Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural bones.However,the rapid degradation of magnesium alloys in biological media hinders successful implantation.Refinem...Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural bones.However,the rapid degradation of magnesium alloys in biological media hinders successful implantation.Refinement of microstructure,as well as reinforcement particles can significantly improve the degradation rate.In this work,multi-pass friction stir processing(FSP)was proposed to synthesize WE43/nano-hydroxyapatite(n HA)surface composite,the microstructure,reinforced particle distribution,micro-hardness,corrosion behavior and in-vitro bioactivity were studied.The subsequent FSP passes of WE43 alloy and WE43/n HA composite refined the grain size which was reduced by 94.29%and 95.92%(2.63 and 1.88μm,respectively)compared to base metal after three passes.This resulted in increasing the microhardness by 120%(90.86 HV0.1)and 135%(105.59 HV0.1)for the WE43 and WE43-n HA,respectively.It is found that increasing FSP passes improved the uniform distribution of n HA particles within the composite matrix which led to improved corrosion resistance and less degradation rate.The corrosion rate of the FSPed WE43/n HA composite after three passes was reduced by 38.2%(4.13 mm/year)and the degradation rate was reduced by 69.7%(2.87 mm/y).This is attributed to secondary phase(Mg24Y5and Mg41Nd5)particle fragmentation and redistribution,as well as a homogeneous distribution of n HA.Additionally,the growing Ca-P and Mg(OH)2layer formed on the surface represented a protective layer that reduced the degradation rate.The wettability test revealed a relatively hydrophilic surface with water contact angle of 49.1±2.2°compared to 71.2±2.1°for base metal.Also,biomineralization test showed that apatite layer grew after immersion 7d in simulated body fluid with atomic ratio of Ca/P 1.60 approaching the stoichiometric ratio(1.67)indicating superior bioactivity of FSPed WE43/n HA composite after three passes.These results raise that the grain refinement by FSP and introduction of n HA particles significantly improved the degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications.展开更多
Nano-hydroxyapatite/poly( ε-caprolactone)( n HA/PCL)composite materials are among the best candidates for application in bone tissue engineering. As the main technique to fabricate porous scaffolds, electrospinning p...Nano-hydroxyapatite/poly( ε-caprolactone)( n HA/PCL)composite materials are among the best candidates for application in bone tissue engineering. As the main technique to fabricate porous scaffolds, electrospinning produce scaffolds with unsatisfactory mechanical strength and limited pore size for cell infiltration.Micron-sized fiber assembly with higher mechanical strength is qualified to structure hybrid scaffolds. In this study, n HA/PCL monofilament fibers with different mass ratios were fabricated through melt-spinning. Transmission electron microscope( TEM)was used to observe the aggregation between n HA particles. Other characterizations including scanning electron microscopy( SEM),attenuated total reflection Fourier transform infrared spectroscopy( ATR-FTIR) and X-ray diffraction( XRD) were done to discuss the morphology, components and crystallization of the n HA/PCL composite fibers, respectively. The influence of n HA/PCL mass ratio on the tensile properties and water contact angle of composite fibers was also studied. The SEM images show the homogeneous dispersion of nano particles in the polymer matrix. Besides,n HA content increases the tensile strength, initial modulus and hydrophilicity of the composite fibers under the premise of spinnability. This kind of fibers is strong enough to fabricate fiber assembly which may have potential application in bone tissue engineering.展开更多
Vascular calcification(VC)is a common characteristic of aging,diabetes,chronic renal failure,and atherosclerosis.The basic component of VC is hydroxyapatite(HAp).Nano-sized HAp(nHAp)has been identified to play an esse...Vascular calcification(VC)is a common characteristic of aging,diabetes,chronic renal failure,and atherosclerosis.The basic component of VC is hydroxyapatite(HAp).Nano-sized HAp(nHAp)has been identified to play an essential role in the development of pathological calcification of vasculature.However,whether nHAp can induce calcification in vivo and the mechanism of nHAp in the progression of VC remains unclear.We discovered that nHAp existed both in vascular smooth muscle cells(VSMCs)and their extracellular matrix(ECM)in the calcified arteries from patients.Synthetic nHAp had similar morphological and chemical properties as natural nHAp recovered from calcified artery.nHAp stimulated osteogenic differentiation and accelerated mineralization of VSMCs in vitro.Synthetic nHAp could also directly induce VC in vivo.Mechanistically,nHAp was internalized into lysosome,which impaired lysosome vacuolar H+-ATPase for its acidification,therefore blocked autophagic flux in VSMCs.Lysosomal re-acidification by cyclic-3′,5′-adenosine monophosphate(cAMP)significantly enhanced autophagic degradation and attenuated nHAp-induced calcification.The accumulated autophagosomes and autolysosomes were converted into calcium-containing exosomes which were secreted into ECM and accelerated vascular calcium deposit.Inhibition of exosome release in VSMCs decreased calcium deposition.Altogether,our results demonstrated a repressive effect of nHAp on lysosomal acidification,which inhibited autophagic degradation and promoted a conversion of the accumulated autophagic vacuoles into exosomes that were loaded with undissolved nHAp,Ca^(2+),Pi and ALP.These exosomes bud off the plasma membrane,deposit within ECM,and form calcium nodules.Vascular calcification was thus accelerated by nHAP through blockage of autophagic flux in VSMCs.展开更多
