Renewable-resource thermoplastic elastomers based on polylactide and polymenthide

An alpha,omega-functionalized polymenthide was synthesized by the ring-opening polymerization of menthide in the presence of diethylene glycol with diethyl zinc as the catalyst. Termination with water afforded the dihydroxy polymenthide. The reaction of this telechelic polymer with triethylaluminum formed the corresponding aluminum alkoxide macroinitiator that was used for the controlled polymerization of lactide to yield biorenewable polylactide-b-polymenthide-b-polylactide triblock copolymers. The molecular weight and chemical composition were easily adjusted by the monomer-to-initiator ratios. Microphase separation in these triblock copolymers was confirmed by small-angle X-ray scattering and differential scanning calorimetry. A representative triblock was prepared with a hexagonally packed cylindrical morphology as determined by small-angle X-ray scattering, and tensile testing was employed to assess the mechanical behavior. On the basis of the ultimate elongations and elastic recovery, these triblock copolymers behaved as thermoplastic elastomers.     

Resorbable and highly elastic block copolymers from 1,5-dioxepan-2-one and L-lactide with controlled tensile properties and hydrophilicity

New resorbable and elastomeric ABA tri- and multiblock copolymers have been successfully synthesized by combining ring-opening polymerization with ring-opening polycondensation. Five different poly(L-lactide-b-1,5-dioxepan-2-one-b-L-lactide) triblock copolymers and one new poly(L-lactide-b-1,5-dioxepan-2-one) multiblock copolymer have been synthesized. The triblock copolymers were obtained by ring-opening polymerization of 1,5-dioxepan-2-one (DXO) and L-lactide (LLA) with a cyclic tin initiator. The new multiblock copolymer was prepared by ring-opening polycondensation of a low molecular weight triblock copolymer with succinyl chloride. The molecular weight and the composition of the final copolymers were easily controlled by adjusting the monomer feed ratio, and all of the polymers obtained had a narrow molecular weight distribution. It was possible to tailor the hydrophilicity of the materials by changing the DXO content. Copolymers with a high DXO content had a more hydrophilic surface than those with a low DXO content. The receding contact angle varied from 27 to 44 degrees. The tensile properties of the copolymers were controlled by altering the PDXO block length. The tensile testing showed that all the polymers were very elastic and had very high elongations-at-break (epsilon(b)). The copolymers retained very good mechanical properties (epsilon(b) approximately 600-800% and sigma(b) approximately 8-20 MPa) throughout the in vitro degradation study (59 days).     

Self-assembled micelles of biodegradable triblock copolymers based on poly(ethyl ethylene phosphate) and poly(-caprolactone) as drug carriers

A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL block lengths were synthesized and characterized. These triblock copolymers formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution. The micelle morphology was spherical, determined by transmission electron microscopy. It was found that the size and critical micelle concentration values of the micelles depended on both hydrophobic PCL block length and PEEP hydrophilic block length. The in vitro degradation characteristics of the triblock copolymers were investigated in micellar form, showing that these copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas lipase and phosphodiesterase I. These triblock copolymers were used for paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX was successfully loaded into the micelles, and the in vitro release profile was found to be correlative to the polymer composition. These biodegradable triblock copolymer micelles are potential as novel carriers for hydrophobic drug delivery.     

Resilient bioresorbable copolymers based on trimethylene carbonate, L-lactide, and 1,5-dioxepan-2-one

