Immunomodulatory activity of polycaprolactone nanoparticles with calcium phosphate salts against Leishmania infantum infection

Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant.Methods:The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles.Particles were characterized by scanning electron microscopy and zeta potential measurements.Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis.In addition,the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method,respectively.The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum.Results:Compared to the control group,SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6-and 7-fold increase in nitric oxide,respectively.Additionally,the vaccine formulations promoted the production of IFN-γand IL-12.SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13-and 11-fold reduction in infection index,respectively,compared to the control group.Conclusions:The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties.Therefore,PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.

Polydopamine-modified metal-organic frameworks nanoparticles enhance the corrosion resistance and bioactivity of polycaprolactone coating on high-purity magnesium

Biodegradable magnesium(Mg)and its alloys exhibit excellent biocompatibility and mechanical compatibility,demonstrating tremendous potential for applications in orthopedics.However,the rapid degradation rate has limited their clinical application.Polycaprolactone(PCL)is commonly employed as a polymer coating to impede the rapid degradation of Mg.Unfortunately,its long-term anti-corrosion capability and bioactivity are inadequate.To address these issues,polydopamine(PDA)-modified zeolitic imidazolate framework-8(PZIF-8)bioactive nanoparticles are fabricated and incorporated into the PCL coating.The PZIF-8 particles,featuring catechol motifs,can enhance the compactness of the PCL coating,reduce its defects,and possess biomineralization ability,thereby effectively improving its anti-corrosive and bioactive properties.Moreover,the active substances released from the degradation of the PZIF-8 particles such as Zn^(2+)and PDA are beneficial for osteogenesis.The corrosion tests indicate that the corrosion current density of PCL-treated sample decreases by more than one order of magnitude and the amount of H_(2)released decreases from 0.23±0.12 to 0.08±0.08 ml cm^(-2)after doping with the PZIF-8.Furthermore,the improved corrosion resistance and released PDA and Zn^(2+)from the coating can promote osteogenic differentiation by up-regulating the expression of alkaline phosphatase activity,related osteogenic genes,and proteins.In addition,in vivo implantation experiments in rabbit femur defects further offer strong evidence that the doping of PZIF-8 nanoparticles accelerates bone reconstruction of the PCL coating.In summary,this work implies a new strategy to fabricate a PCL-based coating on Mg-based implants by introducing the PZIF-8 particles for orthopedic applications.

3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.

相容性蟹壳粉-PCL复合材料的制备及其力学性能

利用蟹壳这种常见的水产废弃物与生物降解性聚己内酯(PCL)熔融共混可以制得新的环境友好型复合材料,符合可持续发展理念,在复合材料的研究中拥有广阔的前景.但是蟹壳的主要成分碳酸钙具有亲水性,而PCL具有疏水性,两者结合后会出现界面相容性差的情况.实验发现,通过加入聚己内酯基聚氨酯预聚体(PCLPU)增容剂,可以解决两者界面相容性差的问题,并可通过控制PCLPU的添加比例,制成不同的蟹壳粉-PCL复合材料.再利用红外光谱、SEM、力学性能的测试数据,研究PCLPU的添加量对蟹壳粉-PCL复合材料的性能影响.实验结果表明,通过添加PCLPU,不仅可以提高蟹壳粉-PCL复合材料的界面相容性,也能够制得力学性能优良的蟹壳粉-PCL复合材料.

Preparation and Drug-Release Property of Polycaprolactone (PCL)/Polyglycolic Acid (PGA) Composite Masterbatch with Drug of Tea Polyphenols (TPs)

In order to effectively control the drug-release rate of medical textiles,biodegradable polycaprolactone(PCL) and polyglycolic acid(PGA) were blended at various mass ratios to prepare composite masterbatches for medical textiles.The surface morphology and the chemical structure of the masterbatches were analyzed.The crystallization,mass losses,strengths and drug-release rates of the composite masterbatches at different PCL/PGA mass ratios were explored.The results show that the degradation rate of the PGA carrier is obvious higher than that of the PCL carrier,and PCL,PGA and the tea polyphenol(TP) drug just physically mix without chemical reaction.During the degradation,the strength of the composite masterbatches gradually decreases.In addition,the drug-release rates of composite masterbatches at different mass ratios are different,and the more the PGA in the composite masterbatches,the faster the drug release of the composite masterbatches.The drug-release rate of the composite masterbatches can be controlled by adjusting the contents of PCL and PGA.

