Viscoelastic properties of poly(ε‐caprolactone) – hydroxyapatite micro‐ and nano‐composites

Various composites have been proposed in the literature for the fabrication of bioscaffolds for bone tissue engineering. These materials include poly(ε‐caprolactone) (PCL) with hydroxyapatite (HA). Since the biomaterial acts as the medium that transfers mechanical signals from the body to the cells, the fundamental properties of the biomaterials should be characterized. Furthermore, in order to control the processing of these materials into scaffolds, the characterization of the fundamental properties is also necessary. In this study, the physical, thermal, mechanical, and viscoelastic properties of the PCL‐HA micro‐ and nano‐composites were characterized. Although the addition of filler particles increased the compressive modulus by up to 450%, the thermal and viscoelastic properties were unaffected. Furthermore, although the presence of water plasticized the polymer, the viscoelastic behavior was only minimally affected. Testing the composites under various conditions showed that the addition of HA can strengthen PCL without changing its viscoelastic response. The results found in this study can be used to further understand and approximate the time‐dependent behavior of scaffolds for bone tissue engineering. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis and characterization of polycaprolactone (B)–poly(lactide‐co‐glycolide) (A) ABA block copolymer

Novel poly(lactide‐co‐glycolide) (PLGA)/polycaprolactone (PCL) ABA block copolymers were synthesized by bulk copolymerization of glycolide and lactide with PCL diols prepolymer using stannous octoate as catalyst. The resulting copolymers were characterized by various analytical techniques including gel permeation chromatography, IR, ¹H nuclear magnetic resonance, differential scanning calorimeter and X‐ray diffractometry. Mechanical properties and hydrophilicity of the copolymers were also studied. Data showed that the copolymers presented a part‐regular structure, containing both PCL crystalline and amorphous PLGA domains. The properties of these copolymers can be adjusted by changing the compositions of the copolymers. Copyright © 2000 John Wiley & Sons, Ltd.     

Gamma irradiation of electrospun poly(ε‐caprolactone) fibers affects material properties but not cell response

Fabrication of electrospun fibrous scaffolds as future medical devices is being widely researched, with particular emphasis given to their material properties and effect on cell response and differentiation. However, the vast majority of these scaffolds are sterilized via nonmedically approved methods, including submersion in ethanol and exposure to UV light. Although these techniques are adequate for laboratory‐based research, they are not sufficient for human implantation. In this case, regulatory approved, medical grade sterilization is required. In this study, we report the effects of gamma irradiation, a regulatory approved technique, on electrospun poly(ε‐caprolactone) fibers. Fabricated fibers were separately subjected to different dosages of irradiation ranging from 0 to 45 kGy and then assessed for their physicochemical properties. Gamma irradiation affected fiber properties irrespective of dosage. A dose‐dependent decrease in polymer molecular weight was observed and an increase in melting point and crystallinity reported. Similarly, irradiation had a significant effect on mechanical properties with greatest decrease in tensile strength (68%) for fibers exposed to 40 kGy. The method of sterilization had no effect on cell response. Seeded tenocytes attached to all fibers and elongated parallel to the underlying fiber direction. The results demonstrate the importance of incorporating medical grade sterilization procedures early in the research projects time line to assist translation from bench to clinic. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Fabrication of poly(lactide‐co‐glycolide) scaffold embedded spatially with hydroxyapatite particles on pore walls for bone tissue engineering

Poly(lactide‐co‐glycolide) (PLGA) scaffolds embedded spatially with hydroxyapatite (HA) particles on the pore walls (PLGA/HA‐S) were fabricated by using HA‐coated paraffin spheres as porogens, which were prepared by Pickering emulsion. For comparisons, PLGA scaffolds loaded with same amount of HA particles (2%) in the matrix (PLGA/HA‐M) and pure PLGA scaffolds were prepared by using pure paraffin spheres as porogens. Although the three types of scaffolds had same pore size (450–600 µm) and similar porosity (90%–93%), the PLGA/HA‐S showed the highest compression modulus. The embedment of the HA particles on the pore walls endow the PLGA/HA‐S scaffold with a stronger ability of protein adsorption and mineralization as well as a larger mechanical strength against compression. In vitro culture of rat bone marrow stem cells revealed that cell morphology and proliferation ability were similar on all the scaffolds. However, the alkaline phosphatase activity was significantly improved for the cells cultured on the PLGA/HA‐S scaffolds. Therefore, the method for fabricating scaffolds with spatially embedded nanoparticles provides a new way to obtain the bioactive scaffolds for tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.     

