Effects of friction stir processing and nano-hydroxyapatite on the microstructure,hardness,degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications

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.

Melt-Spinning of Nano-Hydroxyapatite/Poly(ε-caprolactone)Composite Fibers for Potential Application in Bone Tissue Engineering

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.

Remediation Effects of Different Concentration of Nano-Hydroxyapatite Level on Pb-Contaminated Soil

Phosphorus-containing amendments can reduce the mobility of Pb in soil. Hydroxyapatite (HAP) is one of the most commonly used phosphorus-containing amendments. With the development of nanotechnology, nano-hydroxyapatie (n-HAP) was gradually applied to remediate soil polluted by heavy metals. Considering the concentrations of HAP/n-HAP were not more than 5% in most studies, soil polluted by Pb was artificially prepared and three different concentrations of n-HAP: 5%, 7% and 10% by weight, were added into the Pb-polluted soil separately. The mixtures of soil and n-HAP were incubated for 180 d and sampled regularly. The bioaccessibility of Pb in soil was determined using simulated gastric juices of two in-vitro digestion tests: USPM (United States Pharmacopeia Methodology) and PBET (Physiologically-Based Extraction Test). The results showed that the immobilizing efficiency of 5% n-HAP to Pb in soil was the highest in PBET. The extractable Pb from soil by USPM was not affected by concentration of n-HAP. So, the least concentration of n-HAP, i.e. 5% n-HAP treatment, was the most cost-effective in USPM. Soil pH increased with concentration of n-HAP. However concentration of n-HAP had little effects on content of soil OM. According to regression analysis, more than 50% differences of the extractable Pb from soil by PBET can be explained by soil pH, while soil pH, organic matter content and incubation time together explained nearly 85% differences of extractable Pb from soil by USPM.

Improving chitosan-based composite membrane by introducing a novel hybrid functional nano-hydroxyapatite with carboxymethyl cellulose and phytic acid

A functional hybrid nano-hydroxyapatite(carboxymethyl cellulose-phytic acid-n-HA,CMC-PA-n-HA)was prepared by adding CMC and PA.The results of Fourier transformation infrared spectra,X-ray diffraction,thermal gravimetric analysis and dispersion experiments indicated that the addition of CMC and PA affected the morphology,crystallinity and crystal size of hybrid n-HA,and CMC endowed hybrid n-HA with excellent dispersion.Scanning electron microscope results showed that CMC-PA-n-HA nanoparticle could be uniformly dispersed in chitosan(CS)matrix to obtain composite membrane by casting technology,so that the highest tensile strength of CMC-PA-n-HA/CS composite membrane was 69.64%and 144.45%higher than that of CS membrane and n-HA/CS composite membrane,respectively.Contact angle test showed that CMC-PA-n-HA effectively improved hydrophilicity of the CS membrane.The simulated body fluid immersion results indicated that the CMC-PA-n-HA/CS composite membrane not only exhibited good degradability but also promoted bone-like apatite deposition.The cell proliferation experiments proved that the introduction of PA made the composite membrane have better cell adhesion and proliferation ability.Antibacterial tests demonstrated that PA could effectively improve the antibacterial properties of the composite membrane,which is expected to be applied as guide bone tissue regeneration membrane.

n-HAP/PVA共混复合纤维的制备及其结构和性能

通过凝胶纺丝法制备具有生物相容性的纳米羟基磷灰石/聚乙烯醇(n-HAP/PVA)共混复合纤维.将硅烷偶联剂修饰后的n-HAP均匀分散在PVA溶液中,制得一系列不同n-HAP质量分数的n-HAP/PVA共混复合纤维.用哈克流变仪研究了n-HAP/PVA纺丝原液的流变性能,n-HAP/PVA纺丝原液呈现非牛顿流体的特性,其剪切黏度随n-HAP质量分数的增加而增加.在傅里叶变换红外光谱(FT-IR)中可以看出n-HAP与PVA之间存在明显的氢键相互作用力,通过扫描电子显微镜(SEM)观察到n-HAP均匀地分散在PVA基体中,加入适量的n-HAP对共混复合纤维的热学性能和断裂强度都有一定的提高.

