P=2 and M/P=4 respectively.In the previous uploaded version,the caption and figures of the Fig.S12 are the same as Fig.S11.We have corrected the error and the correct figures are as follows.The authors are sorry for not checking the supplementary documents carefully before publication.
基金This work was supported by grants from the National Natural Science Foundation of China(No.51772233)the National Key Research and Development Program of China(2018YFB1105500)+3 种基金the Major Special Projects of Technological Innovation of Hubei Province(No.2019ACA130)the Application Foundation and Front Research Program of Wuhan(No.2018010401011273)Foshan Xianhu Laboratory of the Advanced Energy Science and Technology Guangdong Laboratory(XHT2020-008)the Fundamental Research Funds for the Central Universities(2020-YB-015).
文摘In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system because of the spatial complexity of osteochondral units in composition,structure and functions.In order to repair the hierarchical tissue involving different layers of articular cartilage,cartilage-bone interface and subchondral bone,traditional clinical treatments including palliative and reparative methods have showed certain improvement in pain relief and defect filling.It is the development of tissue engineering that has provided more promising results in regenerating neo-tissues with comparable compositional,structural and functional characteristics to the native osteochondral tissues.Here in this review,some basic knowledge of the osteochondral units including the anatomical structure and composition,the defect classification and clinical treatments will be first introduced.Then we will highlight the recent progress in osteochondral tissue engineering from perspectives of scaffold design,cell encapsulation and signaling factor incorporation including bioreactor application.Clinical products for osteochondral defect repair will be analyzed and summarized later.Moreover,we will discuss the current obstacles and future directions to regenerate the damaged osteochondral tissues.
基金This work was supported by Major Program of National Natural Science Foundation of China(811901330)the Natural Science Foundation of Hubei Province(2015CFB551)and Science and Technology Project of Wuhan(2015060101010032).
文摘A kind of degradable magnesium phosphate bone cement(MPBC)was fabricated by using the mixed powders of magnesium oxide(MgO),potassium dihydrogen phosphate(KH_(2)PO_(4))and calcium dihydrogen phosphate(Ca(H_(2)PO_(4))2.H_(2)O).As MgKPO_(4),the main product of MgO and KH_(2)PO_(4)was alkaline,the Ca(H_(2)PO_(4))2.H_(2)Owas added to neutralize the alkali of the system.And the effects of Ca(H_(2)PO_(4))2.H_(2)Oon the performance of MPBC were discussed.The results showed that the adding of Ca(H_(2)PO_(4))2.H_(2)Oextended the setting time,which was about 6 min to 18 min.The compressive strength increased first and then decreased,and maximum value reached 31.2MPa after setting for 24 h without any additional pressure.The MPBC was degradable in Tris–HCl solution,and the extracts of the cytotoxicity assay showed that the MPBC had good biocompatibility,indicating that the MPBC had good biodegradable and biocompatible properties.
基金supported by grants from The National Key Research and Development Program of China(2022YFB4601402)the National Natural Science Foundation of China(32201109,51772233,51861145306)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515120052,2021A1515110557)the Self-innovation Research Funding Project of Hanjiang Laboratory(HJL202202A002).
文摘Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.
文摘In this paper, polyurethane （PU） materials with different contents of hard segment （20%, 25%, 30%） were prepared based on hexamethylene diisocyanate and polycarbonate diols by solution polymerization. The obtained polycarbonate-urethane （PCU） elastomers were characterized by very good hydrophobic property and excellent resistance to hydrolysis. Hemolysis, recalification time and platelet-rich plasma adhesion were used to evaluate the blood compatibility of the materials. L929 cells cultured with leach liquor of these PU membranes were selected to perform the cytotoxicity experiments. The results indicate that the hemolysis rates of PU membranes are all less than 5%, which can meet the requirement of the national standards for biomaterials. However, compared with 20% and 30% groups, the recalification time of the sample containing 25% hard segment is longer, while the number of platelet adhesion is less. Additionally, cells cultured in the leach liquor of PU membranes with 25% hard segment proliferated relatively more thriving, meaning that this proportion of the material has the lowest cytotoxicity.