The use of various types of calcium phosphate has been reported in the preparation of repairing materials for bone defects.However,the physicochemical and biological properties among them might be vastly different.In ...The use of various types of calcium phosphate has been reported in the preparation of repairing materials for bone defects.However,the physicochemical and biological properties among them might be vastly different.In this study,we prepared two types of calcium phosphates,nano-hydroxyapatite(nHA)and natural bone ceramic(NBC),into 3D scaffolds by mixing with type I collagen(CoL),resulting in the nHA/CoL and NBC/CoL scaffolds.We then evaluated and compared the physicochemical and biological properties of these two calcium phosphates and their composite scaffold with CoL.Scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),Fourier-transform infrared spectroscopy(FTIR),X-ray diffraction spectroscopy(XRD)and compressive tests were used to,respectively,characterize the morphology,composition,distribution and the effect of nHA and NBC to collagen.Next,we examined the biological properties of the scaffolds using cytotoxicity testing,flow cytometry,immunofluorescence staining,biocompatibility testing,CCK-8 assays and RT-PCR.The results reflected that the Ca2t released from nHA and NBC could bind chemically with collagen and affect its physicochemical properties,including the infrared absorption spectrum and compression modulus,among others.Furthermore,the two kinds of scaffolds could promote the expression of osteo-relative genes,but showed different gene induction properties.In short,NBC/CoL could promote the expression of early osteogenic genes,while nHA/CoL could upregulate late osteogenic genes.Conclusively,these two composite scaffolds could provide MC3T3-E1 cells with a biomimetic surface for adhesion,proliferation and the formation of mineralized extracellular matrices.Moreover,nHA/CoL and NBC/CoL had different effects on the period and extent ofMC3T3-E1 cell mineralization.展开更多
Damage of axon and glial scars formation both inhibit nerve regenerative growth during nerve injury.In addition,mechanical stretch at high displacement rates of 10%tensile strain can cause marked nerve injury,it is im...Damage of axon and glial scars formation both inhibit nerve regenerative growth during nerve injury.In addition,mechanical stretch at high displacement rates of 10%tensile strain can cause marked nerve injury,it is important for finding a proper nano biomaterial to repair nerve injury.Nano-hydroxyapatite(n-HA)has excellent biocompatibility and high bioactivity,which is a good candidate for biomedical engineering applications.But the certain mechanism of n-HA on the injured nerve is seldom reported.In this study,we determined the role of n-HA on the mechanical stretch-induced nerve injury at adult rat spine.Mechanical stretch under strain 10%at displacement rates of 60 mm/min can cause marked broken vessels and edema in spinal cord and dorsal root ganglion tissue in haematoxylin-eosin(HE)staining.However,n-HA application can reverse hemorrhage and edema triggered by high rates of 60 mm/min stretch.Moreover,n-HA can promote positive staining of Netrin-1 increase significantly in spinal cord and dorsal root ganglion tested by immunohistochemistry(IHC)staining.In general,our study indicated that n-HA can repair mechanical stretch-induced nerve injury,it may provide a new approach to block injury and accelerate nerve regeneration in future.展开更多
Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP f...Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP from one another. The blood compatibility of nHAP is also determined by blood solubil-ity experiment so that the capability of different dispersant dis-persing against nHAP of different concentration and the relation between nHAP and blood compatibility have been determined. The inhibiting function of Bel-7402 against tumor cells is deter-mined with the MTT staining method. The study result shows that heparin sodium has the best dispersing efficiency for nHAP with-out the phenomenon of hemolysis.展开更多
Biomaterial-associated infection(BAI)is a kind of serious post-operative complication in orthopaedic surgery.Antibiotic-loaded bone cement shines a light on BAI prevention for convenient manipulation and complex filli...Biomaterial-associated infection(BAI)is a kind of serious post-operative complication in orthopaedic surgery.Antibiotic-loaded bone cement shines a light on BAI prevention for convenient manipulation and complex filling.To this aim,we designed an antibacterial bone cement based on Nano-hydroxyapatite/Polyurethane(PUHA)loading with antibiotic Enoxacin(EN).The distinct shear-thinning behavior of the prepolymers was observed,indicating a good injectability.The PUHA bone cement possessed a suitable curing speed,and the addition of EN might slightly expedite the curing process and enhance the mechanical properties.The EN release profile indicated that the EN-loaded bone cement could reach the minimum inhibitory concentration in 2 h,and sustainedly released EN for almost 8 days,exhibiting an antibacterial delivery potential.Antibacterial test further confirmed the antibacterial ability of EN-loaded bone cement is in a dose-dependent manner.However,the osteogenic performance of drug-loaded bone cement with high dosage is not as good as antibacterial activity.When the EN concentration of antibacterial cement was lower than 32μg·mL^(-1),the proliferation and osteogenic differentiation of rat mesenchymal stem cells could be significantly promoted.Overall,this study verified the potential of the EN-loaded PUHA bone cement in anti-infection and osteogenesis for bone repairing.展开更多
