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.

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.

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.

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.

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.

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.

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.

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.

Development of Polycaprolactone/Poly(Vinyl Alcohol)/Clay Microparticles by Spray Drying

In this study, nanostructured microparticles was developed with polycaprolactone (PCL), poly(vinyl alcohol) (PVAL) and nanoparticles of the commercial sodium clay NT-25®by using the spray drying technique. The systems obtained were characterized by Nuclear Magnetic Resonance (NMR), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Dynamic Laser Light Scattering (DLS) and Differential Scanning Calorimetry (DSC). The NMR 13C and FTIR techniques showed that both polymers were present in the microparticles and the DSC analysis revealed a small variation in the glass transition temperature of the PCL. The XRD and SEM analyses showed that the microparticles produced were amorphous and had a concave morphology. The NT-25 nanoload reduced the microparticles’ size due to the multiple interactions formed in the hybrid nanocomposite material. Therefore, it was possible to develop microparticles by using biodegradable and biocompatible polymers, with different polarities, allowing the incorporation of hydrophilic and hydrophobic materials and enabling the inclusion of otherwise incompatible materials in the same system.

POLYCAPROLACTONE-POLY (ETHYLENE GLYCOL) BLOCK COPOLYMER Ⅲ DRUG RELEASE BEHAVIOR

The drug release behavior of degradable polymer--polycaprolactone-poly (ethyleneglycol)block copolymer(PCE) in vitro was investigated by using 5-Fluoro-uracil (5-Fu) asa model drug under a condition of pH 7. 4 at 37C. It is found that the release rate of 5-Fufrom PCE increased with increasing polyether content of the copolymer. The results showthat the increasing polyether content of the copolymer caused increasing hydrophilicity anddecreasing crystallinity of the PCE copolymer. Thus, the drug release behavior and thedegradable property of the PCE can be controlled by adjusting the composition of thecopolymer.

Enzymatic Synthesis of Polycaprolactone:Effect of Immobilization Mechanism of CALB on Polycaprolactone Synthesis

Surface-modified rice husk ash was used as an inorganic support material for immobilization of Candida antarctica lipase B.(3-aminopropyl)trimethoxysilane was used for surface modification.Immobilization of CALB was performed via both physical adsorption and cross-linking.PCL synthesis was carried out by using these immobilized enzymes,free enzyme and Novozyme 435®.Molecular weight distribution of polymer samples was obtained by gel permeation chromatography(GPC)and chain structures of the polymer samples were observed by hydrogen nuclear magnetic resonance(1H-NMR).The highest monomer conversion is generally obtained by using cross-linked enzyme,around 90%.PDI values for all polymer samples were approximately 1.5 which can be considered as acceptable.In general cross-linked enzymes were better than physically adsorbed enzymes in terms of average molecular weights.It can be concluded that PCL can be synthesized with these immobilized enzymes with high molecular weight and low PDI values.

Photodegradation Behavior of Polycaprolactone-Poly(ethylene glycol)Block Copolymer

The biodegradation behavior in vitro and in vivo of polycaprolactone-poly (ethylene glycol) block copolymer (PCE) was reported in detail. In this paper, photodegradation test of PCE was performed by exposure to UV light. The mechanical properties and the inherent viscosity of PCE samples which are subjected to photodegradation were determined. The experimental results indicated that poly (ethylene glycol) (PEO) segment in PCE copolymer is photosensitive. The photodegra-dation rate of the PCE was increased with increasing poly (ethylene glycol) content.

Comparison of Release Efficiencies for the Controlled-Release of Potassium Permanganate in Polycaprolactone

The application of controlled release materials in tandem with chemical oxidants has become an emerging topic within the field of environmental treatment. The controlled release kinetic and mechanistic relationship between these components is important to understand a controlled release system. Potassium permanganate (KMnO4) was used as the encapsulated material integrated into polycaprolactone (PCL) producing controlled release biodegradable polymer (CRBP) pellets. In this study, batch experiments were used to examine the release kinetics from the discharge of the pelletized encapsulated oxidant into aqueous systems at various KMnO4:PCL ratios of 1:5, 2:5, and 3:5 by mass. Experimental results indicated as the amount of KMnO4 in the PCL polymer pellets increased, a greater fraction of the oxidant was released as a function of time. The resultant data best fit a linearized diffusion model equation. Additionally, a comparison-controlled release study was conducted that contained the same oxidant at similar mass ratios. Release kinetics determined from this study could lead to effective implementation of CRBP systems and could suggest that CRBP encapsulated with KMnO4 could serve as a promising controlled release technology in a long-term and controlled manner.

Evaluation of Nevirapine Release Kinetics from Polycaprolactone Hybrids

The Nevirapine (NVP)/Polycaprolactone (PCL)/Nanoparticles hybrids systems have been developed as a potential platform for drug delivery, by solvent cast, as thin films. NVP, an antiretroviral drug, was included within PCL matrix containing three types of nanoparticles: an organoclay layered silicate Viscogel S7®(3% w/w), hydrophilic silica oxide particles Aerosil®A20 (0.25% w/w) and titanium dioxide particles (0.25% w/w). These systems were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), low-field nuclear magnetic resonance (NMR), ultraviolet-visible spectroscopy (UV), in-vitro dissolution testing and drug release mechanism kinetics. The PCL crystallization was affected by NVP incorporation, modifying its semi-crystalline structure to a less ordered structure. When nanoparticles and NVP were added, the T1H values increased, for PCL, PCL/S7, PCL/ SiO2 and PCL/TiO2 hybrids, suggesting that its addition produced a new material, with less molecular mobility, due to the new intermolecular interactions formation. It can consider a structure formation among the PCL chains, nanoparticles and NVP, with strong forces in the PCL/SiO2/NVP system. The amount of NVP included was around 1.5 ± 0.03 mg/cm2. In the in-vitro dissolution test, the PCL/SiO2/NVP system released the smallest amount of drug and this result could be attributed to the strong intermolecular interaction between the drug and the PCL/SiO2 system. Higuchi’s model was the mathematical model chosen to treat the release data, since this model presented the highest coefficient correlation (r) value. The drug release probably occur by diffusion through the matrix pores, thus, these materials are suitable for sustained release of NVP.

