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 LiClO(4) as a counter-ion showed improved impedance and charge storage capacity after annealing at 160 °C.
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.
The purpose of this study is to evaluate how the toughness of photopolymerizable (meth)acrylate networks is influenced by physiological conditions. By utilizing two ternary (meth)acrylate networks, MA-co-MMA-co-PEGDMA and 2HEMA-co-BMA-co-PEGDMA, relationships between glass transition temperature (T(g)), water content and state, and toughness were studied by varying the weight ratio of the linear monomers (MA to MMA or 2HEMA to BMA). Differential scanning calorimetry and thermogravimetric analysis were performed to evaluate the thermal behavior and water content as a function of either MA or 2HEMA concentration while tensile strain-to-failure tests were performed at 37°C to determine network toughness. Both networks exhibited a maximum in toughness in PBS in the composition corresponding to a T(g) close to the testing temperature. This toughness maximum was achieved by adjusting the glass transition temperature and/or hydrophilicity through changes in chemistry. These relationships may be utilized to design tough photopolymerizable networks for use in mechanically rigorous biomedical applications.
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.
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, T(g), to quantify and understand their thermomechanical properties. The copolymer systems exhibited a broad range of T(g), rubbery modulus - E(r) and failure strain. The addition of a difunctional high-T(g) acrylate to several three-part systems increased the resultant T(g) and E(r). 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.
The copolymerization behavior and the dark polymerization kinetics of highly reactive novel acrylic monomers were compared to traditional acrylate monomers. Copolymerization of thiol functionalities with novel acrylic monomers was characterized, and it was observed that the inclusion of secondary functionalities such as carbamates, carbonates, and cyclic carbonates, in acrylic monomers significantly alters the relative reactivity of the novel acrylates with thiols. While traditional aliphatic acrylates exhibited propagation to chain transfer ratios ranging between 0.8 (± 0.1)-1.5(± 0.2), the novel acrylates characterized by secondary functionalities exhibited much higher propagation to chain transfer ratios ranging from 2.8(± 0.2)-4(± 0.2). In the dark polymerization studies, the kinetics of the novel acrylates were evaluated following cessation of the UV light. The novel acrylates exhibited extensive polymerization in the dark compared to most traditional acrylates and diacrylates. For instance, cyclic carbonate acrylate was observed to attain 35 % additional conversion in the dark when the UV light was extinguished at 35 % conversion, whereas traditional acrylates such as hexyl acrylate attained only 3 % additional conversion when the UV light was extinguished at 35 %, and a diacrylate such as HDDA attained 15 % additional conversion when the UV light was extinguished at 40 % conversion. Also, through choice of appropriate monomers, the dark polymerization studies were performed such that the polymerization rate was approximately the same at the point the light was extinguished for all these monomers. The copolymerization and dark polymerization studies support the hypothesis that the nature of the propagating species in the novel acrylates is altered as compared to traditional acrylic monomers and polymerizations.
Diffusion coefficients of small oligosaccharides within high strength poly(ethylene glycol)/poly(acrylic acid) interpenetrating network (PEG/PAA IPN) hydrogels were measured by diffusion through hydrogel slabs. The ability of hindered diffusion models previously presented in the literature to fit the experimental data is examined. A model based solely on effects due to hydrodynamics is compared to a model based solely on solute obstruction. To examine the effect of polymer volume fraction on the observed diffusion coefficients, the equilibrium volume fraction of polymer in PEG/PAA IPNs was systematically varied by changing the initial PEG polymer concentration in hydrogel precursor solutions from 20 to 50 wt./wt.%. To examine the effect of solute radius on the observed diffusion coefficients, solute radii were varied from 3.3 to 5.1 Å by measuring diffusion coefficients of glucose, a monosaccharide; maltose, a disaccharide; and maltotriose, a trisaccharide. Both the hydrodynamic and obstruction models rely on scaling relationships to predict diffusion coefficients. The proper scaling relationship for each of the hindered diffusion models is evaluated based on fits to experimental data. The scaling relationship employed is found to have a greater significance for the hydrodynamic model than the obstruction model. Regardless of the scaling relationship employed, the obstruction model provides a better fit to our experimental data than the hydrodynamic model.
