Electrospun Small Diameter Tubes to Mimic Mechanical Properties of Native Blood Vessels Using Poly (L-lactide-co-ε-caprolactone )and Silk Fibroin: a Preliminary Study

Mismatch in mechanical properties can induce intimal hyperplasia,which is one of the main reasons for the failure of small diameter artificial blood vessels. Electrospun small diameter tubes with tailored mechanical properties were fabricated through blending poly( L-lactide-co-ε-caprolactone)( PLCL) and silk fibroin( SF)with the mass ratios of 30 /70,50 /50,and 70 /30 in this study.Scanning electron microscopy( SEM) and mechanical testing were used to characterize morphological and mechanical properties of the tubes. Results showed that tensile strength of the tubes was higher than most of the native blood vessels,and elongations at break of them were improved greatly by blending PLCL. Compliances of the tubes were all higher than 1% /13. 33 kPa( 1% /100 mmHg).Particularly,tubes with blending mass ratio of 50 /50 showed similar compliance with human native femoral arteries,which provided a promising biomaterial that could be applied on small diameter vascular applications.

“Polymer-in-ceramic” based poly(ε-caprolactone)/ceramic composite electrolyte for all-solid-state batteries

Inspired by the concept of "polymer-in-ceramic",a composite poly(ε-caprolactone)(PCL)/ceramic containing LiTFSI is prepared and investigated as a solid electrolyte for all-solid-state batteries.The composite with the optimum concentration of 45 wt% LiTFSI and 75 wt% Li1.5Al0.5Ge1.5(PO4)3(LAGP,NASICON-type structure) exhibits a high ionic conductivity(σi=0.17 mS cm-1) at 30℃,a transference number of 0.30,and is stable up to 5.0 V.The composite electrolyte is a flexible and self-standing membrane.Solid-state LiFePO4//Li batteries with this composite electrolyte demonstrate excellent cycling stability with high discharge capacity of 157 mA h g-1,high capacity retention of 96% and coulombic efficiency of 98.5% after 130 cycles at 30℃ and 0.1 C rate.These electrochemical properties are better than other PCL-based allsolid-lithium batteries,and validate the concept of "polymer-in-ceramic" by avoiding the drawback of lower conductivity in prior "polymer-in-ceramic" electrolyte at high concentration of the ceramic.

PREPARATION AND CHARACTERIZATION OF INCLUSION COMPLEXES OF TWO-ARM LINEAR AND FOUR-ARM STAR-SHAPED POLY(ε-CAPROLACTONE)S WITHα-CYCLODEXTRIN

Both four-ann star-shaped poly（ε-caprolactone） （4sPCL） and two-ann linear PCL （2LPCL） were synthesized and their inclusion complexation with α-cyclodextrin （α-CD） were studied. The inclusion complexes （ICs） formed between the PCL polymers and α-CD were characterized by ^1H-NMR, DSC, TGA, WAXD, and FT-1R, respectively. Both branch ann number and molecular weight of the PCL polymers have apparent effect on the stoichiometry （CL：CD, mol：mol） of these ICs. All these analytical results indicate that the branch arms of the PCL polymers are incorporated into the hydrophobic α-CD cavities and their original crystalline properties are completely suppressed. Moreover, the inclusion complexation between two-ann linear or four-ann star-shaped PCL polymers and α-CD not only enhances the thermal stability of the guest PCL polymers but also improves that of α-CD.

Structure Changes of Silk Fibroin(SF) by Blending with Poly(ε-caprolactone)(PCL):Characterization of SF and PCL Blended Electrospinning Films