PCL-PEG-HAAM复合支架的构建及其对人牙周膜干细胞增殖、黏附及成骨分化的影响

目的初步探究PCL-PEG-HAAM支架的制备方法,以及复合支架对人牙周膜干细胞(PDLSCs)增殖、黏附及成骨分化的影响。方法通过生物酶/化学/机械联合的方法对人羊膜(HAM)进行脱细胞制备人脱细胞羊膜(HAAM),采用0.1%明胶作为黏附介质将聚己内酯-聚乙二醇(PCL-PEG)与HAAM整合,构建PCL-PEG-HAAM复合支架,并通过扫描电镜观察其显微结构。酶消化法培养PDLSCs,流式细胞术及多向诱导分化(成骨、成脂、成软骨)对PDLSCs进行鉴定。实验分组:Control组、PCL-PEG组、HAAM组、PCL-PEG-HAAM组,选取第3代PDLSCs分别进行CCK-8实验、BCIP/NBT染色、茜素红染色以及WB检测成骨相关蛋白(RUNX2、ALP、COL1)的表达;此外,还将第3代PDLSCs负载于PCL-PEG、HAAM、PCL-PEG-HAAM进行细胞粘附实验,通过以上实验检测PDLSCs在各组支架上的生物学性能及成骨分化的能力。结果去除羊膜上皮细胞的HAAM完整保留了基底层和致密层,扫描电镜下见基底层表面完整无剥脱,致密层胶原纤维相互交织呈多孔蜘蛛网状结构;PCL-PEG-HAAM复合支架为双层膜结构,两者间可见明显交界线,HAAM与下方呈“渔网状”的PCL-PEG纳米纤维紧密连接。CCK-8结果显示第7天时PCL-PEG-HAAM组细胞增殖速率高于PCL-PEG组(P<0.05);PCL-PEG-HAAM组的细胞粘附率高于PCL-PEG组(P<0.05);BCIP/NBT染色和茜素红染色结果显示PCL-PEG、HAAM、PCL-PEG-HAAM支架均能促进PDLSCs的成骨分化,其中,PCL-PEG-HAAM组染色面积最深最广;WB结果显示PCL-PEG-HAAM组RUNX2、COL1、ALP成骨蛋白表达量显著高于Control组、PCL-PEG组(P<0.05)。结论PCL-PEG-HAAM复合支架促进了PDLSCs增殖、黏附及成骨分化,是一种具有开发潜力的口腔生物膜。

基于PCL的钢箱节段虚拟预拼装技术

针对目前工程应用中的虚拟预拼装技术存在主观性强、自动化程度低、数据处理过程较为复杂等缺点,首次提出将PCL应用于基于点云数据的钢箱节段虚拟预拼装技术。首先根据钢箱节段截面特征设计一套由面到线、由线到点的控制点提取方法;然后基于PCL中的高效点云处理算法对待拼装截面初始点云数据进行预处理、控制点提取及匹配,输出拼装误差结果;最后将虚拟预拼装技术中使用到的算法串联成群,形成一套完整的钢箱节段虚拟预拼装程序,实现从数据输入到结果输出。将提出的虚拟预拼装技术应用于某钢箱结构桥梁相邻节段,并将计算所得最大拼装误差1.22 mm与规范规定误差进行对比分析,说明基于PCL的虚拟预拼装技术可以有效完成钢箱节段的预拼装工作,具有结果准确、自动化程度高等优点;吊装有应力状态下的节段控制点竖向位移处于0.08~0.14 mm范围内,结果表明工厂扫描得到的控制点坐标可用于指导实际工程拼装。

Preparation and properties of biodegradable bamboo powder/polycaprolactone composites

The bamboo powder/polycaprolactone composites (BPPC) were prepared by torque-rheometer to investigate the effects of recipes and processing conditions on the rheological properties of BPPC. The morphological behavior and mechanical properties of BPPC were also studied. Results showed that the optimum recipe for composite materials is composed of 70% of polycaprolactone, 30% of bamboo powder according to volume, 1.6 % of aluminate coupling agent, 1.2% of stearic acid, and 2% of paraffin to bamboo powder according to mass ratio. The optimum processing condition parameters were determined as the rotational speed at 50 r·min-1 and the temperature at 100oC for BPPC. The BPPC (containing 30 copies bamboo powder) possessed eminent interfacial compatibility and mechanical properties of BPPC.

Influence of Sorbitan Monooleate on Morphology and Drug Release Behavior of Emulsion Electrospinning Polycaprolactone Nanofibers

Ultrafine polycaprolactone(PCL)fibers containing watersoluble drug tetracycline hydrochloride(Tet)were prepared by emulsion electrospinning.Sorbitan monooleate(Span80)was added as an essential additive to form stable water/oil emulsions and fabricate fibers with core-sheath structure.Different concentrations of Span80(0-40 g/L)were used to investigate the stability of emulsion and size of dispersed droplets.The scanning electron microscope(SEM)images indicated that the morphology of the fibers with Span80 were beaded-free with diameters of 200-400 nm,and Span80 enhanced the spinnability of electrospinning solution.The laser scanning confocal microscope(LSCM)images indicated that Tet was well encapsulated into the core region of the PCL fibers.The transmission electron microscope(TEM)image showed the formation of core-sheath structure.The loading efficiency(LE)and entrapment efficiency(EE)of Tet were calculated and release profiles in artificial saliva buffer solution(pH=6.8)were also analyzed.The results revealed that LE and EE of fibers with Span80decreased with the increase of its concentration.Fibers with coresheath structure had a longer effective release lifetime than without Span80.The increase of Span80 resulted in higher hydrophilicity of fibers and faster release rate of Tet.