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.
This work is a part of a series of publications devoted to the development of surrogate (semi-empirical) models for the prediction of fibrinogen adsorption onto polymer surfaces. Since fibrinogen is one of the key proteins involved in platelet activation and the formation of thrombosis, the modeling of fibrinogen adsorption on the surface of blood contacting medical devices is of high theoretical and practical significance. We report here, for the first time, on the incorporation three-dimensional structures of polymers obtained from atomistic simulations into conventional mesoscopic-scale calculations. Low energy conformations derived from Molecular Dynamics simulations for 45 representatives of a combinatorial library of polyarylates were used in an improved modeling procedure (referred to as "3D surrogate model") instead of simplistic two-dimensional representations of polymer structures, which were used in several previous models (collectively referred to as "2D surrogate models"). In the framework of this 3D model we created 12 model sets of polymers to account for their chirality, conformational diversity and the structural influence of a solvent. For each polymer set, three-dimensional molecular descriptors were generated and then ranked with respect to the experimental fibrinogen adsorption data by means of a Monte Carlo Decision Tree. The most significant descriptors identified by Decision Tree and the experimental dataset were utilized to predict fibrinogen adsorption using an Artificial Neural Network (ANN). The best prediction achieved by the 3D surrogate model demonstrated a noticeable improvement in the predictive quality as compared to the previously used 2D model (as evidenced by the increase in the average Pearson correlation coefficient from 0.67+/-0.13 to 0.54+/-0.12). The predictive quality of the 3D surrogate model compares favorably with the best results previously reported for extended 2D model that combines an ANN with Partial Least Squares (PLS) regression and principal component (PC) analysis. The significance of the newly developed 3D model is that it allows high accuracy prediction of fibrinogen adsorption without the need for experimentally derived descriptors and it has better predictive quality than the original 2D surrogate model due to utilization of realistic polymer representations.
The objective of this research was to study the reinforcement of electrospun nylon 6/fibrillar silicate nanocomposite nanofibers on Bis-GMA/TEGDMA dental composites. The hypothesis was that the uniform distribution of nano-scaled and highly aligned fibrillar silicate single crystals into electrospun nylon 6 nanofibers would improve the mechanical properties of the resulting nanocomposite nanofibers, and would lead to the effective reinforcement of dental composites. The nylon 6/fibrillar silicate nanocomposite nanofibers were crystalline, structurally oriented and had an average diameter of approximately 250 nm. To relatively well distribute nanofibers in dental composites, the nanofiber containing composite powders with a particle structure similar to that in interpenetration networks were prepared first, and then used to make the dental composites. The results indicated that small mass fractions (1 % and 2 %) of nanofiber impregnation improved the mechanical properties substantially, while larger mass factions (4 % and 8 %) of nanofiber impregnation resulted in less desired mechanical properties.
Degradable thiol-ene photopolymer networks were formed through radically mediated step growth reactions. Variations in the network structure were used to alter the initial and temporal moduli, mass loss profiles, and equilibrium swelling ratios. Mass loss rates varied with changes in the solvent concentration, monomer molecular weight, average monomer functionality, and concentration of degradable linkages. The time required for the networks to degrade completely ranged from 1.20 ± 0.01 to 24.5 ± 0.1 days, which corresponded to hydrolysis rates of 0.18 ± 0.01 and 0.021 ± 0.0003 days(-1). Initial moduli also varied considerably as a function of network structure, ranging from 150 ± 35 to nearly 5000 ± 100 kPa, and initial equilibrium swelling ratios ranged from 2.5 ± 0.01 to 18.7 ± 2. Collectively, these results demonstrate how the material properties and the mass loss behavior of thiol-ene networks can be independently tuned for specific applications.
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.
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%.
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.
