Random cationic copolymer brushes composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and N-isopropylacrylamide (NIPAAm) were synthesized using the atom transfer radical polymerization (ATRP) method. The effects of varying the monomer feed ratios (30:70 and 70:30 DMAEMA:NIPAAm) and polymerization times on the film height, morphology and stimuli response to pH of the brush were evaluated. While the polymerization time was found to have little influence on the properties of the brushes, the monomer feed ratios had a great impact. The 70 % DMAEMA polymer brush had similar height as the 30 % DMAEMA brush after 45 min; however, it had a greater response to pH and morphological change compared to the 30 % DMAEMA. The 70 % DMAEMA brush was used to demonstrate an efficient approach to alleviate the ion suppression effect in MALDI analysis of complex mixtures by effectively fractionating a binary mixture of peptides prior to MALDI-MS analysis.
Polymer Brush; Peptide Fractionation; Stimuli Response
The objective of this work was to investigate the effect of chemical composition and segment number (n) on gelation, stiffness, and degradation of hydroxy acid-chain-extended star polyethylene glycol acrylate (SPEXA) gels. The hydroxy acids included glycolide (G,), L-lactide (L), p-dioxanone (D) and -caprolactone (C). Chain-extension generated water soluble macromers with faster gelation rates, lower sol fractions, higher compressive moduli, and a wide-ranging degradation times when crosslinked into a hydrogel. SPEGA gels with the highest fraction of inter-molecular crosslinks had the most increase in compressive modulus with n whereas SPELA and SPECA had the lowest increase in modulus. SPEXA gels exhibited a wide range of degradation times from a few days for SPEGA to a few weeks for SPELA, a few months for SPEDA, and many months for SPECA. Marrow stromal cells and endothelial progenitor cells had the highest expression of vasculogenic markers when co-encapsulated in the faster degrading SPELA gel.
hydrogel chain extension; hydroxy acids; cell encapsulation
This study reports a facile method for the fabrication of aligned Poly(3,4-ethylene dioxythiophene) (PEDOT) fibers and tubes based on electrospinning and oxidative chemical polymerization. Discrete PEDOT nano- and microfibers and nano- and microtubes are difficult to fabricate quickly and reproducibly. We employed poly(lactide-co-glycolide) (PLGA) polymers that were loaded with polymerizable 3,4-ethylene dioxythiophene (EDOT) monomer to create aligned nanofiber assemblies using a rotating glass mandrel during electrospinning. The EDOT monomer/PLGA polymer blends were then polymerized by exposure to an oxidative catalyst (FeCl3). PEDOT was polymerized by continuously dripping a FeCl3 solution onto the glass rod during electrospinning. The resulting PEDOT fibers were conductive, aligned and discrete. Fiber bundles could be easily produced in lengths of several centimeters. The PEDOT sheath/PLGA core fibers were immersed in chloroform to remove the PLGA and any residual EDOT resulting in hollow PEDOT tubes. This approach made it possible to easily generate large areas of aligned PEDOT fibers/tubes. The structure and properties of the aligned assemblies were measured using optical microscopy, electron microscopy, Raman spectroscopy, thermal gravimetric analysis, and DC conductivity measurements. We also demonstrated that the aligned PEDOT sheath/PLGA core fiber assemblies could be used in supporting and directing the extension of dorsal root ganglia (DRG) neurons in vitro.
The thermo-responsive behavior of a unique biocompatible polymer, poly(N-substituted α/β-asparagine) derivative (PAD), has been studied with several NMR methods. The 1H and 13C solution NMR measurements of the PAD in DMSO-d6 were used to investigate the isolated polymer and perform spectral assignments. By systematic addition of D2O we have tracked structural changes due to aggregation and observed contraction of hydrophilic side chains. Solution and cross polarization / magic angle spinning (CP/MAS) 13C NMR approaches were implemented to investigate the aggregates of the PAD aqueous solution during the liquid to gel transition as the temperature was increased. At temperatures near 20 °C, all of the peaks from the PAD were observed in the 13C CP/MAS and 13C solution NMR spectra, indicating the presence of polymer chain nodes. Increasing the temperature to 40 °C resulted in a partial disentanglement of the nodes due to thermal agitation and further heating resulted in little to no additional structural changes. Deuterium T1–T2 and T2–T2 two-dimensional relaxation spectroscopies using an inverse Laplace transform, were also implemented to monitor the water–PAD interaction during the phase transition. At temperatures near 20 °C the dynamical characteristics of water were manifested into one peak in the deuterium T1–T2 map. Increasing the temperature to 40 °C resulted in several distinguishable reservoirs of water with different dynamical characteristics. The observation of several reservoirs of water at the temperature of gel formation at 40 °C is consistent with a physical picture of a gel involving a network of interconnected polymer chains trapping a fluid. Further increase in temperature to 70 °C resulted in two non-exchanging water reservoirs probed by deuterium T2–T2 measurements.