Processing and Mechanical Characterization of Electro-spun Polycaprolactone Membrane Coated Hernia Mesh

Composite hernia meshes designed in this paper consist of polypropylene( PP) knitted meshes and polycaprolactone( PCL)nanofiber membranes,which are produced by electro-spinning the solution composed of PCL as a solute and the mixture of dimethylformamide( DMF) and dichloromethane( DCM) as a solvent. The morphology and diameter of nanofibers in the membrane are well performed when the 15% PCL solution is electrospun under the condition of 18 k V,15 cm,0. 7 m L/h. The poresize of the membranes is less than 10 μm, where such kinds of arrangement are extremely compact to prevent the cells from growing in. The mechanical properties of the membrane with better arrangement state can reach 68. 8 c N/mm^2. The cytotoxicity test of the composite mesh demonstrates the nontoxicity of the materials.However,the bonding fastness between the membrane and the PP mesh is extremely unsubstantial. The better ways to bond PP mesh with PCL membranes should be discussed in the future.

In vitro toxicologic study of chitin short fiber reinforced polycaprolactone composite

Objective: To investigate the cytotoxicity and cytocompatibility of chitin fiber reinforced polycaprolactone composite in vitro in order to provide useful scientific basis for clinical application. Methods: Cell morphology observation, MTT and DNA assay were used to evaluate the influence of the composite on the morphology, growth and proliferation of cultured L-929 cells. Results: The composite did not impair the morphology of cultured cells in vitro. MTT and DNA assay demonstrated that the growth and proliferation of the cultured cells were not significantly inhibited by the composite. Conclusion : The composites have fine cytocompatibility and are safe for clinical use of reconstruction of chest wall defects.

Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy,11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide(poorly water soluble compound) loaded polycaprolactone(nanoDDA) was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy(SEM) and dynamic light scattering(DLS) studies. Fourier Transform InfraRed Spectroscopy(FTIR) was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-~3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes.The nano-DDA displayed spherical shape with a smooth surface(252.898 nm diameter), zeta potential, encapsulation and loading efficiencies of -38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced(FTIR analysis). Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles(Rh123-PCL NPs) revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude,our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

Preparation and properties of biodegradable bamboo powder/polycaprolactone composites

The bamboo powder/polycaprolactone composites （BPPC） were prepared by torque-rheometer to investigate the effects of recipes and processing conditions on the theological properties of BPPC. The morphological behavior and mechanical properties of BPPC were also studied. Results showed that the optimum recipe for composite materials is composed of 70% of polycaprolactone, 30% of bamboo powder according to volume, 1.6 % of aluminate coupling agent, 1.2% of stearic acid, and 2% of paraffin to bamboo powder according to mass ratio The optimum processing condition parameters were determined as the rotational speed at 50 r-min^-1 and the temperature at 100℃ for BPPC. The BPPC （containing 30 copies bamboo powder） possessed eminent interfacial compatibility and mechanical properties of BPPC.

Osteogenic composite nanocoating based on nanohydroxyapatite, strontium ranelate and polycaprolactone for titanium implants

Titanium and its alloys are commonly used as dental and bone implant materials.Biomimetic coating of titanium surfaces could improve their osteoinductive properties.In this work,we have developed a novel osteogenic composite nanocoating for titanium surfaces,which provides a natural environment for facilitating adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(MSCs).Electrospinning was used to produce composite nanofiber coatings based on polycaprolactone(PCL),nano-hydroxyapatite(nHAp)and strontium ranelate(SrRan).Thus,four types of coatings,i.e.,PCL,PCL/nHAp,PCL/SrRan,and PCL/nHAp/SrRan,were applied on titanium surfaces.To assess chemical,morphological and biological properties of the developed coatings,EDS,FTIR,XRD,XRF,SEM,AFM,in-vitro cytotoxicity and in-vitro hemocompatibility analyses were performed.Our findings have revealed that the composite nanocoatings were both cytocompatible and hemocompatible;thus PCL/HAp/SrRan composite nanofiber coating led to the highest cell viability.Osteogenic culture of MSCs on the nanocoatings led to the osteogenic differentiation of stem cells,confirmed by alkaline phosphatase activity and mineralization measurements.The findings support the notion that the proposed composite nanocoatings have the potential to promote new bone formation and enhance bone-implant integration.