The mechanical properties and water solubility of electrospinning SF films limit their use as biomaterials. In order to develop a tissue engineering biomaterial with both satisfying biological properties and sufficient biomechanical properties,blended films composed of silk fibroin( SF) and poly( ε-caprolactone)( PCL) were fabricated by electrospinning in this study. Scanning electron microscope( SEM), X-ray diffraction( XRD),thermal analysis,Fourier transform-infrared( FT-IR),Raman spectra,mechanical testing,and water solubility were used to characterize the morphological, structural and mechanical properties of the blended electrospinning films. Results showed that the diameter of the blended fiber was distributed between 600 and1000 nm,and the fiber diameter increased as the PCL content increased. There is no obvious phase separation due to the similarity and intermiscibility,as well as the interactions( mainly hydrogen bonds), between the two polymers. Meanwhile, the secondary structures of SF changed from random coils and Silk I to Silk II because of the interactions between SF and PCL. For this reason,the tensile strength and elongation at break of the electrospinning films improved significantly,and the water solubility decreased. In conclusion,the blended electrospinning films fabricated in this study showed satisfying mechanical properties and water insolubilities,and they may be promising biomaterials for applications in tissue engineering for blood vessels,nerve conduits,tendons,ligaments and other tissues.

Effect of Poly(ε-caprolactone-b-tetrahydrofuran)Triblock Copolymer Concentration on Morphological,Thermal and Mechanical Properties of Immiscible PLA/PCL Blends

In this study a low molecular weight triblock copolymer derived fromε-caprolactone and tetrahydrofuran was used as a non-reactive compatibilizer of immiscible PLA/PCL blends.Ternary blends with 0,1.5 wt%,3 wt%and 5 wt% copolymer and about 75 wt%PLA were prepared by single screw extrusion and characterized by scanning electron microscopy(SEM),differential scanning calorimetry(DSC),dynamic mechanical analysis(DMA),tensile and Izod impact testing.SEM micrographs showed that the size of the dispersed PCL domains was practically constant regardless of copolymer concentration.This result can be explained by the low shear rate employed during processing step and a decrease of PCL viscosity by presence of the triblock copolymer.However,when the copolymer concentration increased,strain at break of PLA/PCL blends also increased.PLA/PCL blend with 0 wt% copolymer presented 2%strain at break,whereas PLA/PCL blend with 5 wt%copolymer exhibited 90%.

MOLECULAR WEIGHT DEPENDENCE OF THE MELTING BEHAVIOR OF POLY(ε-CAPROLACTONE)

Poly(ε-caprolactone) (PCL) with different molecular weights was synthesized and characterized by a gelpermeation chromatograph equipped with multiple detector. The melting behavior of PCL was also studied. It was found thatthe equilibrium melting points (T_m^0) of PCL samples depend on their molecular weights. Wide angle X-ray diffractionmeasurements (WAXD) and DSC measurements showed that the crystals of the high molecular weight PCLs were moreperfect than those of the low molecular weigh ones. These results demonstrate that the concentration of the end groups ofPCL chains is the main factor that influences the melting behavior. The fusion enthalpy per repeating unit (ΔH_u) wasdetermined to be 11.3 kJ/mol for PCL.

HETEROCYCLIC SCHIFF BASE NEODYMIUM COMPLEX AS CATALYST FOR RING-OPENING POLYMERIZATION OF ε-CAPROLACTONE

An aromatic heterocyclic Schiff base neodymium complex bearing thiazole was synthesized and its activity in the ring-opening polymerization ofε-caprolactone(CL)was examined.The conditions of the CL/Nd molar ratio,monomer concentration,polymerization time and temperature were investigated.Activities of ca.171 kg/Nd·h were obtained under the optimum condition(CL/Nd=1600(molar ratio),[CL]=2.26 mol L^(-1),1 h at 50℃),giving a poly(ε-caprolactone)(PCL)of number-average molecular weight M_n=5.4×10~4 and molecular...

Novel electrospun poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits for repair of peripheral nerve injury

Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.

AN APPROACH TO SYNTHESIZE POLY(ETHYLENE GLYCOL)-b-POLY(ε-CAPROLACTONE) WITH TERMINAL AMINO GROUP via SCHIFF'S BASE AS AN INITIATOR

A new method to synthesize a degradable terminal amino group-containing copolymer,poly(ethylene glycol)-b- poly(ε-caprolactone)(MPEG-PCL-NH_2),was developed in the following three steps:(1)the ring-opening polymerization (ROP)ofε-caprolactone from the Schiff base prepared from benzatdehyde and ethanolamine(Ph-CH=NCH_2CH_2OH)used as an initiator to obtain heterobifunctional poly(ε-caprolactone)with one terminal Schiff base group and one hydroxyl group (HO-PCL-CH_2CH_2N=CH-Ph);(2)the coupling reaction of two ...