Deformation behavior of electrospun poly(L‐lactide‐co‐ε‐caprolactone) nonwoven membranes under uniaxial tensile loading

Biodegradable poly(L ‐lactide‐co‐ε‐caprolactone) copolymers with different L ‐lactide (LLA)/ε‐caprolactone (CL) ratios of 75/25 and 50/50 were electrospun into fine fibers. The deformation behavior of the electrospun membranes with randomly oriented structures was evaluated under uniaxial tensile loading. The electrospun membrane with a higher LLA content showed a significantly higher tensile modulus but a similar maximum stress and a lower ultimate strain in comparison with the membrane with a lower LLA content. The beaded fibers that formed in the membranes caused lower tensile properties. X‐ray diffraction and differential scanning calorimetry results suggested that the electrospun fine fibers developed highly oriented structures in CL‐unit sequences during the electrospinning process even though the concentration was only 25 wt %. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3205–3212, 2005     

Poly(ϵ‐caprolactone‐b‐glycolide) and poly(D,L‐lactide‐b‐glycolide) diblock copolyesters: Controlled synthesis,characterization, and colloidal dispersions

Living ω‐aluminum alkoxide poly‐ϵ‐caprolactone and poly‐D,L ‐lactide chains were synthesized by the ring‐opening polymerization of ϵ‐caprolactone (ϵ‐CL) and D,L ‐lactide (D,L ‐LA), respectively, and were used as macroinitiators for glycolide (GA) polymerization in tetrahydrofuran at 40 °C. The P(CL‐b‐GA) and P(LA‐b‐GA) diblock copolymers that formed were fractionated by the use of a selective solvent for each block and were characterized by ¹H NMR spectroscopy and differential scanning calorimetry analysis. The livingness of the operative coordination–insertion mechanism is responsible for the control of the copolyester composition, the length of the blocks, and, ultimately, the thermal behavior. Because of the inherent insolubility of the polyglycolide blocks, microphase separation occurs during the course of the sequential polymerization, resulting in a stable, colloidal, nonaqueous copolymer dispersion, as confirmed by photon correlation spectroscopy. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 294–306, 2001     

Semiconductive bionanocomposites of poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) and MWCNTs for neural growth applications

Bionanocomposites of poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (P3HB3HHx) (13 % by mol of HHx) with multiwalled carbon nanotubes (MWCNTs) were prepared to obtain semiconductive nanocomposites for potential applications as scaffolds for nerve repair. The effect of the polymer/nanotube interface on the composite properties was studied using oxidized (oxi‐MWCNTs) and surface modified MWCNTs with low‐molecular weight P3HB3HHx (pol‐MWCNTs), in a ratio from 0.3 to 1.2 wt % for each type of MWCNTs employed. Morphology and conductive properties of the composites indicated a good interaction between pol‐MWCNTs and the polymer matrix. Composites with improved conductivity were obtained with only 0.3 wt % of pol‐MWCNTs added. However, agglomeration and lower conductivity was observed for samples with oxi‐MWCNTs. Cell viability studies carried out with neurospheres showed that samples with 1.2 wt % of pol‐MWCNTs are not cytotoxic and, in addition favors the neurospheres growth on the composite surface. Considering the electrical properties and biological behavior, nanocomposites of P3HB3HHx and pol‐MWCNTs are promising substrates for the regeneration of nerve tissue. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 349–360     

Nanofibrosis of uncrystallizable poly(lactide‐co‐glycolide) via phase separation

Poly(lactide‐co‐glycolide) (PLGA) copolymers are a kind of biocompatible and biodegradable materials being widely used in tissue engineering. However, phase separation had not been reported successfully in fabricating these amorphous polymers into nanofibrous matrix, although this technique had shown advantages over electrospinning in producing a nanofiber network. In this study, tetrahydrofuran (THF)/H₂O solvent pairs were found suitable solvents to induce the formation of uniform PLGA gel at selected gelation temperatures. The results indicated that fine nanofibrous structures with fiber diameter around 40–60 nm could be obtained following the steps of gel formation, solvent extraction, and freeze‐drying, by controlling the concentration of PLGA/THF/H₂O solution, THF/H₂O ratio, and gelation temperature. Copyright © 2009 John Wiley & Sons, Ltd.     