The new combinations of monomers presented in this work were evaluated in order to create an elastic material for potential application in soft tissue engineering. Thermoplastic elastomers (TPE) of trimethylene carbonate (TMC) with L-lactide (LLA) and 1,5-dioxepan-2-one (DXO) have been synthesized using a cyclic five-membered tin alkoxide initiator. The block copolymers were designed in such a way that poly(trimethylene carbonate-co-1,5-dioxepan-2-one) formed an amorphous middle block and the poly(L-lactide) (PLLA) formed semicrystalline terminal blocks. The amorphous middle block consisted of relatively randomly distributed TMC and DXO monomer units, and the defined block structure of the PLLA terminal segments was confirmed by 13C NMR. The properties of the TMC-DXO-LLA copolymers were compared with those of triblock copolymers based either on LLA-TMC or on LLA-DXO. Differential scanning calorimetry and dynamic mechanical analysis data confirmed the micro-phase separation in the copolymers. The mechanical properties of the copolymers were evaluated using tensile testing and cycling loading. All of the copolymers synthesized showed a highly elastic behavior. The properties of copolymers could be tailored by altering the proportions of the different monomers.     

Intermolecular interaction and morphology investigation of drug loaded ABA-triblock copolymers with different hydrophilic/lipophilic ratios

Copolymers with different hydrophilic/lipophilic ratios (HLR) were used to optimize the compatibility between polymer as drug carrier and quercetin as lipophilic drug. Synthesis of amphiphilic triblock copolymers (TC) of poly(butylene adipate)–poly(ethylene glycol)–poly(butylene adipate) (PBA–PEG–PBA) with different PBA molecular weights is the first approach for this purpose. Polymerization and structural features of the polymers were analyzed by different characterization techniques (GPC, ¹H NMR and FT-IR). Formation of hydrophobic and hydrophilic domains with different ratios in the ABA-triblock copolymers was studied by ¹H NMR. The sunflower-like nanoparticles were prepared by self-assembling of the amphiphilic copolymers in the aqueous solution. The hydrophobic PBA segments formed the central solid-like core which stabilized by the hydrophilic PEG rings. The optimum HLR for these copolymers was determined on the basis of drug release time and profile, obtained from freeze-dried nanoparticle powders. The results indicated that optimum HLR for the sustained quercetin release obtained at higher molecular weight of polyesteric domains. Zeta potential measurements showed that the nanoparticle size was close related to the initial concentrations of the nanoparticle dispersions and the compositions of the triblock copolymers. Moreover, TEM pictures showed that the nanocarriers morphologies were changed by changing HLR of triblock copolymers. The PBA–PEG–PBA nanoparticles also showed good drug loading properties, suggesting that they were very suitable as delivery devices for hydrophobic drugs.     

Evaluation of Fiber Reinforced Cement Using Digital Image Correlation

The effect of short fiber reinforcements on the mechanical properties of cement has been examined using a splitting tensile – digital image correlation (DIC) measurement method. Three short fiber reinforcement materials have been used in this study: fiberglass, nylon, and polypropylene. The method outlined provides a simple experimental setup that can be used to evaluate the ultimate tensile strength of brittle materials as well as measure the full field strain across the surface of the splitting tensile test cylindrical specimen. Since the DIC measurement technique is a contact free measurement this method can be used to assess sample failure.     

Degradation behavior of poly(epsilon-caprolactone)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles in aqueous solution

Poly(epsilon-caprolactone)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone) triblock copolymers were synthesized by the ring-opening polymerization of epsilon-caprolactone in the presence of hydroxyl-terminated poly(ethylene glycol) with different molecular weights, using stannous octoate catalyst. Micelles prepared by the precipitation method with these triblock copolymers exhibit a core-shell structure. The degradation behaviors of these core-shell micelles in aqueous solution were investigated by FT-IR, 1H NMR, GPC, DLS, TEM, and AFM. It was found that the degradation behavior of micelles in aqueous solution was quite different from that of bulk materials. The size of the micelles increased in the initial degradation stages and decreased gradually when the degradation period was extended. The caprolactone/ethylene oxide (CL/EO) ratio in micelles measured by NMR also shows an increase at the initial degradation stage and a decrease at later stages. The morphology of these micelles became more and more irregular during the degradation period. We explain the observed behavior by a two-stage degradation mechanism with interfacial erosion between the cores and the shells followed by core erosion.     