TRANSESTERIFICATION OF POLY(ETHYLENE TEREPHTHALATE) WITH POLY(ε-CAPROLACTONE)

Transesterification of poly（ethylene terephthalate） （PET） with poly（ε-caprolactone） （PCL） was investigated bymeans of NMR spectroscopy, extraction experiments, differential scanning calorimetry （DSC） and phase contrast microscopy（PCM）. The;H-NMR results show that transesterification takes place in the melt blends and leads to the formation of thePET-PCL copolyester with a chemical structure similar to ethylene terephthalate-ε-caprolactonc copolycster （TCL）synthesized directly from monomers. However, even in the blend that has been transesterified for 8 h, the random PET-PCLcopolyester, PET-PCL copolyester with long PET or long PCL segments and the unreacted PET and PCL homopolymersmay coexist. Due to the low mobility of PET and PCL chains and the high viscosity of the two macromolecules, thetransesterification proceeds with difficulty. Furthermore, PET is incompatible with PCL, the transesterification can onlyoccur at the interface or in the interfacial region between two phases, and finally the reaction can only reach a localequilibrium. These results indicate that in fact the transesterification in the melt blend between two incompatiblehomopolymers could not lead to the formation of completely random or typical block copolyesters.

Synthesis and Characterization of ABBA Block Copolymer of Glycolide and ε-Caprolactone

A biodegradable ABBA block copolymer was synthesized via the ring-opening co-polymerization of ~ε-caprolactone(CL, B) and glycolide(A) by means of step polymerization in the presence of ethylene glycol as an initiator and stannous octanoate as a catalyst at 110 ℃ for 48 h. The molecular length of the PCL pre-polymer(BB) could be adjusted by controlling the molar ratio of the ethylene glycol initiator to ε-caprolactone monomer. The structure and the composition of the block copolymer were determined by the weight ratio of the monomer glycolide(A) to PCL pre-polymer(BB). The block copolymers were characterized by ~ 1H NMR, GPC, DSC and X-ray. The results confirm the successful synthesis of an ABBA block copolymer.

Synthesis of Highly Branched Poly(ε-caprolactone) by Self-condensing Atom Transfer Radical Polymerization of Macroinimers

Branched poly（ε-capmlactone） was synthesized by self-condensing atom transfer radical polymerization of macroinimer, α-acryloyoxy-ω-2-bromopropionyloxy poly（ε-caprolactone）, which was prepared by enzyme-catalyzed ring-opening polymerization of ε-caprolactone with 2-hydroxylethyl acrylate as initiator and esterification of the ω-hydroxyl group of the obtained poly（ε-caprolactone） by 2-bromopropionyl bromide.

Study on two kinds of degradation mechanisms for biomaterials poly(ε-caprolactone)

The in vitro and in vivo degradation behaviour of poly (ε-caprolactone) (PCL) has been examined in terms of degree of degradation and morphological change during an inclibation period of up to 300 d. Gel permeation chromatography (GPC) and differential scanning calorimetry (DSC) were employed to character ize their degradation profiles. The observation of the changes in intrinsic viscosity and average molecular weight as well as the crystallinity of PCL leads to the findings that 2 degradation mechanisms of PCL exist. The subcutaneous implant test shows that the rate of degradation in the rabbit body is much higher than in vitro. This illustrated that in vivo, the mechanism of bioerosion is more important than hydrolytic cleavage of ester linkage, especially in the second stage of degradation. Regardless of the initial Mn of specimens, a lin ear relationship between Mn and degradation time has been observed until the Mn decreased to be about 5 ooo D. Above this figure, the main degradation mechanism was hydrolytic cleavage of ester group accompa nied by enzymatic surface erosion, below this point, the bioerosion with weight loss plays a more significant role than hydrolytic reaction in their degradation. Comparison between the morphology of PCL materials af ter and before erosion was made by means of scanning electron microscopy (SEM).