A systematic procedure has been developed to construct a relaxed dense-phase atomistic structure of a complex amorphous polymer. The numerical procedure consists of (1) coarse graining the atomistic model of the polymer into a mesoscopic model based on an iterative algorithm for potential inversion from distribution functions of the atomistic model, (2) relaxation of the coarse grained chain using a molecular dynamics scheme, and (3) recovery of the atomistic structure by reverse mapping based on the superposition of atomistic counterparts on the corresponding coarse grained coordinates. These methods are demonstrated by their application to construct a relaxed, dense-phase model of poly(DTB succinate), which is an amorphous tyrosine-derived biodegradable polymer that is being developed for biomedical applications. Both static and dynamic properties from the coarse-grained and atomistic simulations are analyzed and compared. The coarse-grained model, which contains the essential features of the DTB succinate structure, successfully described both local and global structural properties of the atomistic chain. The effective speedup compared to the corresponding atomistic simulation is substantially above 10(2), thus enabling simulation times to reach well into the characteristic experimental regime. The computational approach for reversibly bridging between coarse-grained and atomistic models provides an efficient method to produce relaxed dense-phase all-atom molecular models of complex amorphous polymers that can subsequently be used to study and predict the atomistic-level behavior of the polymer under different environmental conditions in order to optimally design polymers for targeted applications.
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.
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.
This paper presents a new approach to study the statistics of lattice random walks in the presence of obstacles and local self-avoidance constraints (excluded volume). By excluding sequentially local interactions within a window that slides along the chain, we obtain an upper bound on the number of self-avoiding walks (SAWs) that terminate at each possible position and orientation. Furthermore we develop a technique to include the effects of obstacles. Thus our model is a more realistic approximation of a polymer chain than that of a simple lattice random walk, and it is more computationally tractable than enumeration of obstacle-avoiding SAWs. Our approach is based on the method of the lattice-motion-group convolution. We develop these techniques theoretically and present numerical results for 2-D and 3-D lattices (square, hexagonal, cubic and tetrahedral/diamond). We present numerical results that show how the connectivity constant mu changes with the length of each self-avoiding window and the total length of the chain. Quantities such as R and others such as the probability of ring closure are calculated and compared with results obtained in the literature for the simple random walk case.
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.
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.
This article describes results on using steered molecular dynamics (SMD) simulations and experimental single molecule force spectroscopy (SMFS) to investigate the relationship between hydrogen bonding and mechanical stability of a series of homodimeric β-sheet mimics. The dimers consisting of 4, 6, and 8 H-bonding sites were modeled in explicit chloroform solvent and the rupture force was studied using constant velocity SMD. The role of solvent structuring on the conformation of the dimers was analyzed and showed no significant contribution of chloroform molecules in the rupture event. The simulated stability of the dimers was validated by force data obtained with atomic force microscopy (AFM)-based SMFS in toluene. The computational model for the 8H dimer also offered insight into a possible mismatched dimer intermediate that may contribute to the lower than expected mechanical stability observed by single molecule AFM force studies. In addition, atomic level analysis of the rupture mechanism verified the dependence of mechanical strength on pulling trajectory due to the directional nature of chemical bonding under an applied force. The knowledge gained from this basic study will be used to guide further design of modular polymers having folded nanostructures through strategic programming of weak, non-covalent interactions into polymer backbones.