Nanotechnology has revolutionized the field of biology and medicine in the 21 st century.Bone injury incidences during sports activities are common,and they are traditionally treated with allogeneic grafting,a common ...Nanotechnology has revolutionized the field of biology and medicine in the 21 st century.Bone injury incidences during sports activities are common,and they are traditionally treated with allogeneic grafting,a common clinical practice but limited by the quality of the graft and some side effects.Nano-hydroxyapatite(nHA)is considered as an ideal bone graft material owing to its bone-like structure,excellent biological activity,bone conductivity,non-toxicity,and non-immunogenicity.nHA and its composite materials have been found suitable for the adhesion,proliferation,and differentiation of mesenchymal stem cells,which leads to their potential applications in treating the bone injury.In this review,we classified different applications of nHA to explore the role of these materials in bone repair and tendon healing,highlighting the superior characteristics of nanomaterials in the treatment of bone injury,hoping to provide ideas for nHA applied to clinical practices for the treatment of bone injury.展开更多
Natural nano-hydroxyapatite(HA)was extracted from Pacific cod(Gadus macrocephalus)bone with a thermostable col-lagenolytic protease in the present study.Conditions for the enzymatic reaction were optimized to be 60℃a...Natural nano-hydroxyapatite(HA)was extracted from Pacific cod(Gadus macrocephalus)bone with a thermostable col-lagenolytic protease in the present study.Conditions for the enzymatic reaction were optimized to be 60℃and pH 7.0,and a desir-able extraction efficiency was achieved by using the crude collagenolytic protease.Dynamic light scattering,transmission electron microscopy and energy-dispersive X-ray analysis revealed that nano-HA are anionic spherical(about 110nm)particles mainly com-prised of calcium and phosphorus at an approximate ratio of 5:3.As evaluated with the mouse ex vivo intestinal segments,the extracted nano-HA displayed comparable level of intestinal bioavailability to the positive control CaCl_(2).By treating with inhibitors(NaN3,ami-loride)and low temperature(4℃),clathrin-mediated endocytosis was assumed to involve the intestinal absorption of nano-HA.Over-all,the application of thermostable collagenolytic protease is proved to be a promising alternative method for nano-HA extraction from natural resource with improved ecological and biological value.展开更多
To evaluate the retention properties of the novel ‘C'-shaped molar bands at a laboratory level. Resin-modified glass ionomer cement(RMGIC) was used as a luting agent for the novel C-shaped molar band. The mechani...To evaluate the retention properties of the novel ‘C'-shaped molar bands at a laboratory level. Resin-modified glass ionomer cement(RMGIC) was used as a luting agent for the novel C-shaped molar band. The mechanical properties of the band were examined and the retention performance was characterized in the mesial, distal and vertical directions. A clinical trial was conducted using a spilt-mouth design on 50 patients. The novel C-shaped molar bands fit most molars without a repeated try-in process.The use of both nanoHA coating and RMGIC enhanced the tensile(8.00 ± 1.8 MPa) and shear strengths(27.17 ± 8.6 MPa) of the molar bands, leading to high retention in vertical, mesial and distal directions( p < 0.001). In clinical trials, the C-shaped molar bands had a failure rate(15%) comparable to that of traditional bands, and 93% of the failed bands demonstrated an adhesive remnant index score of 0, corroborating the observation that no luting agent residue remained on the tooth surface in most cases. The novel C-shaped molar bands appear to be a promising appliance that requires further clinical investigations, and may be used effectively in orthodontics.展开更多
With the pursuit of new cancer therapies and more effective treatment to diseases in the last decades, nanotechnology has been an important ally for healthcare professionals and patients in critical clinical condition...With the pursuit of new cancer therapies and more effective treatment to diseases in the last decades, nanotechnology has been an important ally for healthcare professionals and patients in critical clinical conditions. Nanomaterials offer an alternative way to deliver toxic chemotherapeutic drugs to specific biological tissues, specific cells or specific microbial beings, resulting in avoidance of strong side effects or resilience to effective drugs. Among these materials, stands out the hydroxyapatite nanoparticles, a ceramic class of calcium phosphates that present chemical and structural similarities with the mineral phase of the human skeleton’s bone matrix, resulting in important biological features, such as biocompatibility, osteoconductive, osteoinduction and osteoaffinity, which led to a lot of scientific researches to apply these nanoparticles for bone diseases diagnosis and therapeutics. Due to the hydroxyapatite biological activities and due to the possibility to promote chemical and physical modifications in these nanoparticles, they can interact with biological cells or microorganisms in different ways, resulting in multiple potentialities to be explored such as apoptosis induction to cancerous cells, osteogenesis promotion, cellular proliferation, angiogenesis and tissue recovery, in addition to promote cell adhesion and cell uptake. Furthermore, chemical and physical modifications, such as surface functionalization, dopant inclusions and radiolabeling process, allow scientists to track the particle activities in biological environments. In the last decades of scientific productions, the literature brings together important data on how hydroxyapatite nanoparticles interact with biological tissues and such data are crucial for the development of more effective therapeutic and diagnostic agents. In the present review, we intend to compile scholarly information to explore the biological relations of nanosized hydroxyapatite with the human cellular environment and the feasible modifications that may improve the theragnostic efficacy of these molecules.展开更多