Hydrolytic degradation of poly(rac‐lactide) and poly[(rac‐lactide)‐co‐glycolide] at the air–water interface

The understanding of the simultaneous transport and chain‐scission phenomena involved in the hydrolysis of bulk‐degrading polymers requires the experimental separation of chain cleavage and water diffusion. The hydrolytic chain cleavage of poly(rac‐lactide) rac‐(PLA) and poly[(rac‐lactide)‐co‐glycolide] (PLGA) is analysed on the basis of monolayer degradation experiments combined with an improved data reduction procedure. Different, partly contradictory models of the hydrolytic degradation and erosion mechanism of PLA and PLGA, namely random chain scission and chain‐end scission, are discussed in the literature. The instantaneous linear area reduction observed for the polymer Langmuir films indicates a chain‐end scission mechanism. As monolayers of end‐capped and non‐end‐capped polymers degrade with exactly the same rate, the observed differences in the degradation kinetics of bulk samples do clearly result from differences in the water penetration into these polymers. A pronounced ‘auto‐inhibition’ effect is observed for the polymers degraded at initially high pH of the aqueous subphase in the absence of buffers. Copyright © 2007 John Wiley & Sons, Ltd.     

Novel poly(lactic acid)–poly(ethylene oxide) chain‐linked copolymer and its application in nano‐encapsulation

The work presented here investigates the synthesis of poly(lactic acid)–poly(ethylene oxide) diisocyanate chain‐linked copolymer, and its application in the nano‐encapsulation of bioactive compounds. Study was conducted on the effect of the type of chain‐linking agent, along with molecular weight, thermal properties and hydrophilic/hydrophobic behavior, through the methods of gel permeation chromatography, Fourier transform infrared spectroscopy–attenuated total reflectance, differential scanning calorimetry, light scattering, water uptake experimentation, and water contact angle measurements. Nanoparticle formation was performed via a single solvent evaporation process, and the particles obtained were characterized by dynamic light scattering and scanning electron microscopy. Results show the significantly enhanced molecular weight of the final product after the chain‐linking reaction (up to 300,000 g/mol), as well as the non‐linear nature of the sample due to broad polydispersity, ranging from 4–13. The final products exhibited glass transition temperatures of between 30 and 44 °C, while their crystalline quality was either significantly suppressed or a completely amorphous attribute was observed. Nanoparticles in the range of 300 nm that contained metazachlor were successfully prepared, and their releasing behavior exhibited first order release kinetics. A slower rate of release was observed in samples containing 4,4′‐methylenebis(phenyl isocyanate) as a chain‐linker. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and characterization of poly(vinyl alcohol)‐graft‐[poly(D,L‐lactide)/poly(D,L‐lactide‐co‐glycolide)] hydrogels

Poly(D ,L ‐lactide) and poly(D ,L ‐lactide‐co‐glycolide) with various composition and with one methacrylate and one carboxylate end group were synthesized and grafted onto poly(vinyl alcohol) (PVA) via the carboxylate group. The graft copolymers were crosslinked via the methacrylate groups using a free radical initiator. The polymer networks were characterized by means of NMR and studied qualitatively by means of IR spectroscopy. The influence of the glycolide content in the polyester grafts and of the number of ester units in the grafts on thermal properties and swellability were studied as well. The high swellability in water is characteristic of all hydrogels. Differential scanning calorimetry (DSC) showed a single glass transition temperature that occurs in the range between 51 and 69 °C. Thermogravimetric analysis (TGA) of the networks showed the main loss in weight in the temperature range between 290 and 370 °C. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4536–4544, 2007     

Molecular composites made of ionic poly(p‐phenylene terephthalamide) and poly(4‐vinylpyridine): Relaxation behavior

Molecular composites were prepared from several types of ionically modified, poly(p‐phenylene terephthalamide) (PPTA) dispersed in a poly(4‐vinylpyridine) matrix. Optical clarity tests indicated that the component polymers of the composite were miscible, at least at low concentrations of the rodlike reinforcement. In composites containing ionic PPTA, where ionic sulfonate groups were attached as side groups either to PPTA chains or to PPTA anion chains, the glass‐transition temperature (T_g) was increased by l0 °C or more, at 5 wt % reinforcement. At concentrations of 10–15 wt % of the ionic polymer, T_g values leveled off or decreased slightly. This suggested that some aggregation of the rigid‐rod molecules occurred. In composites containing ionic PPTA, where the ionic sulfonate groups were directly attached to the phenylene rings of PPTA chains, not only was T_g shifted significantly to higher temperatures, but the rubbery plateau modulus retained high values up to temperatures of 250 °C or above. Observed effects were considered to be the result of strong ionic interactions between the ionic reinforcement polymer and the polar matrix polymer. The possible effects of the counterion on T_g and the storage modulus are discussed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1110–1117, 2002     

Electrospun poly(ε‐caprolactone)‐based composites using synthesized β‐tricalcium phosphate