The Accelerated Thermo-Oxidative Aging Characteristics of Wood Fiber/Polycaprolactone Composite:Effect of Temperature,Humidity and Time

This study investigated the characteristics of wood fiber/polycaprolactone composite after an artificial accelerated thermo-oxidative aging treatment.The effect of time,temperature and humidity during the treatment on their mechanical,chemical and morphology properties were evaluated.The composite was prepared from melted wood fibers and modified polycaprolactone by a molding process.A temperature and humidity controllable test chamber was used for the thermo-oxidative aging of the composite.The thermo-oxidative aging caused surface of the composite to be much more rougher and even a few cracks and holes appeared on it.According to the spectra of Fourier Transform Infrared(FTIR)and Gel Permeation Chromatography(GPC),C=O in the molecular chain of polycaprolactone was hydrolyzed and C–O was broken after the aging treatment,which resulted in a reduction in average molecular weight of the composite.Moreover,results showed that the mechanical strength decreased a lot with the increase in time,temperature and humidity,and the effect of temperature and humidity was more significant compared with that of time.Controlling the temperature and humidity during thermo-oxidative aging treatment could accelerate the aging of composite,which provided a quick and effective method for evaluating the aging resistance of the composite.

Synthesis of Polycaprolactone with Two Carboxyl End Groups

At 225℃. caprolactone has been polymerized in the presence of succinic acid under dry nitrogen atmosphere. Characterizations of the polymer through IR and molecular weight measurements by 1H-NMR and end group titration have shown that the polycaprolactone obtained is of two carboxyl end groups. The molecular weight of it increases with decreasing of the acid content in the reaction mixture under the same polymerization conditions. With a certain ratio of acid to caprolactone. the maximum of molecular weight of the polymer will be reached at the reaction time of 3h.

In vitro evaluation of degradation,cytocompatibility and antibacterial property of polycaprolactone/hydroxyapatite composite coating on bioresorbable magnesium alloy

Polycaprolactone/hydroxyapatite(PCL/HA)composite coating was fabricated by a combination of hydrothermal and dipping methods to delay the degradation of Mg alloy AZ31 as bioresorbable materials.The PCL/HA coating was composed of nano rod-shape HA crystals and PCL filled in the space of HA crystals.Compared with the single HA coating,the binding strength between the PCL/HA composite coating and Mg alloy was obviously improved and the PCL/HA coating still adhered to the surface of AZ31 substrate even after 38 days of immersion.The electrochemical corrosion rate of HA coated sample was reduced by ten times after being filled by PCL.The electrochemical impedance spectroscopy(EIS)and immersion test results showed that the PCL/HA composite coating could provide a more effective barrier for Mg substrate than the HA coating alone.The cytocompatibility and the antibacterial property of HA coating and PCL/HA coating were evaluated by culturing with bone marrow-derived mesenchymal stem cells(BMSCs)and methicillin-resistant staphylococcus aureus(MRSA)for 24 h under direct culture conditions,respectively.The PCL/HA composite coating showed better BMSC cell compatibility,more suitable for BMSC adhesion than HA coating alone and showed a potential application prospect as a biological materials.However,from the perspective of clinical applications,the antibacterial property of PCL/HA composite coating needs to be further improved.

Fabrication of Porous Polycaprolactone/Carboxymethylcellulose Scaffolds by using Salt Leaching Technique

The purpose of this work was to fabricate three-dimensional porous scaffolds by using the salt leaching technique.This technique is simple and it does not need the pressure or dislike expensive equipment.The study selected polycaprolactone blended with carboxymethylcellulose that is the additive.The ratios of them were derived from mixture design in Minitab program that was 98/2(P1),93.5/6.5(P2),89/11(P3),84.5/15.5(P4),and 80/20(P5),respectively.The scanning electron microscopy(SEM)was applied to assess the physical properties and the pore size dimension of the scaffold from SEM micrographs.The results of SEM present the scaffolds happened interconnected porous structures that are found in all of the P1-P5 samples.The pore size dimension of all sample scaffolds is in the range of 264.11-348.28μm.Whereas the largest and the smallest of pore size are the sample of P3 and P2,respectively,while the porosity ranges from 98.06%-98.88%that the sample of P5 is the greatest and the sample of P4 is the slightly lowest.In conclusion,the blended PCL/CMC scaffolds P1-P5 were formed by salt leaching technique suitable to use in tissue engineering application.However,the amount of CMC blended with PCL should be reasonable in order to adjust the hydrophilic of the scaffold.