Tailoring the surfaces of a nanocontainer with polymer brushes that have different affinities to the components of a phase-separating polymer blend should impart self-directing properties to the nanocontainers. Such nanocontainers could then be used to deliver a variety of functional species in tunable amounts and in a site-specific manner to polymer systems. This paper describes the surface modification, subsequent characterization of nanocontainers derived from ferritin, and the effects of surface modification on their self-directing properties in a binary phase separating homopolymer blend. Wild ferritin was either PEGylated or alkylated by zero-length crosslinking to its surface carboxylate groups that were activated by carbodiimide. Modification was confirmed by ion-exchange chromatography, zeta-potential measurement, and electrospray ionization mass spectrometry. FT-IR spectrometry was used to quantify the extent of PEGylation by ratioing the intensity of the C-O-C asymmetric stretching vibration from the grafted PEG to that of the carbonyl stretching vibration (amide I band) from the protein. Importantly, modified ferritin was soluble in the organic solvent dichloromethane (DCM). Modified ferritin was introduced into a polymer blend of hydrophobic and hydrophilic polymers made up of poly (desaminotyrosyl tyrosine dodecyl ester carbonate) (PDTD) and PEG by solvent casting from solution in the common solvent DCM. Polymer thin films with an average thickness of ~ 200 mum were obtained upon evaporation of the solvent. Transmission electron micrographs of microtomed polymer films demonstrated remarkable selectivity of PEGylated ferritin to PEG domains, while alkylated ferritin self-directs to the PDTD matrix.
Hydration- and temperature-induced microphase separations were investigated by simultaneous small- and wide-angle X-ray scattering (SAXS and WAXS) and differential scanning calorimetry (DSC) in a family of copolymers in which hydrophilic poly(ethylene glycol) (PEG) blocks are inserted randomly into a hydrophobic polymer made of either desaminotyrosyl-tyrosine ethyl ester (DTE) or iodinated I(2)DTE segments. Iodination of the tyrosine rings in I(2)DTE increased the X-ray contrast between the hydrophobic and hydrophilic segments in addition to facilitating the study of the effect of iodination on microphase separation. The formation of phase-separated, hydrated PEG domains is of considerable significance as it profoundly affects the polymer properties. The copolymers of DTE (or I(2)DTE) and PEG are a useful model system and the findings presented here may be applicable to other PEG-containing random copolymers as well. In copolymers of PEG and DTE and I(2)DTE, the presence of PEG depressed the glass transition temperature (T(g)) of the copolymer relative to the homopolymer, poly(DTE carbonate), and the DTE/ I(2)DTE segments hindered the crystallization of the PEG segments. In the dry state, at large PEG fractions (> 70 vol%), the PEG domains self-assembled into an ordered structure with 14-18 nm distance between the domains. These domains gave rise to a SAXS peak at all temperatures in the iodinated polymers, but only above the T(g) in non-iodinated polymers, due to the unexpected contrast- match between the crystalline PEG domains and the glassy DTE segments. Irrespective of whether PEG was crystalline or not, immersion of these copolymers in water resulted in the formation of hydrated PEG domains that were 10-20 nm apart. Since both water and the polymer chains must be mobile for the phase separation to occur, the PEG domains disappeared when the water froze, and reappeared as the ice began to melt. This transformation was reversible, and showed hysteresis as did the melting of ice and freezing of the water incorporated into the polymer. PEG-water complexes and PEG-water eutectics were observed in WAXS and DSC scans, respectively.
A semi-empirical method based on the mass-per-flexible-bond (M/f) principle was used to quantitatively explain the large range of glass transition temperatures (T(g)) observed in a library of 132 L-tyrosine derived homo, co- and terpolymers containing different functional groups. Polymer class specific behavior was observed in T(g) vs. M/f plots, and explained in terms of different densities, steric hindrances and intermolecular interactions of chemically distinct polymers. The method was found to be useful in the prediction of polymer T(g). The predictive accuracy was found to range from 6.4 to 3.7 K, depending on polymer class. This level of accuracy compares favorably with (more complicated) methods used in the literature. The proposed method can also be used for structure prediction of polymers to match a target T(g) value, by keeping the thermal behavior of a terpolymer constant while independently choosing its chemistry. Both applications of the method are likely to have broad applications in polymer and (bio)material science.
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.
High molecular weight, high functionality diamino telechelic polybutadienes (TPBs) were synthesized by ring-opening metathesis polymerization (ROMP) of 1,5-cyclooctadiene (COD) in the presence of a chain transfer agent, 1,8-dicyano-4-octene, followed by lithium aluminum hydride reduction. Melt coupling of diamino TPB with anhydride-terminated polystyrene (PS-anh) resulted in the formation of styrene-butadiene-styrene (SBS) triblock copolymers; ca. 80% maximum conversion of PS-anh was achieved within 30 seconds. The results from SAXS, TEM, and rheological measurements of the coupling products confirmed the formation of SBS triblock copolymers having lamellar morphology. A fluororesent-labeled PS-anh was used to study the coupling kinetics by diluting the reactants by the addition of non-functional PS.