To study the effect of two composition ratios of nano-hydroxyapatite and collagen(NHAC)composites on repairing alveolar bone defect of dogs.Eighteen healthy adult dogs were randomly divided into three groups.Two kinds...To study the effect of two composition ratios of nano-hydroxyapatite and collagen(NHAC)composites on repairing alveolar bone defect of dogs.Eighteen healthy adult dogs were randomly divided into three groups.Two kinds of the NHAC composites were prepared according to the constituent ratios of 3:7 and 5:5;immediately after extraction of the mandibular second premolars,each kind of the NHAC composite was implanted into extraction socket,respectively:Group I,nHA/Col紏3:7;Group II,nHA/Col紏5:5 and Group III,blank control group.The bone-repairing ability of the two grafts was separately analyzed by morphometric measurement,X-ray tomography examination and biomechanical analysis at 1st,3rd and 6th month post-surgical,respectively.The NHAC composites were absorbed gradually after implanting into alveolar bone defect and were replaced by new bone.The ratios of new bone formation of Group I was significantly higher than that of Group II after 3 months(P<0.05).The structure and bioactive performance can be improved when the ratio between the collagen and the hydroxyapatite was reasonable,and the repairing ability and effect in extraction sockets are obviously better.展开更多
Development of novel biomaterials for bone regeneration is based on the sufficient bone-bonding ability,bioactivity and biocompatibility.In this study,novel flexible poly(butylene succinate)/polydimethysiloxane-modifi...Development of novel biomaterials for bone regeneration is based on the sufficient bone-bonding ability,bioactivity and biocompatibility.In this study,novel flexible poly(butylene succinate)/polydimethysiloxane-modified bioactive glass/nano-hydroxyapatite(PBSu/PDMS-BG/nHA)hybrid bioceramic with various nHA concentration on the in vitro bone-like hydroxyapatite(HA)formation,biomineralization activity and osteoblast cell biocompatibility were investigated.The rapid precipitation of HA on the hybrid bioceramic surfaces was found after being immersed in simulated body fluid(SBF)for seven days.Results show that the amount of HA deposition increased with the increase of nHA concentration.The optimized PBSu/PDMS-BG/nHA hybrid bioceramic exhibited good flexibility,high biomineralization activity and good osteoblast cell biocompatibility.展开更多
In the field of dura mater repair,it is essential to employ artificial substitutes mimicking the multilayered microar-chitecture and multiple functions of native dura mater for effective neurosurgery.However,existing ...In the field of dura mater repair,it is essential to employ artificial substitutes mimicking the multilayered microar-chitecture and multiple functions of native dura mater for effective neurosurgery.However,existing artificial dura mater substitutes commonly cause complications because of mismatched structural and mechanical properties as well as the lack of antibacterial activity or osteogenic capability.In this study,a triple-layered dura mater substi-tute was fabricated by electrohydrodynamic(EHD)jetting techniques,including electrospinning and melt-based EHD printing processes.Highly aligned polycaprolactone(PCL)nanofibers loaded with gentamicin sulfate(GS)were prepared by electrospinning to form the inner layer,which can mimic the aligned collagen fibers of the native dura mater.Random PCL-GS nanofibers were then deposited by electrospinning to form the middle layer.They were intended to enhance the mechanical properties of the fabricated scaffolds.The outer layer involv-ing PCL microfibers doped with nano-hydroxyapatite(nHA)at various angles was printed by the melting-based EHD method,which can enhance osteogenic capability and promote the fusion between the dura mater substi-tute and the skull.The tensile strength of the triple-layered drug-loaded biomimetic dura mater substitute was 22.42±0.89 MPa,and the elongation at break was 36.43%±2.00%.The addition of GS endowed the substitutes with an anti-infection property without influencing their cytocompatibility.Furthermore,the incorporation of nHA promoted the osteogenic differentiation of MC3T3-E1 cells seeded on the triple-layered scaffolds.This work offers a promising strategy to manufacture multilayered dura mater substitutes with the desired antibacterial and enhanced osteogenic capability performance,possibly providing a novel candidate for dural tissue repair.展开更多
Chitin is a kind of seemly material to match PLLA for a scaffold, which may create an appropriate environment for the regeneration of tissues. In this study, we evaluated hydrophilicity of a new nano-hydroxyapatite/co...Chitin is a kind of seemly material to match PLLA for a scaffold, which may create an appropriate environment for the regeneration of tissues. In this study, we evaluated hydrophilicity of a new nano-hydroxyapatite/collagen/PLLA (nHACP) scaffold optimized by chitin fibres for bone tissue engineering. The results show that with the CF content increase, hydrophilicity of nHACP/CF increases, which reflects from the side that the addition of the chitin fibres can improve the cytocompatibility of the nHACP. Moreover, crosslink does not take significant influences on the material hydrophilicity. The results suggest that nHACP/CF with the crosslink should be a kind of potential appropriate scaffold for tissue engineering.展开更多
基金supported by the University Malaya(Grant code:FRGS/1/2022/TK10/UM/02/6)the National Natural Science Foundation of China(Grant No.51275414,No.51605387)Deanship of Scientific Research at King Khalid University for funding this work through the Large Groups Project under grant number RGP.2/303/44。