Non‐woven hybrid membranes based on poly(ε‐caprolactone) (PCL) and as‐synthesized β‐tricalcium phosphate (β‐TCP) were obtained by the electrospinning technique. A wide range of composition was investigated, the filler content spanning between 2 and 60 wt%. The synthesis of the β‐TCP powder was accomplished by titration of calcium hydroxide with phosphoric acid followed by calcination of the resulting precipitate at 1100°C. The as‐dried calcium phosphate was characterized by Inductive Coupled Plasma (AES‐ICP), thermal analysis (TG‐DTA), Fourier Transform Infrared Spectroscopy (FT‐IR), Scanning Electron Microscopy (SEM), and high temperature X‐ray diffraction analysis (HT‐XRD). The specific surface area (SSA) was evaluated by N₂ adsorption. Microstructure of PCL/TCP membranes was investigated by SEM, energy dispersion spectroscopy (EDS), XRD analysis, and SSA measurements. The average fiber diameter ranged between 1 and 2 µm, the porosity was 80–90%, and the SSA 16 m²/g. Mechanical properties were determined by uniaxial tensile test. A remarkable enhancement of the tensile modulus was observed for composites containing up to 4 wt% β‐TCP. The ultimate tensile strength ranged between 2 and 3 MPa for samples loaded up to 8 wt%. For most of the samples, the elongation at break was in the range 100–150%. Copyright © 2010 John Wiley & Sons, Ltd.     

Highly porous poly(lactide‐co‐glycolide) microparticles for sustained tiotropium release

In this study, porous poly(lactide‐co‐glycolide) (PLGA) microparticles with low mass density and large particle size were developed for chronic obstructive pulmonary disease treatment using anticholinergic drug (tiotropium). The porous PLGA microparticles were prepared by the water‐in‐oil‐in‐water (W₁/O/W₂) multi‐emulsion method using PLGA polymer and ammonium bicarbonate (as a porogen). Herein, soluble starch was incorporated in porous PLGA microparticles for long‐term tiotropium release. In vitro drug release studies determined that the rapid release of tiotropium from porous PLGA microparticles was reduced because of the high viscosity of the incorporated starch. Tiotropium release from porous PLGA microparticles continued up to 3 days. Furthermore, the inhaled microparticles showed longer drug residence in in vivo lung epithelium. Copyright © 2013 John Wiley & Sons, Ltd.     

Biocompatibility evaluation of self‐assembled micelles prepared from poly(lactide‐co‐glycolide)‐poly(ethylene glycol) diblock copolymers

In this work, a series of PLGA‐PEG diblock copolymers were synthesized by ring‐opening polymerization of L‐lactide and glycolide using mPEG as macroinitiator and stannous octoate as catalyst. Spherical micelles were obtained from the various copolymers by using co‐solvent evaporation method. The biocompatibility of micelles was evaluated with the aim of assessing their potential in the development of drug delivery systems. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of cytokines, hemolytic test, dynamic clotting time, protein adsorption in vitro, and zebrafish embryonic compatibility in vivo. The combined results revealed that the micelles present good cytocompatibility and hemocompatibility in vitro. Moreover, the cumulative effects of micelles throughout embryos developing stages have no toxicity in vivo. It is thus concluded that micelles prepared from PLGA‐PEG copolymers present good biocompatibility as potential drug carrier.     

A biocompatible composite based on poly(ε‐caprolactone fumarate) and hydroxyapatite

Fabrication of biodegradable composites applicable as hard tissue substitutes consisting of poly(ε‐caprolactone fumarate) (PCLF), methacrylic acid (MAA), and hydroxyapatite (HA) was investigated. PCLF macromers were synthesized by reaction of PCL diol with fumaryl chloride in the presence of propylene oxide and characterized by gel permeation chromatography, FTIR, and ¹H NMR spectroscopy. Composites were fabricated by incorporating HA as inorganic filler in PCLF matrix which followed by thermal curing of the composition using benzoyl peroxide and MAA as a free radical initiator and reactive diluent, respectively. Uniform distribution of the fine ceramic phase in the polymer matrix was elucidated by scanning electron microscopy. The effects of the initial macromer molecular weight and the filler volume fraction on mechanical properties and cytotoxicity of the composites were also examined. Significant enhancement in the mechanical properties was observed upon increasing HA content and/or initial PCLF molecular weight. The biocompatibility of the specimens was also improved with increasing ceramic phase. Copyright © 2010 John Wiley & Sons, Ltd.     