We present a material design strategy of combining crystallinity and crosslinking to control the mechanical properties of polymeric biomaterials. Three polycaprolactone fumarates (PCLF530, PCLF1250, and PCLF2000) synthesized from the precursor polycaprolactone (PCL) diols with nominal molecular weights of 530, 1250, and 2000 g.mol(-1), respectively, were employed to fabricate polymer networks via photo-crosslinking process. Five different amounts of photo-crosslinking initiator were applied during fabrication in order to understand the role of photoinitiator in modulating the crosslinking characteristics and physical properties of PCLF networks. Thermal properties such as glass transition temperature (T(g)), melting temperature (T(m)), and degradation temperature (T(d)) of photo-crosslinked PCLFs were examined and correlated with their rheological and mechanical properties.
The effect of polymer composition and polymerization parameters such as comonomers, crosslinking ratio, and polymerization method, on the surface characteristics, surface chemistry, and swelling response of crosslinked 2-(diethylaminoethyl methacrylate) (DEAEM) and polyethylene glycol monoethyl ether monomethacrylate (PEGMMA) nanogels was studied. A novel inverse-emulsion polymerization method was developed, which formed latex nanoparticles on the order of 100-400 nm. The properties of these nanogels were compared to microparticles synthesized via solution polymerization. The new polymerization method allowed the incorporation of PEG surface tethers of lengths 400 Da up to 2000 Da. Surface tethers successfully decreased the ζ-potential of these nanogels from 70 mV to 30 mV in acidic conditions and from -60 mV to 2 mV in basic media. Nanogels swelled from 100 nm in basic media to 800 nm in acidic media due to the protonation of the tertiary amine on DEAEM.
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.
The aim of this study was to investigate the preparation, characterization, and encapsulation/release performance of an electrospun composite nanofiber mat. The hypothesis was that the composite nanofiber mat with nano-scaled drug particles impregnated in biocompatible and biodegradable polymer nanofibers can serve as an innovative type of tissue engineering scaffold with desired and controllable drug encapsulation/release properties. To test the hypothesis, the composite nanofiber mat electrospun from an emulsion consisting of poly (lactic-co-glycolic acid) (PLGA) Rhodamine B (a model compound to simulate drugs), sorbitan monooleate (Span-80, a non-ionic emulsifier/surfactant that is presumably non-toxic/safe for cell-growth), chloroform, DMF, and distilled water was prepared and characterized; and the Rhodamine B encapsulation/release profile in phosphate buffered saline (pH = 7.4) was recorded and analyzed. For comparison purposes, two additional nanofiber mats electrospun from (1) a solution containing PLGA and Rhodamine B, and (2) a solution containing PLGA, Rhodamine B, and Span-80 were also prepared and assessed as the control samples. The results indicated that the composite nanofiber mat electrospun from the emulsion had the most desired and controllable Rhodamine B encapsulation/release profile and the excellent morphological sustainability; thus, it could be utilized as both a drug encapsulation/release vehicle and a tissue engineering scaffold.
We present a unified method to generate conformational statistics which can be applied to any of the classical discrete-chain polymer models. The proposed method employs the concepts of Fourier transform and generalized convolution for the group of rigid-body motions in order to obtain probability density functions of chain end-to-end distance. In this paper, we demonstrate the proposed method with three different cases: the freely-rotating model, independent energy model, and interdependent pairwise energy model (the last two are also well-known as the Rotational Isomeric State model). As for numerical examples, for simplicity, we assume homogeneous polymer chains. For the freely-rotating model, we verify the proposed method by comparing with well-known closed-form results for mean-squared end-to-end distance. In the interdependent pairwise energy case, we take polypeptide chains such as polyalanine and polyvaline as examples.