文摘Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural bones.However,the rapid degradation of magnesium alloys in biological media hinders successful implantation.Refinement of microstructure,as well as reinforcement particles can significantly improve the degradation rate.In this work,multi-pass friction stir processing(FSP)was proposed to synthesize WE43/nano-hydroxyapatite(n HA)surface composite,the microstructure,reinforced particle distribution,micro-hardness,corrosion behavior and in-vitro bioactivity were studied.The subsequent FSP passes of WE43 alloy and WE43/n HA composite refined the grain size which was reduced by 94.29%and 95.92%(2.63 and 1.88μm,respectively)compared to base metal after three passes.This resulted in increasing the microhardness by 120%(90.86 HV0.1)and 135%(105.59 HV0.1)for the WE43 and WE43-n HA,respectively.It is found that increasing FSP passes improved the uniform distribution of n HA particles within the composite matrix which led to improved corrosion resistance and less degradation rate.The corrosion rate of the FSPed WE43/n HA composite after three passes was reduced by 38.2%(4.13 mm/year)and the degradation rate was reduced by 69.7%(2.87 mm/y).This is attributed to secondary phase(Mg24Y5and Mg41Nd5)particle fragmentation and redistribution,as well as a homogeneous distribution of n HA.Additionally,the growing Ca-P and Mg(OH)2layer formed on the surface represented a protective layer that reduced the degradation rate.The wettability test revealed a relatively hydrophilic surface with water contact angle of 49.1±2.2°compared to 71.2±2.1°for base metal.Also,biomineralization test showed that apatite layer grew after immersion 7d in simulated body fluid with atomic ratio of Ca/P 1.60 approaching the stoichiometric ratio(1.67)indicating superior bioactivity of FSPed WE43/n HA composite after three passes.These results raise that the grain refinement by FSP and introduction of n HA particles significantly improved the degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications.
基金Science and Technology Support Program of Shanghai,China(No.16441903803)National Postdoctoral Foundation,China(No.2016M590299)
文摘Nano-hydroxyapatite/poly( ε-caprolactone)( n HA/PCL)composite materials are among the best candidates for application in bone tissue engineering. As the main technique to fabricate porous scaffolds, electrospinning produce scaffolds with unsatisfactory mechanical strength and limited pore size for cell infiltration.Micron-sized fiber assembly with higher mechanical strength is qualified to structure hybrid scaffolds. In this study, n HA/PCL monofilament fibers with different mass ratios were fabricated through melt-spinning. Transmission electron microscope( TEM)was used to observe the aggregation between n HA particles. Other characterizations including scanning electron microscopy( SEM),attenuated total reflection Fourier transform infrared spectroscopy( ATR-FTIR) and X-ray diffraction( XRD) were done to discuss the morphology, components and crystallization of the n HA/PCL composite fibers, respectively. The influence of n HA/PCL mass ratio on the tensile properties and water contact angle of composite fibers was also studied. The SEM images show the homogeneous dispersion of nano particles in the polymer matrix. Besides,n HA content increases the tensile strength, initial modulus and hydrophilicity of the composite fibers under the premise of spinnability. This kind of fibers is strong enough to fabricate fiber assembly which may have potential application in bone tissue engineering.
基金supported by the National Natural Science Foundation of China Grant(No.81570251 and NO.82070448 to HY).
文摘Vascular calcification(VC)is a common characteristic of aging,diabetes,chronic renal failure,and atherosclerosis.The basic component of VC is hydroxyapatite(HAp).Nano-sized HAp(nHAp)has been identified to play an essential role in the development of pathological calcification of vasculature.However,whether nHAp can induce calcification in vivo and the mechanism of nHAp in the progression of VC remains unclear.We discovered that nHAp existed both in vascular smooth muscle cells(VSMCs)and their extracellular matrix(ECM)in the calcified arteries from patients.Synthetic nHAp had similar morphological and chemical properties as natural nHAp recovered from calcified artery.nHAp stimulated osteogenic differentiation and accelerated mineralization of VSMCs in vitro.Synthetic nHAp could also directly induce VC in vivo.Mechanistically,nHAp was internalized into lysosome,which impaired lysosome vacuolar H+-ATPase for its acidification,therefore blocked autophagic flux in VSMCs.Lysosomal re-acidification by cyclic-3′,5′-adenosine monophosphate(cAMP)significantly enhanced autophagic degradation and attenuated nHAp-induced calcification.The accumulated autophagosomes and autolysosomes were converted into calcium-containing exosomes which were secreted into ECM and accelerated vascular calcium deposit.Inhibition of exosome release in VSMCs decreased calcium deposition.Altogether,our results demonstrated a repressive effect of nHAp on lysosomal acidification,which inhibited autophagic degradation and promoted a conversion of the accumulated autophagic vacuoles into exosomes that were loaded with undissolved nHAp,Ca^(2+),Pi and ALP.These exosomes bud off the plasma membrane,deposit within ECM,and form calcium nodules.Vascular calcification was thus accelerated by nHAP through blockage of autophagic flux in VSMCs.
基金the National Key Research and Development Program of China(2018YFA0108200,2018YFC116400)the International Cooperation Project of Hainan Province(KJHZ2015-30)Sci&Tech Program of Guangzhou of China(201803010086).