Cell patches are widely used for healing injuries on the surfaces or interfaces of tissues such as those of epidermis and myocardium. Here we report a novel type of porous scaffolds made of poly(D,L-lactic-co-glycolic acid) for fabricating cell patches. The scaffolds have a single layer of spherical pores arranged in a unique hexagonal pattern and are therefore referred to as “scaffolds with a hexagonal array of interconnected pores (SHAIPs)”. SHAIPs contain both uniform pores and interconnecting windows that can facilitate the exchange of biomacromolecules, ensure homogeneous cell seeding, and promote cell migration. As a proof-of-concept demonstration, we have created skeletal muscle patches with a thickness of approximately 150 μm using SHAIPs. The myoblasts seeded in the scaffolds maintained high viability and were able to differentiate into multi-nucleated myotubes. Moreover, neovasculature could efficiently develop into the patches upon subcutaneous implantation in vivo.
porous scaffolds; cell patches; C2C12 myoblasts; photoacoustic microscopy; tissue engineering; regenerative medicine
Injury caused by trauma, burns, surgery, or disease often results in soft tissue loss leading to impaired function and permanent disfiguration. Tissue engineering aims to overcome the lack of viable donor tissue by fabricating synthetic scaffolds with the requisite properties and bioactive cues to regenerate these tissues. Biomaterial scaffolds designed to match soft tissue modulus and strength should also retain the elastomeric and fatigue-resistant properties of the tissue. Of particular design importance is the interconnected porous structure of the scaffold needed to support tissue growth by facilitating mass transport. Adequate mass transport is especially true for newly implanted scaffolds that lack vasculature to provide nutrient flux. Common scaffold fabrication strategies often utilize toxic solvents and high temperatures or pressures to achieve the desired porosity. In this study, a polymerized medium internal phase emulsion (polyMIPE) is used to generate an injectable graft that cures to a porous foam at body temperature without toxic solvents. These poly(ester urethane urea) scaffolds possess elastomeric properties with tunable compressive moduli (20–200 kPa) and strengths (4–60 kPa) as well as high recovery after the first conditioning cycle (97–99%). The resultant pore architecture was highly interconnected with large voids (0.5–2 mm) from carbon dioxide generation surrounded by water-templated pores (50–300 μm). The ability to modulate both scaffold pore architecture and mechanical properties by altering emulsion chemistry was demonstrated. Permeability and form factor were experimentally measured to determine the effects of polyMIPE composition on pore interconnectivity. Finally, initial human mesenchymal stem cell (hMSC) cytocompatibility testing supported the use of these candidate scaffolds in regenerative applications. Overall, these injectable polyMIPE foams show strong promise as a biomaterial scaffold for soft tissue repair.
Although methods have been developed to synthesize and isolate generation 5 (G5) PAMAM dendrimers containing precise numbers of ligands per polymer particle, the presence of skeletal and generational defects in this material can substantially hamper the process. Here we provide a quantitative analysis of G5 PAMAM dendrimer defects via high performance liquid chromatography, potentiometric titration, mass spectrometry, size exclusion chromatography, and nuclear magnetic resonance. We identified, isolated, and characterized the major structural defects of G5 dendrimer, trailing generations, and dimer, trimer, and tetramer species. We determine that the G5 material present in the as-received mixture contains 93 arms on average. We have developed two model systems capable of generating the experimentally observed mass range and polydispersity at defect rates of 8–15%.