Physical properties of poly(ε‐caprolactone) layered silicate nanocomposites prepared by controlled grafting polymerization

Poly(ε‐caprolactone) (PCL) chains grafted onto montmorillonite modified by a mixture of nonfunctional ammonium salts and ammonium‐bearing hydroxyl groups were prepared. The clay content was fixed to 3 wt %, whereas the hydroxyl functionality was 25, 50, 75, and 100%, obtaining an intercalated or exfoliated system. The transport properties of water and dichloromethane vapors and the mechanical properties were investigated. The mechanical and dynamic mechanical analyses showed improvement of the nanocomposite elastic modulus in a wide temperature range. Interestingly, for the higher hydroxyl contents (50, 75, and 100%), the decrease of modulus at higher temperature, due to the PCL crystalline melting, did not lead to the loss of mechanical consistence of the samples. Consequently, they revealed a measurable modulus up to 120 °C, a much higher temperature with respect to pure PCL. Water sorption was investigated in the entire activity range, and a lower sorption was observed on increasing the hydroxyl content, up to the sample with 100% hydroxyl content, which turned to be completely impermeable, even in liquid water. The sample with 75% hydroxyl content showed a threshold activity (a = 0.4) below which it was impermeable to water vapor. Also, the diffusion parameters decreased when the hydroxyl content increased, up to the 100% sample, which showed zero diffusion. The diffusion parameters of an organic vapor, dichloromethane, also exhibited a decreasing value on increasing the hydroxyl content in the nanocomposites. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1466–1475, 2004     

Hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer and their nanoparticles as paclitaxel delivery system

A new hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer (HPAE‐co‐PLGA) was synthesized by ring‐opening polymerization of D , L ‐lactide (DLLA) glycolid and branched poly (amine‐ester) (HPAE‐OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT‐IR, ¹H‐NMR(¹³C NMR), TGA and their molecular weights were determined by gel permeation chromatography (GPC). Paclitaxel‐loaded copolymer nanoparticles were prepared by the nanoprecipitation method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). Paclitaxel‐loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug‐loading content, and drug release behavior. As the molar ratio of DL ‐lactide/glycolide to HPAE increased, the nanoparticles size and drug‐loading content increased, and the drug release rate decreased. The antitumor activity of the paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles against human liver cancer H7402 cells was evaluated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles showed comparable anticancer efficacy with the free drug. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and characterization of novel biodegradable block copolymer poly(ethylene glycol)‐block‐poly(L‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylene carbonate)

An amphiphilic block copolymer, poly(ethylene glycol)‐block‐poly(L ‐lactide‐co‐2‐methyl‐2‐benzoxycarbonyl‐propylene carbonate) [PEG‐b‐P(LA‐co‐MBC)], was synthesized in bulk by the ring‐opening polymerization of L ‐lactide with 2‐methyl‐2‐benzoxycarbonyl‐propylene carbonate (MBC) in the presence of poly(ethylene glycol) as a macroinitiator with diethyl zinc as a catalyst. The subsequent catalytic hydrogenation of PEG‐b‐P(LA‐co‐MBC) with palladium hydroxide on activated charcoal (20%) as a catalyst was carried out to obtain the corresponding linear copolymer poly(ethyleneglycol)‐block‐poly(L ‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylenecarbonate) [PEG‐b‐P(LA‐co‐MCC)] with pendant carboxyl groups. DSC analysis indicated that the glass‐transition temperature (T_g) of PEG‐b‐P(LA‐co‐MBC) decreased with increasing MBC content in the copolymer, and T_g of PEG‐b‐P(LA‐co‐MCC) was higher than that of the corresponding PEG‐b‐P(LA‐co‐MBC). The in vitro degradation rate of PEG‐b‐P(LA‐co‐MCC) in the presence of proteinase K was faster than that of PEG‐b‐P(LA‐co‐MBC), and the cytotoxicity of PEG‐b‐P(LA‐co‐MCC) to chondrocytes from human fetal arthrosis was lower than that of poly(L ‐lactide). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4771–4780, 2005     

Phase behavior of modified montmorillonite– poly(ϵ‐caprolactone) nanocomposites

The thermal behavior and overall isothermal crystallization kinetics of a series of organophilic modified montmorillonite–poly(?‐caprolactone) nanocomposites were investigated. In general, the thermal behavior was influenced more by the type of dispersion than by the clay content. For nanocomposites in which silicate platelets were predominantly dispersed in the polymer matrix to give exfoliated structures, the thermal properties were improved with respect to those of neat poly(?‐caprolactone), whereas in those cases in which simply intercalated structures were attained, the thermal properties regularly decayed as the clay content increased. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1321–1332, 2004