文摘The use of various types of calcium phosphate has been reported in the preparation of repairing materials for bone defects.However,the physicochemical and biological properties among them might be vastly different.In this study,we prepared two types of calcium phosphates,nano-hydroxyapatite(nHA)and natural bone ceramic(NBC),into 3D scaffolds by mixing with type I collagen(CoL),resulting in the nHA/CoL and NBC/CoL scaffolds.We then evaluated and compared the physicochemical and biological properties of these two calcium phosphates and their composite scaffold with CoL.Scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),Fourier-transform infrared spectroscopy(FTIR),X-ray diffraction spectroscopy(XRD)and compressive tests were used to,respectively,characterize the morphology,composition,distribution and the effect of nHA and NBC to collagen.Next,we examined the biological properties of the scaffolds using cytotoxicity testing,flow cytometry,immunofluorescence staining,biocompatibility testing,CCK-8 assays and RT-PCR.The results reflected that the Ca2t released from nHA and NBC could bind chemically with collagen and affect its physicochemical properties,including the infrared absorption spectrum and compression modulus,among others.Furthermore,the two kinds of scaffolds could promote the expression of osteo-relative genes,but showed different gene induction properties.In short,NBC/CoL could promote the expression of early osteogenic genes,while nHA/CoL could upregulate late osteogenic genes.Conclusively,these two composite scaffolds could provide MC3T3-E1 cells with a biomimetic surface for adhesion,proliferation and the formation of mineralized extracellular matrices.Moreover,nHA/CoL and NBC/CoL had different effects on the period and extent ofMC3T3-E1 cell mineralization.
基金supported by funds from the National Natural Science Foundation of China(NSFC)Research Grant(31971238,51574246,61871014,11827803,31771019)National Key Research and Development Program(2016YFC1100704,2016YFC1102203)+1 种基金also supported by 111 Project(B13003)International Joint Research Center of Aerospace Biotechnology and Medical Engineering,Ministry of Science and Technology,China.
文摘Damage of axon and glial scars formation both inhibit nerve regenerative growth during nerve injury.In addition,mechanical stretch at high displacement rates of 10%tensile strain can cause marked nerve injury,it is important for finding a proper nano biomaterial to repair nerve injury.Nano-hydroxyapatite(n-HA)has excellent biocompatibility and high bioactivity,which is a good candidate for biomedical engineering applications.But the certain mechanism of n-HA on the injured nerve is seldom reported.In this study,we determined the role of n-HA on the mechanical stretch-induced nerve injury at adult rat spine.Mechanical stretch under strain 10%at displacement rates of 60 mm/min can cause marked broken vessels and edema in spinal cord and dorsal root ganglion tissue in haematoxylin-eosin(HE)staining.However,n-HA application can reverse hemorrhage and edema triggered by high rates of 60 mm/min stretch.Moreover,n-HA can promote positive staining of Netrin-1 increase significantly in spinal cord and dorsal root ganglion tested by immunohistochemistry(IHC)staining.In general,our study indicated that n-HA can repair mechanical stretch-induced nerve injury,it may provide a new approach to block injury and accelerate nerve regeneration in future.
基金Supported by the National Basic Research Program of China(973 Program) (2005CB623905)
文摘Nano-hydroxyapatite (nHAP),dispersed with three kinds of dispersants (heparin sodium,polyacrylic sodium and wa-ter),reacted with red blood cell,Bel-7402 tumor cell,to compare their dispersing efficiency against nHAP from one another. The blood compatibility of nHAP is also determined by blood solubil-ity experiment so that the capability of different dispersant dis-persing against nHAP of different concentration and the relation between nHAP and blood compatibility have been determined. The inhibiting function of Bel-7402 against tumor cells is deter-mined with the MTT staining method. The study result shows that heparin sodium has the best dispersing efficiency for nHAP with-out the phenomenon of hemolysis.
基金funded by the Sichuan International Science and Technology Innovation Cooperation Project[Grant Numbers2021YFH0122]the Fundamental Research Funds for the Central Universities。
文摘Biomaterial-associated infection(BAI)is a kind of serious post-operative complication in orthopaedic surgery.Antibiotic-loaded bone cement shines a light on BAI prevention for convenient manipulation and complex filling.To this aim,we designed an antibacterial bone cement based on Nano-hydroxyapatite/Polyurethane(PUHA)loading with antibiotic Enoxacin(EN).The distinct shear-thinning behavior of the prepolymers was observed,indicating a good injectability.The PUHA bone cement possessed a suitable curing speed,and the addition of EN might slightly expedite the curing process and enhance the mechanical properties.The EN release profile indicated that the EN-loaded bone cement could reach the minimum inhibitory concentration in 2 h,and sustainedly released EN for almost 8 days,exhibiting an antibacterial delivery potential.Antibacterial test further confirmed the antibacterial ability of EN-loaded bone cement is in a dose-dependent manner.However,the osteogenic performance of drug-loaded bone cement with high dosage is not as good as antibacterial activity.When the EN concentration of antibacterial cement was lower than 32μg·mL^(-1),the proliferation and osteogenic differentiation of rat mesenchymal stem cells could be significantly promoted.Overall,this study verified the potential of the EN-loaded PUHA bone cement in anti-infection and osteogenesis for bone repairing.