Effect of adhesive on the morphology and mechanical properties of electrospun fibrous mat of cellulose acetate

Ultrafine fibers of cellulose acetate/poly(butyl acrylate) (CA/PBA) composite in which PBA acted as an adhesive and CA acted as a matrix, were successfully prepared as fibrous mat via electrospinning. The morphology observation from the electrospun CA/PBA composite fibers, after treatment with heat hardener, revealed that the fibers were cylindrical and had point-bonded structures. SEM, FT-IR spectra, Raman spectra, TGA analysis, and mechanical properties measurement were used to study the different properties of hybrid mats. The tensile strength of blend fibrous electrospun mats was found to be effectively increased. This resultant enhancement of the mechanical properties of polymer fibrous mats, caused by generating the point-bonded structures (due to adhesive), could increase the number of potential applications of mechanically weak electrospun CA fibers.     

Macromolecular design of aliphatic polyesters with maintained mechanical properties and a rapid, customized degradation profile

An innovative type of triblock copolymer that maintains and even increases the mechanical properties of poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL) with a controlled, predictable, and rapid degradation profile has been synthesized. Elastic triblock copolymers were formed from the hydrophobic and crystalline PLLA and PCL with an amorphous and hydrophilic middle block of poly(but-2-ene-1,4-diyl malonate) (PBM). The polymers were subjected to degradation in PBS at 37 °C for up to 91 days. Prior to degradation, ductility of the PLLA-PBM-PLLA was approximately 4 times greater than that of the homopolymer of PLLA, whereas the modulus and tensile stress at break were unchanged. A rapid initial hydrolysis in the amorphous PBM middle block changed the microstructure from triblock to diblock with a significant reduction in ductility and molecular weight. The macromolecular structure of the triblock copolymer of PLLA and PBM generates a more flexible and easier material to handle during implant, with the advantage of a customized degradation profile, demonstrating its potential use in future biomedical applications.     

Structure and properties of two plastic peptide triblock,ABA, copolymers of poly(γ-benzyl-l-glutamate), A,and poly(butadiene/acrylonitrile), B

Two prototype triblock (ABA) copolymers of poly[(γ-benzyl-l-glutamate) _x (butadiene/acrylonitrile)_y (γ-benzyl-l-glutamate)_x] have been synthesized and characterized. They were prepared by reacting a primary amine capped butadiene/acrylonitrile (ATBN) polymer with the $\text{N-}\text{carboxy}$ anhydride of γ-benzyl-l-glutamate. The copolymers were ～38 000 (copolymer 1) and 74 000 (copolymer II) molecular weight. X-ray diffraction and Fourier Transform infrared spectroscopy of films cast from dioxane (preferential for PBLG) and chloroform (non-preferential) show the benzyl glutamate segments to be predominantly α-helical and disordered α-helical, respectively. Electron microscopy of osmium tetroxide strained films cast from dioxane revealed lamellar domain formation indicative of phase separation. The midblock butadiene layers were ～150 Å thick while the alternating benzyl glutamate layers were 300 and 500 Å thick for copolymers I and II, respectively. Films cast from chloroform exhibit a nearly homogeneous morphology, indicative of considerable phase mixing. Dynamic mechanical spectroscopy of the copolymers also revealed a dependence on morphology. The side chain transition of the benzyl glutamate appeared as a single peak when the copolymers were cast from dioxane and a double peak when the copolymers were cast from chloroform.     

Reversible hydrogels from self-assembling genetically engineered protein block copolymers

A series of triblock protein copolymers composed of a central water-soluble polyelectrolyte segment flanked by two coiled-coil domains was synthesized by genetic engineering methods. The copolymers self-assembled into reversible hydrogels in response to changes in temperature, pH, and the presence or absence of denaturating agent (guanidine hydrochloride, GdnHCl). Hydrogel formation was concentration-dependent, and the concentration needed for hydrogel formation correlated with the oligomerization state of the coiled-coil domains in the protein copolymers. The morphology of the hydrogels, as determined by scanning electron microscopy (SEM), indicated the presence of porous interconnected networks. The thermal stabilities and self-assembling properties of the protein copolymers were successfully controlled by manipulating the amino acid sequences of the coiled-coil domains. The stimuli responsiveness and reversibility of the hydrogel self-assembly suggest that these protein copolymers may have potential in biomedical applications.     