Extraction of Natural Nanostructured Hydroxyapatite from Pacific Cod(Gadus macrocephalus)Bone with a Thermostable Collagenolytic Protease and Its ex vivo Intestinal Bioavailability

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.

纳米羟基磷灰石对Cu^(2+)的吸附

用溶胶-凝胶法制备纳米羟基磷灰石(n-HAP)吸附水溶液中的铜离子(Cu2+),研究反应时间、体系pH值和Cu2+初始浓度等因素对吸附行为的影响,并探讨吸附机理。结果表明:在溶液pH=4.5~7.5,n-HAP对Cu2+的吸附升高趋势近似线性关系;反应60 min时基本达到吸附平衡;pH>7.5时,溶液中Cu2+几乎完全去除,最大吸附量为51.28 mg/g。n-HAP对Cu2+有良好的吸附作用,吸附类型为Langmu ir等温吸附,吸附过程符合拟二级反应动力学方程。

纳米羟基磷灰石/壳聚糖-海藻酸钠复合材料的制备及性能研究

目的研究合理人工骨三元复合生物材料的制备及性能。方法采用共沉淀法制备了纳米羟基磷灰石/壳聚糖-海藻酸钠(n-HAP/CS-ALG)三元复合材料,用XRD、SEM、TEM和IR对材料性能进行表征。结果纳米羟基磷灰石/壳聚糖-海藻酸钠的比例为70/30时形成的复合材料中,n-HAP在有机相中分散均匀,并与有机相发生作用,界面结合牢固;复合材料中的n-HAP呈弱结晶状态,有较高生物活性。壳聚糖和海藻酸钠发生聚合,聚合物对材料起到增强作用。结论该复合材料可望作为骨组织替代材料。

Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells

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.

Comparative evaluation of the physicochemical properties of nano-hydroxyapatite/collagen and natural bone ceramic/collagen scaffolds and their osteogenesis-promoting effect on MC3T3-E1 cells

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.

Magnesium/Nano-hydroxyapatite Composite for Bone Reconstruction: The Effect of Processing Method

Nano-ceramic particles can serve as reinforcing agents for metallic materials to improve their mechanical properties.However,it is important to ensure chemical compatibility between the matrix and particles.In the present study,magnesium composites with and without nano-hydroxyapatite(nHA)particles were fabricated for bone reconstruction applications.Two different techniques were used,Conventional Sintering(CS)of powder compacts and Spark Plasma Sintering(SPS)of pre-compacted powder.Results showed that a 10 wt%addition of nHA particles to magnesium,followed by SPS improved the compression strength by 27%.CS did not lead to any significant improvement compared to SPS processing.X-ray diffraction data after CS revealed the formation of unfavorable phases due to chemical reactions between nHA particles and the magnesium matrix,while these phases were absent after SPS processing.The mechanical properties of the specimens fabricated by CS were much inferior to those processed using SPS.The shorter processing time associated with SPS leaded to reduced interaction between nHA particles and the Mg-matrix,compared to CS.

Nano-hydroxyapatite(n-HA)involved in the regeneration of rat nerve injury triggered by overloading stretch

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.

Blood Compatibility of Nano-Hydroxyapatite Dispersed Using Various Agents

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.

Advancements of Nano-Hydroxyapatite in Sports Medicine from Bone Injury Perspectives

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.

Effect of Antibacterial Enoxacin on the Properties of Injectable Nano-hydroxyapatite/Polyurethane Cement for Bone Repairing

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.

A Brief Review on Hydroxyapatite Nanoparticles Interactions with Biological Constituents

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.

A Novel Open C-shaped Molar Band for Orthodontic Applications： Mechanical Characterizations and Clinical Trials

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.

Comparison of bone regeneration in alveolar bone of dogs on mineralized collagen grafts with two composition ratios of nanohydroxyapatite and collagen

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.

Flexible organic-inorganic hybrid bioceramic for bone tissue regeneration

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.

Electrohydrodynamic Fabrication of Triple-layered Polycaprolactone Dura Mater Substitute with Antibacterial and Enhanced Osteogenic Capability

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.