PAMAM dendrimer; HPLC; Mass spectrometry
The objectives of this work were: (1) to select suitable compositions of tyrosine-derived polycarbonates for controlled delivery of voclosporin, a potent drug candidate to treat ocular diseases, (2) to establish a structure-function relationship between key molecular characteristics of biodegradable polymer matrices and drug release kinetics, and (3) to identify factors contributing in the rate of drug release. For the first time, the experimental study of polymeric drug release was accompanied by a hierarchical sequence of three computational methods. First, suitable polymer compositions used in subsequent neural network modeling were determined by means of response surface methodology (RSM). Second, accurate artificial neural network (ANN) models were built to predict drug release profiles for fifteen polymers located outside the initial design space. Finally, thermodynamic properties and hydrogen-bonding patterns of model drug-polymer complexes were studied using molecular dynamics (MD) technique to elucidate a role of specific interactions in drug release mechanism. This research presents further development of methodological approaches to meet challenges in the design of polymeric drug delivery systems.
hydrophobic peptide; polymeric drug release; structure-function relationship; computational modeling; hydrogen bonding
Photodegradable hydrogels have emerged as a powerful material platform for studying and directing cell behaviors, as well as for delivering drugs. The premise of this technique is to use a cytocompatible light source to cleave linkers within a hydrogel, thus causing reduction of matrix stiffness or liberation of matrix-tethered biomolecules in a spatial-temporally controlled manner. The most commonly used photodegradable units are molecules containing nitrobenzyl moieties that absorb light in the ultraviolet (UV) to lower visible wavelengths (~280 to 450 nm). Because photodegradable linkers and hydrogels reported in the literature thus far are all sensitive to UV light, highly efficient UV-mediated photopolymerizations are less likely to be used as the method to prepare these hydrogels. As a result, currently available photodegradable hydrogels are formed by redox-mediated radical polymerizations, emulsion polymerizations, Michael-type addition reactions, or orthogonal click chemistries. Here, we report the first photodegradable poly(ethylene glycol)-based hydrogel system prepared by step-growth photopolymerization. The model photolabile peptide cross-linkers, synthesized by conventional solid phase peptide synthesis, contained terminal cysteines for step-growth thiol-ene photo-click reactions and a UV-sensitive 2-nitrophenylalanine residue in the peptide backbone for photo-cleavage. Photolysis of this peptide was achieved through adjusting UV light exposure time and intensity. Photopolymerization of photodegradable hydrogels containing photolabile peptide cross-linkers was made possible via a highly efficient visible light-mediated thiol-ene photo-click reaction using a non-cleavage type photoinitiator eosin-Y. Rapid gelation was confirmed by in situ photo-rheometry. Flood UV irradiation at controlled wavelength and intensity was used to demonstrate the photodegradability of these photopolymerized hydrogels.
Photopolymerization; photodegradable hydrogels; thiol-ene; click reaction
The field of bone and cartilage tissue engineering has a pressing need for novel, biocompatible, biodegradable biocomposites comprising polymers with bioceramics or bioglasses to meet numerous requirements for these applications. We created hydrolytically degradable hydrogel/bioceramic biocomposites, comprising poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels and 50 wt% biphasic hydroxyapatite/β-tricalcium phosphate (60/40) through in situ polymerization. The hydrolytic degradation starts with hydrolysis of the cross-linker, N, O-dimethacryloyl hydroxylamine, which was synthesized in house. Swelling and degradation were examined in details at a phosphate buffered saline solution at 37 °C over a 12-week period of time. To vary degradability, a co-monomer, acrylic acid (AA) or 2-hydroxypropyl methacrylamide (HPMA), was introduced, coupled with altering the concentration of the cross-linker and of the bioceramic. The co-monomer HPMA was found to be more effective than AA in enhancing degradation, though AA led to greater swelling ratios. 33% of weight loss was achieved in some of the biocomposites containing HPMA. Porous structures were developed during swelling and degradation in biocomposites with AA but not in those containing HPMA, suggesting different degradation mechanisms: bulk erosion vs. bulk degradation. Good biocompatibility, as evidenced by attachment and proliferation of mouse-derived osteoblast precursor cells from the MC3T3-E1 lineage, was observed on these biomaterials, regardless of the type of the co-monomer. The rationale and approaches employed here open up new opportunities for creating novel, complex organic-inorganic biomaterials in orthopedic tissue engineering.