基金Supported by the National Natural Science Foundation of China(31371750)the Natural Science Foundation of Hubei Province(2012FFC010)
文摘Nanotechnology has revolutionized the field of biology and medicine in the 21 st century.Bone injury incidences during sports activities are common,and they are traditionally treated with allogeneic grafting,a common clinical practice but limited by the quality of the graft and some side effects.Nano-hydroxyapatite(nHA)is considered as an ideal bone graft material owing to its bone-like structure,excellent biological activity,bone conductivity,non-toxicity,and non-immunogenicity.nHA and its composite materials have been found suitable for the adhesion,proliferation,and differentiation of mesenchymal stem cells,which leads to their potential applications in treating the bone injury.In this review,we classified different applications of nHA to explore the role of these materials in bone repair and tendon healing,highlighting the superior characteristics of nanomaterials in the treatment of bone injury,hoping to provide ideas for nHA applied to clinical practices for the treatment of bone injury.
基金supported by the Natural Science Foundation of Shandong Province(No.ZR202102270334)the National Key Research and Development Program of China(No.2020YFD0901004).
文摘Natural nano-hydroxyapatite(HA)was extracted from Pacific cod(Gadus macrocephalus)bone with a thermostable col-lagenolytic protease in the present study.Conditions for the enzymatic reaction were optimized to be 60℃and pH 7.0,and a desir-able extraction efficiency was achieved by using the crude collagenolytic protease.Dynamic light scattering,transmission electron microscopy and energy-dispersive X-ray analysis revealed that nano-HA are anionic spherical(about 110nm)particles mainly com-prised of calcium and phosphorus at an approximate ratio of 5:3.As evaluated with the mouse ex vivo intestinal segments,the extracted nano-HA displayed comparable level of intestinal bioavailability to the positive control CaCl_(2).By treating with inhibitors(NaN3,ami-loride)and low temperature(4℃),clathrin-mediated endocytosis was assumed to involve the intestinal absorption of nano-HA.Over-all,the application of thermostable collagenolytic protease is proved to be a promising alternative method for nano-HA extraction from natural resource with improved ecological and biological value.
基金Funded by Department of Education,National Natural Science Foundation of China(No.81170960)Heilongjiang Province(No.11531204)+1 种基金Department of Health,Heilongjiang Province(No.2006-123)Youth Foundation of the Second Affiliated Hospital of Harbin Medical University(No.QN2006-13)
文摘To evaluate the retention properties of the novel ‘C'-shaped molar bands at a laboratory level. Resin-modified glass ionomer cement(RMGIC) was used as a luting agent for the novel C-shaped molar band. The mechanical properties of the band were examined and the retention performance was characterized in the mesial, distal and vertical directions. A clinical trial was conducted using a spilt-mouth design on 50 patients. The novel C-shaped molar bands fit most molars without a repeated try-in process.The use of both nanoHA coating and RMGIC enhanced the tensile(8.00 ± 1.8 MPa) and shear strengths(27.17 ± 8.6 MPa) of the molar bands, leading to high retention in vertical, mesial and distal directions( p < 0.001). In clinical trials, the C-shaped molar bands had a failure rate(15%) comparable to that of traditional bands, and 93% of the failed bands demonstrated an adhesive remnant index score of 0, corroborating the observation that no luting agent residue remained on the tooth surface in most cases. The novel C-shaped molar bands appear to be a promising appliance that requires further clinical investigations, and may be used effectively in orthodontics.
文摘With the pursuit of new cancer therapies and more effective treatment to diseases in the last decades, nanotechnology has been an important ally for healthcare professionals and patients in critical clinical conditions. Nanomaterials offer an alternative way to deliver toxic chemotherapeutic drugs to specific biological tissues, specific cells or specific microbial beings, resulting in avoidance of strong side effects or resilience to effective drugs. Among these materials, stands out the hydroxyapatite nanoparticles, a ceramic class of calcium phosphates that present chemical and structural similarities with the mineral phase of the human skeleton’s bone matrix, resulting in important biological features, such as biocompatibility, osteoconductive, osteoinduction and osteoaffinity, which led to a lot of scientific researches to apply these nanoparticles for bone diseases diagnosis and therapeutics. Due to the hydroxyapatite biological activities and due to the possibility to promote chemical and physical modifications in these nanoparticles, they can interact with biological cells or microorganisms in different ways, resulting in multiple potentialities to be explored such as apoptosis induction to cancerous cells, osteogenesis promotion, cellular proliferation, angiogenesis and tissue recovery, in addition to promote cell adhesion and cell uptake. Furthermore, chemical and physical modifications, such as surface functionalization, dopant inclusions and radiolabeling process, allow scientists to track the particle activities in biological environments. In the last decades of scientific productions, the literature brings together important data on how hydroxyapatite nanoparticles interact with biological tissues and such data are crucial for the development of more effective therapeutic and diagnostic agents. In the present review, we intend to compile scholarly information to explore the biological relations of nanosized hydroxyapatite with the human cellular environment and the feasible modifications that may improve the theragnostic efficacy of these molecules.
基金supported by the National Natural Science Foundation of China(grant no.21371106)and the Science&Technology Project of Liaoning Province(grant no.2015020689).