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

Nano-hydroxyapatite/poly（e-caprolactone） （nHA/PCL） composite materials are among the best candidates for application in bone tissue engineering. As the main technique to fabricate porous scaffolds, electrospilming produce scaffolds with unsatisfactory mechanical strength and limited pore size for cdi infiltration. Micron-sized fiber assembly with higher mechanical strength is qualified to structure hybrid scaffolds. In this study, nHA/PCL monofilament fibers with different mass ratios were fabricated through melt-spinning. Transmission electron microscope （TEM） was used to observe the aggregation between nHA parfides. 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 nHA/PCL composite fibers, respectively. The influence of nHA/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 partides in the polymer matrix. Besides, nHA content increases the tensile strength, initial modulus and hydrophillcity 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.

Enhanced angiogenesis in porous poly(ε-caprolactone)scaffolds fortified with methacrylated hyaluronic acid hydrogel after subcutaneous transplantation

A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-caprolactone)(PCL)and methacrylated hyaluronic acid(MeHA)hydrogel and describes the corresponding physical properties(surface area,porosity,and mechanical strength)and host response(angiogenesis and fibrosis)after subcutaneous transplantation.Specifically,we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities.Subsequently,we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds.In experiments with mice,the scaffold composed of 3%PCL and 10-100 kDa,degree of substitution 70%MeHA results in the least fibrosis and a higher degree of angiogenesis.This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation,given their desirable physical properties and host response.

Preparation and shape memory properties of TiO_2/PLCL biodegradable polymer nanocomposites

The preparation of TiO2/poly（L-lactide-co-ε-caprolactone）（PLCL） nanocomposites and their properties were reported.TiO2nanoparticles were surface modified by ring-opening polymerization of ε-caprolactone（ε-CL）.The resulting poly（ε-caprolactone）-grafted TiO2（g-TiO2） was characterized by Fourier transform infrared spectroscopy（FTIR）,thermogravimetric analysis（TGA） and transmission electron microscopy（TEM）.The g-TiO2can be uniformly dispersed in chloroform and the g-TiO2/PLCL nanocomposites were successfully fabricated through solvent-casting method.The effects of the content of g-TiO2nanoparticles on tensile properties and shape memory properties were investigated.A significant improvement in the tensile properties of the 5% g-TiO2/PLCL mass fraction nanocomposite is obtained：an increase of 113% in the tensile strength and an increase of 11% in the elongation at break over pure PLCL polymer.The g-TiO2/PLCL nanocomposites with a certain amount of g-TiO2content have better shape memory properties than pure PLCL polymer.The g-TiO2nanoparticles play an additional physical crosslinks which are contributed to improvement of the shape memory properties.

The Development and Characterization of Polycaprolactone and Titanium Dioxide Hybrids

Organic/Inorganic hybrid materials have been attracting much attention since they combine the advantages of inorganic materials with the properties of organic polymers. Titanium dioxide nanoparticles (TiO2) present good thermal stability, accessibility and catalytic properties. Polycaprolactone (PCL) is a bi-ocompatible and bioresorbable material, which is being examined as biode-gradable packaging materials, controlled drug release carriers and other medical applications. Hybrids based on PCL containing different amounts of titanium dioxide nanoparticles, ranging from 0.05% to 0.35% w/w, were prepared using the solution cast method. These systems were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), low-field nuclear magnetic resonance (NMR), thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The FTIR analysis confirmed that there was an interaction between the PCL chains and the TiO2 nanoparticles. The XRD and DSC analysis showed that the PCL crystallization was affected by TiO2 incorporation, modifying its semi-crystalline structure to a less ordered structure. When TiO2 nanoparticles were added the values of T1H and T1ρH increased for all hybrids, therefore, their addition produced a new material with less molecular mobility. In the TG analysis, it was observed that the introduction of TiO2 nanoparticles decreased the thermal resistance of PCL. In DSC analysis, the PCL/TiO2 hybrids presented a reduction in the crystallization temperature and degree of crystallinity, except for PCL hybrids containing 0.15% w/w of TiO2 nanoparticles.