pHEMA; hydrolytic degradation; N,O-dimethacryloyl hydroxylamine
With advantages such as design flexibility in modifying degradation, surface chemistry, and topography, synthetic bone–graft substitutes are increasingly demanded in orthopedic tissue engineering to meet various requirements in the growing numbers of cases of skeletal impairment worldwide. Using a combinatorial approach, we developed a series of biocompatible, hydrolytically degradable, elastomeric, bone–like biocomposites, comprising 60 wt% poly(2–hydroxyethyl methacrylate–co–methacrylic acid), poly(HEMA–co–MA), and 40 wt% bioceramic hydroxyapatite (HA). Hydrolytic degradation of the biocomposites is rendered by a degradable macromer/crosslinker, dimethacrylated poly(lactide–b–ethylene glycol–b–lactide), which first degrades to break up 3–D hydrogel networks, followed by dissolution of linear pHEMA macromolecules and bioceramic particles. Swelling and degradation were examined at Hank’s balanced salt solution at 37 °C in a 12–week period of time. The degradation is strongly modulated by altering the concentration of the co–monomer of methacrylic acid and of the macromer, and chain length/molecular weight of the macromer. 95% weight loss in mass is achieved after degradation for 12 weeks in a composition consisting of HEMA/MA/Macromer = 0/60/40, while 90% weight loss is seen after degradation only for 4 weeks in a composition composed of HEMA/MA/Macromer = 27/13/60 using a longer chain macromer. For compositions without a co–monomer, only about 14% is achieved in weight loss after 12–week degradation. These novel biomaterials offer numerous possibilities as drug delivery carriers and bone grafts particularly for low and medium load–bearing applications.
pHEMA; hydrolytic degradation; macromer
Many hydrogel materials of interest are homogeneous on the micrometer scale. Electrospinning, the formation of sub-micrometer to micrometer diameter fibers by a jet of fluid formed under an electric field, is one process being explored to create rich microstructures. However, electrospinning a hydrogel system as it reacts requires an understanding of the gelation kinetics and corresponding rheology near the liquid-solid transition. In this study, we correlate the structure of electrospun fibers of a covalently cross-linked hydrogelator with the corresponding gelation transition and kinetics. Polyethylene oxide (PEO) is used as a carrier polymer in a chemically cross-linking poly(ethylene glycol)-high molecular weight heparin (PEG-HMWH) hydrogel. Using measurements of gelation kinetics from multiple particle tracking microrheology (MPT), we correlate the material rheology with the the formation of stable fibers. An equilibrated, cross-linked hydrogel is then spun and the PEO is dissolved. In both cases, microstructural features of the electrospun fibers are retained, confirming the covalent nature of the network. The ability to spin fibers of a cross-linking hydrogel system ultimately enables the engineering of materials and microstructural length scales suitable for biological applications.
microrheology; electrospinning; hydrogels
Non-reactive, thermoplastic prepolymers (poly- methyl, ethyl and butyl methacrylate) were added to a model homopolymer matrix composed of triethylene glycol dimethacrylate (TEGDMA) to form heterogeneous networks via polymerization induced phase separation (PIPS). PIPS creates networks with distinct phase structure that can partially compensate for volumetric shrinkage during polymerization through localized internal volume expansion. This investigation utilizes purely photo-initiated, free-radical systems, broadening the scope of applications for PIPS since these processing conditions have not been studied previously.
The introduction of prepolymer into TEGDMA monomer resulted in stable, homogeneous monomer formulations, most of which underwent PIPS upon photo-irradiation, creating heterogeneous networks. During polymerization the presence of prepolymer enhanced autoacceleration, allowing for a more extensive ambient cure of the material. Phase separation, as characterized by dynamic changes in sample turbidity, was monitored simultaneously with monomer conversion and either preceded or was coincident with network gelation. Dynamic mechanical analysis shows a broadening of the tan delta peak and secondary peak formation, characteristic of phase-separated materials, indicating one phase rich in prepolymer and another depleted form upon phase separation. In certain cases, PIPS leads to an enhanced physical reduction of volumetric shrinkage, which is attractive for many applications including dental composite materials.