The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of drugs.In this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the samples.Furthermore,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were evaluated.The microstructural observation of the scaffolds reported interconnected pores with 150–300µm in diameter.The 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D scaffolds.SPL release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th day.In addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved significantly.These findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

Injection molding of highly filled microcrystalline cellulose/polycaprolactone composites with the aid of reversible Diels-Alder reaction

To tackle the challenge of producing highly filled polymer composites using the traditional injection molding technique,which is characterized by the fairly high melt viscosity that makes mold filling difficult,the authors propose a solution based on dynamic covalent chemistry.As demonstrated by the proof-of-concept experiments,the 4-arm starshaped polycaprolactone(PCL)oligomers and microcrystalline cel-lulose(MCC)are crosslinked by the reversible Diels-Alder(DA)bonds.The flowability of the compounds greatly decreases due to the dissociation of the intercomponent DA bonds at the retro-reaction tempera-ture,and the networked architecture is reconstructed during cooling as a result of the forward DA reaction.Consequently,the high-loading MCC fillers are well distributed in the matrix and covalently bonded to the nearby PCL,forming a striking contrast to the control in which linear PCL acts as the matrix.The DA bonds crosslinked biodegradable PCL composites exhibit decent mechanical strength(20.7 MPa)even at the MCC fraction of 65 wt%,which is superior to those(5-12.2 MPa)of the highly filled PCL composites(with filler contents of 50-63.8 wt%)reported so far.The proposed approach has sufficient expansibility for the fabrication of the highly filled polymer composites constructed by other types of matrix and fillers.

Dysprosium oxide,alumina,and graphene oxide reinforced polycaprolactone thin films:Thermal stability,morphology,and cell viability

Developing a biomaterial for wound healing applications is still a challenge.Herein,dysprosium oxide(Dy_(2)O_(3)),aluminum oxide(Al_(2)O_(3)),and graphene oxide(GO)were embedded in cast films based on polycaprolactone(PCL)to be examined for wound dressing usage.Different techniques were used to characterize the fabricated films including X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FTIR),Raman,and scanning electron microscopy(SEM),besides their biological activity.The thermogravimetric analysis(TGA)exhibits high thermal stability as the scaffold weight decreases slightly to 98.6%after raising the temperature from room temperature to 280℃.The cell viability was investigated and it is shown that the viable cells grow up to approximately 93%at 75μg/mL.Meanwhile,the cell attachment shows excellent behavior as the cells attach on most of the surface of the modified PCL which shows high biocompatibility.

Surface morphology and cell viability of samarium(Ⅲ) oxide/chromium(Ⅲ) oxide/graphene oxide/polycaprolactone targeting wound dressing

Combinations of metal and lanthanide oxides have been done through casted films for potential medical applications. In this regard, samarium(Ⅲ) oxide/chromium(Ⅲ) oxide/graphene oxide(GO)/polycaprolactone(PCL) based films nano-composites(NCs) were fabricated, pointing their utilization as a biological scaffold for wound dressing purposes. Also, samarium(Ⅲ) oxide and chromium(Ⅲ) oxide have been merged as promising optical constituents due to their unique optical behavior. The structural and compositional examination of the studied NCs was executed by X-ray diffraction(XRD), Raman, and field emission scanning electron microscopy(FESEM). The Sm_(2)O_(3)/Cr_(2)O_(3)/GO/PCL NC exhibits a surface with a lower roughness degree owing to the presence of GO. Cr_(2)O_(3)shows size reduction upon GO insertion to reach 1.2 μm as the average grain size, whilst Sm_(2)O_(3)records an average grain size of less than 1 μm. As well, the polymeric nano-compositions exhibit variation in contact angle values that hit 29.76°± 3.52°for Sm_(2)O_(3)/PCL, and 48.62°± 1.37°for Sm_(2)O_(3)/Cr_(2)O_(3)/GO/PCL as the second lowest contact angle. The optical behavior contributes to absorption edge relocation along the x-axis from 1.7 eV for pure PCL, to 2.65 eV for Sm_(2)O_(3)/Cr_(2)O_(3)/GO/PCL. Regarding biological responses, the cell exposed to 2.5 μg/m L of Sm_(2)O_(3)/Cr_(2)O_(3)/GO/PCL shows cell viability of 119.31%, while 5 μg/m L hits 99.6%. Additionally, the resulting cell attachment micrographs show layers of fibroblast tissue, besides the proliferation and growth of cultivated cells. Thus, the Sm_(2)O_(3)/Cr_(2)O_(3)/GO/PCL scaffold provides 3D proliferation of fibroblast cells endorsing the wound healing process.

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.