Facile Synthesis of Functional Poly (ε-caprolactone) via Janus Polymerization

Functionalized aliphatic polyesters attract increasing attentions as biocompatible and biodegradable polymers with broad applications in biological science. In this contribution, we propose a facile and controllable synthetic technique for functional poly(ε-caprolactone)(PCL) via Janus polymerization, which comprises cationic ring-opening copolymerization (ROP) of ε-caprolactone (CL) with 3,3-bis(chloromethyl)oxacyclobutane (CO) and (coordinated) anionic ROP of CL at a single propagating chain by rare earth metal triflates (RE(OTf)3)and propylene oxide, thus generating block copolymers in one step. The compositions of the copolymers of poly(CLb-(CL-r-CO)) can be modulated by various RE(OTf)3. Scandium triflate catalyzes Janus polymerization to yield the copolymers containing the highest CO contents among all the RE(OTf)3 catalysts used with complete conversion of CL. The chlorine in CO repeating units is ready to be transferred into azide group which affords the modification sites to react with 9-ethynyl-9-fluorenol and mPEG-alkyne, respectively, via copper(I)-catalyzed azide-alkyne cycloaddition reaction with quantitative conversions of azides, as confirmed by FTIR analyses. According to NMR and SEC analyses, copolymers (PCC-g-PEG) bearing a homo-PCL block and a PEG-grafted block of poly(CO-co-CL) demonstrate well-defined chemical structures. The investigations on thermal properties reveal the strong phase separation between PCL and PEG blocks. The amphiphilic PCC-g-PEG is able to sei住assemble into micelles in aqueous solution while cylindrical and lamellar morphologies are observed in bulk. We provide an efficient protocol to synthesize functional PCL combining onestep Janus polymerization and precise post-polymerization click reaction.

Preparation of Poly(ε-caprolactone)/Poly(ester amide)Electrospun Membranes for Vascular Repair

With adjustable amphiphilicity and anionic/cationic charge,biodegradability and biocompatibility,amino acid-based poly(ester amide)s(PEAs)have drawn attention in the research of tissue engineered vascular grafts.In this work,L-phenylalanine-based PEAs with or without L-lysine were synthesized through polycondensation,and ultrafine fibrous grafts consisted of PEAs and poly(ε-caprolactone)(PCL)in given mass ratios were further prepared via blend electrospinning.Surface characterizations by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the chemical structure,and the wettability indicated that the prepared PCL/PEAs electrospun membranes exhibited less hydrophobic than PCL.Tensile results showed that the PCL/PEAs membranes possessed suitable mechanical properties,which could meet the requirements of artificial blood vessels.Cell culture and hemolytic tests exhibited that the PCL/PEAs electrospun membranes are biocompatible.In general,the electrospun grafts of PCL/PEAs could be applied for vascular repair.

Fabrication of shish-kebab-structured carbon nanotube/poly(ε-caprolactone) composite nanofibers for potential tissue engineering applications

The electrospinning process was applied to fabricate the nanofibers of biodegradable poly(ε-caprolactone)(PCL) in which different contents of multiwalled carbon nanotubes(MWCNTs) were embedded. Afterward,the electrospun nanofibers were successfully decorated with shish-kebab structure via a self-induced crystallization technique. The topographical features and the mechanical properties of the composite scaffolds were characterized,and the biocompatibility of the material was assessed by using human osteogenic sarcoma osteoblasts(MG-63 cells). The carbon nanotube(CNT) concentration is found to affect the fiber diameter and mechanical properties of electrospun nanofibers and the periodic distance of the shish-kebab architecture. Cellular attachment and proliferation assays reveal that 0.5 wt% CNT-embedded PCL scaffold shows enhanced biocompatibility with MG-63 cells than their counterparts made of neat PCL, and the collagen-like nanotopology provided by the shish-kebab structure further facilitates the cell adhesion and proliferation. The superior interactions between cells and scaffolds demonstrate that the shish-kebab-structured CNTs/PCL nanofibers may be promising candidate for tissue engineering scaffold application.