By use of the Dissipative Particle Dynamics (DPD) simulation technique mixtures of star-branched (arm number F = 4) and linear chains in athermal (good) solvent are analyzed regarding probabilities for intermolecular contacts of various reactive sites within different polymer coils. The accompanying sterical hindrances are described in the framework of shielding factors in order to investigate reactions and side reactions in radical polymerization and other techniques that involve polymer–polymer coupling. The shielding factors are studied as a function of total concentration from high dilution up to the bulk for different chain lengths of star-shaped and linear chains. Results indicate that their concentration dependence can be described by a power law for systems above the overlap concentration, whereas the chain length dependence vanishes when extrapolating to infinite chain lengths in that concentration range. Also the influence of the ratio of star chains and linear chains is studied for various concentrations.
Polymer reaction; Dissipative Particle Dynamics; Shielding factor
In this study, we develop thiol/acrylate two-stage reactive network forming polymer systems that exhibit two distinct and orthogonal stages of curing. Using a thiol-acrylate system with excess acrylate functional groups, a first stage polymer network is formed via a 1 to 1 stoichiometric thiol-acrylate Michael addition reaction (stage 1). At a later point in time, the excess acrylate functional groups are homopolymerized via a photoinitiated free radical polymerization to form a second stage polymer network (stage 2). By varying the monomers within the system as well as the stoichiometery of the thiol to acrylate functional groups, we demonstrate the ability of the two-stage polymer network forming systems to encompass a wide range of properties at the end of both the stage 1 and stage 2 polymerizations. Using urethane di- and hexa-acrylates within the formulations led to two-stage reactive polymeric systems with stage 1 Tgs that ranged from −12 to 30 °C. The systems were then photocured, upon which the Tg of the systems increases by up to 90 °C while also achieving a nearly 20 fold modulus increase.
Poly(β-amino ester) networks are being explored for biomedical applications, but they may lack the mechanical properties necessary for long term implantation. The objective of this study is to evaluate the effect of adding methyl methacrylate on networks' mechanical properties under simulated physiological conditions. The networks were synthesized in two parts: (1) a biodegradable crosslinker was formed from a diacrylate and amine, (2) and then varying concentrations of methyl methacrylate were added prior to photopolymerizing the network. Degradation rate, mechanical properties, and glass transition temperature were studied as a function of methyl methacrylate composition. The crosslinking density played a limited role on mechanical properties for these networks, but increasing methyl methacrylate concentration improved the toughness by several orders of magnitude. Under simulated physiological conditions, networks showed increasing toughness or sustained toughness as degradation occurred. This work establishes a method of creating degradable networks with tailorable toughness while undergoing partial degradation.
Poly(β-amino ester); Degradable; Toughness
Double hydrophilic copolymers (PEG-b-PCDs) with one PEG block and another block containing β-cyclodextrin (β-CD) units were synthesized by macromolecular substitution reaction. Via a dialysis procedure, complex assemblies with a core-shell structure were prepared using PEG-b-PCDs in the presence of a hydrophobic homopolymer poly(β-benzyl L-aspartate) (PBLA). The hydrophobic PBLA resided preferably in the cores of assemblies, while the extending PEG chains acted as the outer shell. Host-guest interaction between β-CD and hydrophobic benzyl group was found to mediate the formation of the assemblies, where PEG-b-PCD and PBLA served as the host and guest macromolecules, respectively. The particle size of the assemblies could be modulated by the composition of the host PEG-b-PCD copolymer. The molecular weight of the guest polymer also had a significant effect on the size of the assemblies. The assemblies prepared from the host and guest polymer pair were stable during a long-term storage. These assemblies could also be successfully reconstituted after freeze-drying. The assemblies may therefore be used as novel nanocarriers for the delivery of hydrophobic drugs.