Synthesis and characterization of glycopolymer-polypeptide triblock copolymers

Glycopolymer-polypeptide triblock copolymers of the structure, poly(l-alanine)-b-poly(2-acryloyloxyethyl-lactoside)-b-poly(l-alanine) (AGA), have been synthesized by sequential atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP). Controlled free radical polymerization of 2-O-acryloyl-oxyethoxyl-(2,3,4,6-tetra-O-acetyl-beta-d-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-beta-d-glucopyranoside (AEL) by ATRP with a dibromoxylene (DBX)/CuBr/bipy complex system was used to generate a central glycopolymer block. Telechelic glycopolymers with diamino end groups were obtained by end group transformation and subsequently used as macroinitiators for ROP of l-alanine N-carboxyanhydride monomers (Ala-NCA). Gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy analysis demonstrated that copolymer molecular weight and composition were controlled by both the molar ratios of the Ala-NCA monomer to macroinitiator and monomer conversion and exhibited a narrow distribution (Mw/Mn = 1.06-1.26). FT-IR spectroscopy of triblock copolymers revealed that the ratio of alpha-helix/beta-sheet increased with poly(l-alanine) block length. Of note, transmission electron microscopy (TEM) demonstrated that selected amphiphilic glycopolymer-polypeptide triblock copolymers self-assemble in aqueous solution to form nearly spherical aggregates of several hundreds nanometer in diameter. Significantly, the sequential application of ATRP and ROP techniques provides an effective method for producing triblock copolymers with a central glycopolymer block and flanking polypeptide blocks of defined architecture, controlled molecular weight, and low polydispersity.     

Controlled delivery of paclitaxel from stent coatings using poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene) and its acetylated derivative

A poly(styrene-b-isobutylene-b-styrene) (SIBS) triblock polymer is employed as the polymer drug carrier for the TAXUS Express2 Paclitaxel-Eluting Coronary Stent system (Boston Scientific Corp.). It has been shown that the release of paclitaxel (PTx) from SIBS can be modulated by modification of either drug-loading ratio or altering the triblock morphology by blending. In the present work, results toward achieving release modulation of PTx by chemical modification of the styrenic portion (using hydroxystyrene or its acetylated version) of the SIBS polymer system are reported. The synthesis of the precursor poly[(p-tert-butyldimethylsilyloxystyrene)]-b-isobutylene-b-[(p-tert-butyldimethylsilyloxystyrene] triblock copolymers was accomplished by living sequential block copolymerization of isobutylene (IB) and p-(tert-butyldimethylsiloxy)styrene (TBDMS) utilizing the capping-tuning technique in a one-pot procedure in methylcyclohexane/CH3Cl at -80 degrees C. This procedure involved the living cationic polymerization of IB with the 5-tert-butyl-1,3-bis(1-chloro-1-methylethyl)benzene/TiCl4 initiating system and capping of living difunctional polyisobutylene (PIB) chain ends with 1,1-ditolylethylene (DTE) followed by addition of titanium(IV) isopropoxide (Ti(OIp)4) to lower the Lewis acidity before the introduction of TBDMS. Deprotection of the product with tetrabutylammonium fluoride yielded poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene), which was quantitatively acetylated to obtain the acetylated derivative. The hydroxystyrene and acetoxystyrene triblock copolymers have acceptable mechanical properties for use as drug delivery coatings for coronary stent applications. It was concluded that the hydrophilic nature of the endblocks and polarity effects on the drug/polymer miscibility lead to enhanced release of PTx from these polymers. The drug-polymer miscibility was confirmed by differential scanning calorimetry and atomic force microscopy evaluations.     