文摘To study the effect of two composition ratios of nano-hydroxyapatite and collagen(NHAC)composites on repairing alveolar bone defect of dogs.Eighteen healthy adult dogs were randomly divided into three groups.Two kinds of the NHAC composites were prepared according to the constituent ratios of 3:7 and 5:5;immediately after extraction of the mandibular second premolars,each kind of the NHAC composite was implanted into extraction socket,respectively:Group I,nHA/Col紏3:7;Group II,nHA/Col紏5:5 and Group III,blank control group.The bone-repairing ability of the two grafts was separately analyzed by morphometric measurement,X-ray tomography examination and biomechanical analysis at 1st,3rd and 6th month post-surgical,respectively.The NHAC composites were absorbed gradually after implanting into alveolar bone defect and were replaced by new bone.The ratios of new bone formation of Group I was significantly higher than that of Group II after 3 months(P<0.05).The structure and bioactive performance can be improved when the ratio between the collagen and the hydroxyapatite was reasonable,and the repairing ability and effect in extraction sockets are obviously better.
基金This work was supported by the Natural Science Basic Research Plan in Shaanxi Province of China(Program No.2019JM-520)by the Special Natural Science Foundation of Science and Technology Bureau of Xi’an City(2017CGWL23,2017CGWL26,2017CGWL27,2017CGWL28)The SEM work was done at International Center for Dielectric Research,Xi’an Jiaotong University.
文摘Development of novel biomaterials for bone regeneration is based on the sufficient bone-bonding ability,bioactivity and biocompatibility.In this study,novel flexible poly(butylene succinate)/polydimethysiloxane-modified bioactive glass/nano-hydroxyapatite(PBSu/PDMS-BG/nHA)hybrid bioceramic with various nHA concentration on the in vitro bone-like hydroxyapatite(HA)formation,biomineralization activity and osteoblast cell biocompatibility were investigated.The rapid precipitation of HA on the hybrid bioceramic surfaces was found after being immersed in simulated body fluid(SBF)for seven days.Results show that the amount of HA deposition increased with the increase of nHA concentration.The optimized PBSu/PDMS-BG/nHA hybrid bioceramic exhibited good flexibility,high biomineralization activity and good osteoblast cell biocompatibility.
基金supported by National Key Research and Develop-ment Program of China(Grant No.2018YFA0703000)OPEN Project(Grant No.BHJ17C019),National Natural Science Foundation of China(Grant No.52125501)+4 种基金Key Research Project of Shaanxi Province(Grant Nos.2020GXLH-Y-021,2021GXLH-Z-028)Guangdong Basic and Ap-plied Basic Research Foundation(Grant No.2020B1515130002)Inno-vation Cultivation Fund of the Sixth Medical Center of PLA General Hos-pital(Grant No.CXPY201913)China Postdoctoral Science Foundation Funded Project(Grant No.2021M702597)Youth Innovation Team of Shaanxi Universities and the Fundamental Research Funds for the Central Universities.
文摘In the field of dura mater repair,it is essential to employ artificial substitutes mimicking the multilayered microar-chitecture and multiple functions of native dura mater for effective neurosurgery.However,existing artificial dura mater substitutes commonly cause complications because of mismatched structural and mechanical properties as well as the lack of antibacterial activity or osteogenic capability.In this study,a triple-layered dura mater substi-tute was fabricated by electrohydrodynamic(EHD)jetting techniques,including electrospinning and melt-based EHD printing processes.Highly aligned polycaprolactone(PCL)nanofibers loaded with gentamicin sulfate(GS)were prepared by electrospinning to form the inner layer,which can mimic the aligned collagen fibers of the native dura mater.Random PCL-GS nanofibers were then deposited by electrospinning to form the middle layer.They were intended to enhance the mechanical properties of the fabricated scaffolds.The outer layer involv-ing PCL microfibers doped with nano-hydroxyapatite(nHA)at various angles was printed by the melting-based EHD method,which can enhance osteogenic capability and promote the fusion between the dura mater substi-tute and the skull.The tensile strength of the triple-layered drug-loaded biomimetic dura mater substitute was 22.42±0.89 MPa,and the elongation at break was 36.43%±2.00%.The addition of GS endowed the substitutes with an anti-infection property without influencing their cytocompatibility.Furthermore,the incorporation of nHA promoted the osteogenic differentiation of MC3T3-E1 cells seeded on the triple-layered scaffolds.This work offers a promising strategy to manufacture multilayered dura mater substitutes with the desired antibacterial and enhanced osteogenic capability performance,possibly providing a novel candidate for dural tissue repair.
基金National Natural Science Foundation of Chinagrant number:31000431 and 10925208+1 种基金Bejing Nove Programgrant number:2010B011
文摘Chitin is a kind of seemly material to match PLLA for a scaffold, which may create an appropriate environment for the regeneration of tissues. In this study, we evaluated hydrophilicity of a new nano-hydroxyapatite/collagen/PLLA (nHACP) scaffold optimized by chitin fibres for bone tissue engineering. The results show that with the CF content increase, hydrophilicity of nHACP/CF increases, which reflects from the side that the addition of the chitin fibres can improve the cytocompatibility of the nHACP. Moreover, crosslink does not take significant influences on the material hydrophilicity. The results suggest that nHACP/CF with the crosslink should be a kind of potential appropriate scaffold for tissue engineering.