Host-guest interactions; Self-assembly; β-Cyclodextrin; Core-shell nano-assemblies; Drug delivery
The objective of this work is to characterize and understand the structure-to-thermo-mechanical property relationship in thiol-ene and thiol-ene/acrylate copolymers in order to complement the existing studies on the kinetics of this polymerization reaction. Forty-one distinct three- and four-part mixtures were created with systematically varied functionality, chemical structure, type and concentration of crosslinker. The resulting polymers were subjected to dynamic mechanical analysis and tensile testing at their glass transition temperature, Tg, to quantify and understand their thermomechanical properties. The copolymer systems exhibited a broad range of Tg, rubbery modulus - Er and failure strain. The addition of a difunctional high-Tg acrylate to several three-part systems increased the resultant Tg and Er. Higher crosslink densities generally resulted in higher stress and lower strain at failure. The tunability of the thermomechanical properties of these copolymer systems is discussed in terms of inherent advantages and limitations in light of pure acrylate systems.
thiol-ene; thermomechanics; acrylate
Thermoresponsive shape memory polymers (SMPs) are a type of stimuli-sensitive materials that switch from a temporary shape back to their permanent shape upon exposure to heat. While the majority of SMPs have been fabricated in the solid form, porous SMP foams exhibit distinct properties and are better suited for certain applications, including some in the biomedical field. Like solid SMPs, SMP foams have been restricted to a limited group of organic polymer systems. In this study, we prepared inorganic–organic SMP foams based on the photochemical cure of a macromer comprised of inorganic polydimethylsiloxane (PDMS) segments and organic poly(ε-caprolactone) (PCL) segments, diacrylated PCL40-block-PDMS37-block-PCL40. To achieve tunable pore size with high interconnectivity, the SMP foams were prepared via a refined solvent-casting/particulate-leaching (SCPL) method. By varying design parameters such as degree of salt fusion, macromer concentration in the solvent and salt particle size, the SMP foams with excellent shape memory behavior and tunable pore size, pore morphology, and modulus were obtained.
Polymeric materials; Porous materials; Shape memory materials
Viability of encapsulated cells in situ crosslinkable macromonomers depends strongly on the minimum concentration of polymerization initiators and monomers required for gelation. Novel 4-arm poly(ethylene oxide-co-lactide-glycolide acrylate) (SPELGA) macromonomers were synthesized and characterized with respect to gelation, sol fraction, degradation, and swelling in aqueous solution. SPELGA macromonomers were crosslinked in the absence of N-vinyl-2-pyrrolidone (NVP) monomer to produce a hydrogel network with a shear modulus of 27±4 kPa. The shear modulus of the gels increased by 170-fold as the macromonomer concentration was increased from 10 to 25 wt%. Sol fraction ranged between 8–18%. Addition of only 0.4 mol% NVP to the polymerization mixture increased modulus by 2.2-fold from 27±4 (no NVP) to 60±10 kPa. The higher modulus was attributed to the dilution effect of polymer chains in the sol, by delaying the onset of diffusion-controlled reaction, and cross-propagation of the growing chains with network-bound SPELGA acrylates. Degradation of SPELGA gels depended on water content and density of hydrolytically degradable ester groups.
star macromonomer; degradable; gelation kinetics
Chain-transfer reactions from thiols to methacrylates are expected to delay gelation and possibly reduce stress at the bonded interface of dental restorations. Thiol additives with varying structures were combined with a dimethacrylate commonly used in dental materials. Polymerization stress/modulus development were monitored by a tensometer/rheometer, respectively, both coupled with RT-NIR. For all thiol-modified materials, conversion and modulus were 5–25 % higher than the control, and maximum reaction rate was 25–50 % lower. Gel point conversions were 12–22 % (control=5 %), and deceleration was observed at later stages in conversion (30–60 %; control=15 %). Consequently, even with increased conversion/modulus, stress values were either equal or reduced compared to the control. This approach does not require any modification in the bonding/photoactivation procedures, and seems promising for stress management not only in polymeric dental materials, but also for other applications of glassy, crosslinked photopolymers, as long as thiol volatility is addressed.
Methacrylates; gel-point conversion; polymerization stress; chain-transfer reactions; networks
The objective of this research was to examine the capabilities of QSPR (Quantitative Structure Property Relationship) modeling to predict specific biological responses (fibrinogen adsorption, cell attachment and cell proliferation index) on thin films of different polymethacrylates. Using 33 commercially available monomers it is theoretically possible to construct a library of over 40,000 distinct polymer compositions. A subset of these polymers were synthesized and solvent cast surfaces were prepared in 96 well plates for the measurement of fibrinogen adsorption. NIH 3T3 cell attachment and proliferation index were measured on spin coated thin films of these polymers. Based on the experimental results of these polymers, separate models were built for homo-, co-, and terpolymers in the library with good correlation between experiment and predicted values. The ability to predict biological responses by simple QSPR models for large numbers of polymers has important implications in designing biomaterials for specific biological or medical applications.