基金supported by grants from the National Natural Science Foundation of China(52372272,32201109,32360234)the Key Basic Research Program of Shenzhen(JCYJ20200109150218836)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515120052,2021A1515110557)the Self-innovation Research Funding Project of Hanjiang Laboratory(HJL202202A002).
文摘As a superior alternative to sutures,tissue adhesives have been developed significantly in recent years.However,existing tissue adhesives struggle to form fast and stable adhesion between tissue interfaces,bond weakly in wet environments and lack bioactivity.In this study,a degradable and bioactive citrate-based polyurethane adhesive is constructed to achieve rapid and strong tissue adhesion.The hydrophobic layer was created with polycaprolactone to overcome the bonding failure between tissue and adhesion layer in wet environments,which can effectively improve the wet bonding strength.This citrate-based polyurethane adhesive provides rapid,non-invasive,liquid-tight and seamless closure of skin incisions,overcoming the limitations of sutures and commercial tissue adhesives.In addition,it exhibits biocompatibility,biodegradability and hemostatic properties.The degradation product citrate could promote the process of angiogenesis and accelerate wound healing.This study provides a novel approach to the development of a fast-adhering wet tissue adhesive and provides a valuable contribution to the development of polyurethane-based tissue adhesives.
基金supported by grants from the National Natural Science Foundation of China(51772233,51861145306)the Major Special Project of Technological Innovation of Hubei Province(2019ACA130)+2 种基金the Key Basic Research Program of Shenzhen(JCYJ20200109150218836)Foshan Xianhu Laboratory of the Advanced Energy Science and Technology Guangdong Laboratory(XHT2020-008)the Fundamental Research Funds for the Central Universities(2020-YB-015).
文摘Metal-based nanomaterials usually have broad-spectrum antibacterial properties,low biological toxicity and no drug resistance due to their intrinsic enzyme-like catalytic properties and external field(magnetic,thermal,acoustic,optical and electrical)responsiveness.Herein,iron oxide(Fe_(3)O_(4))nanoparticles(IONPs)synthesized by us have good biosafety,excellent photothermal conversion ability and peroxidase-like catalytic activity,which can be used to construct a photothermal-enzymes combined antibacterial treatment platform.IONPs with peroxide-like catalytic activity can induce H_(2)O_(2)to catalyze the production of·OH in a slightly acidic environment,thus achieving certain bactericidal effects and increasing the sensitivity of bacteria to heat.When stimulated by near-infrared light,the photothermal effect could destroy bacterial cell membranes,resulting in cleavage and inactivation of bacterial protein,DNA or RNA.Meanwhile,it can also improve the catalytic activity of peroxidase-like and promote IONPs to catalyze the production of more·OH for killing bacteria.After IONPs synergistic treatment,the antibacterial rate of Escherichia coli and Staphylococcus aureus reached nearly 100%.It also has an obvious killing effect on bacteria in infected wounds of mice and can effectively promote the healing of S.aureusinfected wounds,which has great application potential in clinical anti-infection treatment.
基金support of the National Natural Science Foundation of China(No.81802689,51772233)the Provincial Key Research and Development Program of Hubei,China(No.2020BCB058)+2 种基金State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(2021-KF-22)the Major Special Projects of Technological Innovation of Hubei Province(No.2019ACA130)the Application Foundation and Front Research Program of Wuhan(No.2018010401011273).
文摘There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.
基金supported by grants from the National Key Research and Development Program of China(No.2022YFB4601402)the National Natural Science Foundation of China(Nos.32201109,51772233,and 51861145306)+2 种基金the Key Basic Research Program of Shenzhen(No.JCYJ20200109150218836)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120052 and 2021A1515110557)the Laboratory Self-innovation Research Funding Project of Hanjiang Laboratory(No.HJL202202A002).