Multiblock copolymers of L-lactide and trimethylene carbonate

Sequential copolymerizations of trimethylene carbonate (TMC) and l-lactide (LLA) were performed with 2,2-dibutyl-2-stanna-1,3-oxepane as a bifunctional cyclic initiator. The block lengths were varied via the monomer/initiator and via the TMC/l-lactide ratio. The cyclic triblock copolymers were transformed in situ into multiblock copolymers by ring-opening polycondensation with sebacoyl chloride. The chemical compositions of the block copolymers were determined from (1)H NMR spectra. The formation of multiblock structures and the absence of transesterification were proven by (13)C NMR spectroscopy. Differential scanning calorimetry (DSC), wide-angle X-ray scattering (WAXS), and dynamic mechanical analysis (DMA) measurements confirmed the existence of a microphase-separated structure in the multiblock copolymers consisting of a crystalline phase of poly(LLA) blocks and an amorphous phase formed by the poly(TMC) blocks. Stress-strain measurements showed the elastomeric character of these biodegradable multiblock copolymers, particularly in copolymers having epsilon-caprolactone as comonomer in the poly(TMC) blocks.     

Thermoreversible hydrogels from RAFT-synthesized BAB triblock copolymers: steps toward biomimetic matrices for tissue regeneration

Narrowly dispersed, temperature-responsive BAB block copolymers capable of forming physical gels under physiological conditions were synthesized via aqueous reversible addition fragmentation chain transfer (RAFT) polymerization. The use of a difunctional trithiocarbonate facilitates the two-step synthesis of BAB copolymers with symmetrical outer blocks. The outer B blocks of the triblock copolymers consist of poly(N-isopropylacrylamide) (PNIPAM) and the inner A block consists of poly(N,N-dimethylacrylamide). The copolymers form reversible physical gels above the phase transition temperature of PNIPAM at concentrations as low as 7.5 wt % copolymer. Mechanical properties similar to collagen, a naturally occurring polypeptide used as a three-dimensional in vitro cell growth scaffold, have been achieved. Herein, we report the mechanical properties of the gels as a function of solvent, polymer concentration, and inner block length. Structural information about the gels was obtained through pulsed field gradient NMR experiments and confocal microscopy.     

De novo synthesis and cellular uptake of organic nanocapsules with tunable surface chemistry

Water-soluble organic nanocapsules were prepared from bottlebrush copolymers with triblock terpolymer side chains composed of a degradable inner block (polylactide), a cross-linkable middle block (poly(4-butenylstyrene)), and a functional outer block (poly(styrene-co-maleic anhydride)). Bottlebrush copolymers are macromolecules with a long linear backbone and shorter polymeric side chains densely grafted onto the backbone. Hollow cylindrical nanoparticles were prepared by peripheral cross-linking of the bottlebrush copolymers and subsequent selective removal of the core. Reactive anhydride groups of the outer functional layer allowed for the preparation of nanocapsules with tunable surface characteristics. Cellular uptake of negatively charged organic nanocapsules showed strong surface chemistry dependence. The presence of hydrophobic groups on the nanocapsule surface was necessary for their nonspecific association with the cell membrane and subsequent internalization by endocytosis. The length of surface grafted oligoethylene glycol chains also had a dramatic influence on the intracellular accumulation of nanocapsules. Macropinocytosis was shown to be the predominant pathway for the cellular uptake of organic nanocapsules.     

Preparation and mechanical properties of chitosan/carbon nanotubes composites

Biopolymer chitosan/multiwalled carbon nanotubes (MWNTs) nanocomposites have been successfully prepared by a simple solution-evaporation method. The morphology and mechanical properties of the chitosan/MWNTs nanocomposites have been characterized with field emission scanning electron microscopy (SEM), bright field transmission electron microscopy (TEM), optical microscopy (OM), wide-angle X-ray diffraction (XRD), and tensile as well as nanoindentation tests. The MWNTs were observed to be homogeneously dispersed throughout the chitosan matrix. When compared with neat chitosan, the mechanical properties, including the tensile modulus and strength, of the nanocomposites are greatly improved by about 93% and 99%, respectively, with incorporation of only 0.8 wt % of MWNTs into the chitosan matrix.     

Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b-polyethylenimine triblock copolymers: synthesis, characterization, and in vitro gene transfer properties

Novel ABA triblock copolymers consisting of low molecular weight linear polyethylenimine (PEI) as the A block and poly(ethylene glycol) (PEG) as the B block were prepared and evaluated as polymeric transfectant. The cationic polymerization of 2-methyl-2-oxazoline (MeOZO) using PEG-bis(tosylate) as a macroinitiator followed by acid hydrolysis afforded linear PEI-PEG-PEI triblock copolymers with controlled compositions. Two copolymers, PEI-PEG-PEI 2100-3400-2100 and 4000-3400-4000, were synthesized. Both copolymers were shown to interact with and condense plasmid DNA effectively to give polymer/DNA complexes (polyplexes) of small sizes (<100 nm) and moderate zeta-potentials (approximately +10 mV) at polymer/plasmid weight ratios > or =1.5/1. These polyplexes were able to efficiently transfect COS-7 cells and primary bovine endothelial cells (BAECs) in vitro. For example, PEI-PEG-PEI 4000-3400-4000 based polyplexes showed a transfection efficiency comparable to polyplexes of branched PEI 25000. The transfection activity of polyplexes of PEI-PEG-PEI 4000-3400-4000 in BAECs using luciferase as a reporter gene was 3-fold higher than that for linear PEI 25000/DNA formulations. Importantly, the presence of serum in the transfection medium had no inhibitive effect on the transfection activity of the PEI-PEG-PEI polyplexes. These PEI-PEG-PEI triblock copolymers displayed also an improved safety profile in comparison with high molecular weight PEIs, since the cytotoxicity of the polyplex formulations was very low under conditions where high transgene expression was found. Therefore, linear PEI-PEG-PEI triblock copolymers are an attractive novel class of nonviral gene delivery systems.     

Deformation responses of a physically cross-linked high molecular weight elastin-like protein polymer

Recombinant protein polymers were synthesized and examined under various loading conditions to assess the mechanical stability and deformation responses of physically cross-linked, hydrated, protein polymer networks designed as triblock copolymers with central elastomeric and flanking plastic-like blocks. Uniaxial stress-strain properties, creep and stress relaxation behavior, as well as the effect of various mechanical preconditioning protocols on these responses were characterized. Significantly, we demonstrate for the first time that ABA triblock protein copolymers when redesigned with substantially larger endblock segments can withstand significantly greater loads. Furthermore, the presence of three distinct phases of deformation behavior was revealed upon subjecting physically cross-linked protein networks to step and cyclic loading protocols in which the magnitude of the imposed stress was incrementally increased over time. We speculate that these phases correspond to the stretch of polypeptide bonds, the conformational changes of polypeptide chains, and the disruption of physical cross-links. The capacity to select a genetically engineered protein polymer that is suitable for its intended application requires an appreciation of its viscoelastic characteristics and the capacity of both molecular structure and conditioning protocols to influence these properties.     

In vivo characterization of mechanical tissue properties of internal organs using endoscopic microscopy and inverse finite element analysis

Knowledge about mechanical tissue properties is required for functional modelling and simulating of tissue and organ responses to external mechanical stress. To get the right properties especially for functional modelling of organs, tissue properties have to be determined in vivo. There are only few described methods for characterization of internal organ's tissue mechanics that can be applied in vivo. We introduce and evaluate a method to determine mechanical tissue properties, especially those of lung tissue, endoscopically. Inverse finite element analysis (utilizing a Neo-Hookean model for hyperelastic materials) and image processing algorithms are used to determine the shear modulus of a soft tissue. The resulting values for shear moduli were normally distributed. The shear modulus of the artificial tissue sample was determined with a relative error of 0.47% compared to the value obtained by uniaxial tensile test.