Combinatorial; Polymethacrylates; Quantitative Structure Property Relation (QSPR)
Electrochemical deposition of the conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT) forms thin, conductive films that are especially suitable for charge transfer at the tissue-electrode interface of neural implants. For this study, the effects of counter-ion choice and annealing parameters on the electrical and structural properties of PEDOT were investigated. Films were polymerized with various organic and inorganic counter-ions. Studies of crystalline order were conducted via X-ray diffraction (XRD). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to investigate the electrical properties of these films. X-ray photoelectron spectroscopy (XPS) was used to investigate surface chemistry of PEDOT films. The results of XRD experiments showed that films polymerized with certain small counter-ions have a regular structure with strong (100) edge-to-edge correlations of PEDOT chains at ~1.3 nm. After annealing at 170 °C for 1 hour, the XRD peaks attributed to PEDOT disappeared. PEDOT polymerized with LiClO4 as a counter-ion showed improved impedance and charge storage capacity after annealing at 160 °C.
Conducting polymers; PEDOT; XRD
A new type of pH-labile cationic polymers, poly(ortho ester amidine) (POEAmd) copolymers, has been synthesized and characterized with potential future application as gene delivery carriers. The acid-labile POEAmd copolymer was synthesized by polycondensation of a new ortho ester diamine monomer with dimethylaliphatimidates, and a non-acid-labile polyamidine (PAmd) copolymer was also synthesized for comparison using a triethylene glycol diamine monomer. Both copolymers were easily dissolved in water, and can efficiently bind and condense plasmid DNA at neutral pH, forming nano-scale polyplexes. The physico-chemical properties of the polyplexes have been studied using dynamic light scattering, gel electrophoresis, ethidium bromide exclusion, and heparin competition. The average size of the polyplexes was dependent on the amidine: phosphate (N:P) ratio of the polymers to DNA. Polyplexes containing the acid-labile POEAmd or the non-acid-labile PAmd showed similar average particle size, comparable strength of condensing DNA, and resistance to electrostatic destabilization. They also share similar metabolic toxicity to cells as measured by MTT assay. Importantly, the acid-labile polyplexes undergo accelerated polymer degradation at mildly-acid-pHs, resulting in increasing particle size and the release of intact DNA plasmid. Polyplexes from both types of polyamidines caused distinct changes in the scattering properties of Baby Hamster Kidney (BHK-21) cells, showing swelling and increasing intracellular granularity. These cellular responses are uniquely different from other cationic polymers such as polyethylenimine and point to stress-related mechanisms specific to the polyamidines. Gene transfection of BHK-21 cells was evaluated by flow cytometry. The positive yet modest transfection efficiency by the polyamidines (acid-labile and non-acid-labile alike) underscores the importance of balancing polymer degradation and DNA release with endosomal escape. Insights gained from studying such acid-labile polyamidine-based DNA carriers and their interaction with cells may contribute to improved design of practically useful gene delivery systems.
Copolymer; Ortho ester; Gene delivery
The actuation strain and speed of ionic electroactive polymer (EAP) actuators are mainly determined by the charge transport through the actuators and excess ion storage near the electrodes. We employ a recently developed theory on ion transport and storage to investigate the charge dynamics of short-side-chain Aquivion® (Hyflon®) membranes with different uptakes of ionic liquid (IL) 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMI-Tf). The results reveal the existence of a critical uptake of ionic liquids above which the membrane exhibit a high ionic conductivity (σ>5×10−2 mS/cm). Especially, we investigate the charge dynamics under voltages which are in the range for practical device operation (~1 volts and higher). The results show that the ionic conductivity, ionic mobility, and mobile ion concentration do not change with the applied voltage below 1 volt (and for σ below 4 volts). The results also show that bending actuation of the Aquivion membrane with 40 wt% EMI-Tf is much larger than that of Nafion, indicating that the shorter flexible side chains improve the electromechanical coupling between the excess ions and the membrane backbones, while not affect the actuation speed.
ionic electroactive polymer actuator; ionic liquids; Poisson-Nernst-Planck equations; Aquivion; Nafion