文摘Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,and are non-absorbable,or hard to cure under wet conditions.Herein,inspired by the cement-based adhesive used in the industry field,we report a bioactive calcium and magnesium phosphate bone adhesive(MPBA)with the properties of facile preparation,robust adhesion,and bioactive.MPBA is equipped with similar strength to cancellous bones and shows reliable bonding performance for various interfaces,such as Ti6Al4V,Al2O3,and poly(ether-ether-ketone).MPBA achieves excellent bonding ability for the above interfaces with the bonding strengths of 2.28±0.47,2.32±0.15,and 1.44±0.38 MPa,respectively.Besides,it also shows reliable fixation ability for bovine bone surfaces.The bonding behavior to materials and bones suggests that MPBA could be used for both fracture treatment and implant fixation.Meanwhile,MPBA possesses good biological activity,which could promote the vascularization process and osteogenic differentiation.Finally,in vivo experiments confirmed MPBA can effectively restore bone strength and promote bone regeneration.
基金supported by the National Key Research and Development Program of China(2022YFB4601402)the National Natural Science Foundation of China(32201109,51772233,82072446)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515120052,2021A1515110557)the Key Basic Research Program of Shenzhen(JCYJ20200109150218836)the Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory(HJL202202A002)the Trauma Microsurgery Clinical Medical Research Center of Hubei Province and the Health Commission of Hubei Province Medical Leading Talent Project(LJ20200405).
文摘Diabetic wounds are a difficult medical challenge.Excessive secretion of matrix metalloproteinase-9(MMP-9)in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage,which seriously hinders diabetic wound healing.To solve these issues,a double-network porous hydrogel composed of poly(methyl methacrylate-co-acrylamide)(p(MMA-co-AM))and polyvinyl alcohol(PVA)was constructed by the high internal phase emulsion(HIPE)technique for the delivery of potassium sucrose octasulfate(PSO),a drug that can inhibit MMPs,increase angiogenesis and improve microcirculation.The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies,high porosity,high specific surface area,excellent mechanical properties and suitable swelling properties.Meanwhile,the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release.In addition,both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds,increasing growth factor secretion,improving vascularization,increasing collagen deposition and promoting re-epithelialization.Therefore,this study provided a reliable therapeutic strategy for diabetic wound healing,some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity,high drug-loading performance and excellent mechanical properties.
基金financially supported by the National Key Research and Development Program of China(Nos.2022YFB4601402)the National Natural Science Foundation of China(Nos.32201109,51772233)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120052,2021A1515110557)the Key Basic Research Program of Shenzhen(No.JCYJ20200109150218836)the Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory(No.HJL202202A002)。
文摘Bone defect repair remains a troubling problem in clinical orthopedics,which involves complex biological processes.Calcium phosphates(CaPs)have been widely used owing to their advantage of biocompatibility.However,single component and traditional fabrication methods cannot meet the requirements of bioadaptability during the tissue repair process.In this work,0%,5%,15%,25%wt%of BG-TCP(bioactive glass-β-tricalcium phosphate)bioresorbable scaffolds with triply-periodic minimal surfaces(TPMS)-gyroid structure were prepared by the stereolithography(SLA)technology.TPMS-gyroid structure provided an accurate mimicry of natural bone tissue,and the incorporation of BG improved the compressive strength ofβ-TCP matrix,matched with the defective bone(2–12 MPa).Rapid but tunable degradation kinetics(compared with pure TCP)of BG enabled the BG-TCP system to sh8ow adaptable biodegradability to new bone generation.In vitro studies have shown that composite scaffolds have better mechanical properties(7.82 MPa),and can released appropriate contents of calcium,phosphorous,and magnesium ions,which promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and angiogenic ability of endothelial progenitor cells(EPCs).Moreover,the in vivo assessment of rat femoral defect revealed that TPMS-structure-based TCP scaffolds accelerated bone ingrowth to the pores.Moreover,BG-TCP scaffolds,especially 15BG-TCP group,exhibited superior bone regeneration capacity at both 4 and 8 weeks,which achieved an optimal match between the rate of material degradation and tissue regeneration.In summary,this study provides insight into influences of bioactive components(BG)and bionic structures(TPMS)on the physical-chemical properties of materials,cell behavior and tissue regeneration,which offers a promising strategy to design bioadaptive ceramic scaffolds in the clinical treatment of bone defects.