Polypyrrole (PPy) is a biocompatible, electrically conductive polymer that has great potential for battery, sensor, and neural implant applications. Its amorphous structure and insolubility, however, limit the experimental techniques available to study its structure and properties at the atomic level. Previous theoretical studies of PPy in bulk are also scarce. Using ab initio calculations, we have constructed a molecular mechanics force field of chloride-doped PPy (PPyCl) and undoped PPy. This model has been designed to integrate into the OPLS force field, and parameters are available for the Gromacs and TINKER software packages. Molecular dynamics (MD) simulations of bulk PPy and PPyCl have been performed using this force field, and the effects of chain packing and electrostatic scaling on the bulk polymer density have been investigated. The density of flotation of PPyCl films has been measured experimentally. Amorphous X-ray diffraction of PPyCl was obtained and correlated with atomic structures sampled from MD simulations. The force field reported here is foundational for bridging the gap between experimental measurements and theoretical calculations for PPy based materials.
The osmotic and scattering properties of hyaluronan-based composite hydrogels composed of stiff biopolymer chains (carboxymethylated thiolated hyaluronan (CMHA-S)) crosslinked by a flexible polymer (polyethylene glycol diacrylate (PEGDA)) are investigated and analyzed in terms of the scaling theory. The total pre-gel polymer weight concentration is varied between 0.5 wt.% and 3.2 wt.%, while the mole ratio between the reactive PEG chain ends and the thiolated HA moieties is changed between 0.15 and 1.0. The shear modulus G of the fully swollen gels exhibits a stronger dependence on pre-gel concentration than on the crosslink density. Osmotic deswelling measurements reveal that the osmotic mixing pressure depends on the weight ratio CMHA-S/PEGDA, and is practically unaffected by the pre-gel concentration. Small-angle neutron scattering observations indicate that the thermodynamic properties of these composite gels are governed by total polymer concentration, i.e., specific interactions between the two polymeric components do not play a significant role.
This paper presents a new algorithm for generating the conformational statistics of lattice polymer models. The inputs to the algorithm are the distributions of poses (positions and orientations) of reference frames attached to sequentially proximal bonds in the chain as it undergoes all possible torsional motions in the lattice. If z denotes the number of discrete torsional motions allowable around each of the n bonds, our method generates the probability distribution in end-to-end pose corresponding to all of the z(n) independent lattice conformations in O(n(D) (+1)) arithmetic operations for lattices in D-dimensional space. This is achieved by dividing the chain into short segments and performing multiple generalized convolutions of the pose distribution functions for each segment. The convolution is performed with respect to the crystallographic space group for the lattice on which the chain is defined. The formulation is modified to include the effects of obstacles (excluded volumes), and to calculate the frequency of the occurrence of each conformation when the effects of pairwise conformational energy are included. In the latter case (which is for 3 dimensional lattices only) the computational cost is O(z(4)n(4)). This polynomial complexity is a vast improvement over the O(z(n)) exponential complexity associated with the brute force enumeration of all conformations. The distribution of end-to-end distances and average radius of gyration are calculated easily once the pose distribution for the full chain is found. The method is demonstrated with square, hexagonal, cubic and tetrahedral lattices.
Ultra-high molecular weight polyethylene (UHMWPE) is radiation cross-linked to decrease wear in total joint applications. Irradiation decreases the strength of UHMWPE and introduces residual free radicals, which can cause oxidation in the long-term. We advanced a method eliminating the free radicals without a reduction in strength. UHMWPE exhibits a hexagonal phase at high pressure and temperature, where chain mobility in the crystalline phase is increased, leading to the formation of extended chain crystals. We hypothesized that the increased chain mobility during transformation from the orthorhombic to hexagonal phase could be used to eliminate the residual free radicals in irradiated UHMWPE. We eliminated the free radicals in 25-, 65- and 100-kGy irradiated UHMWPE and these materials did not show oxidation after accelerated aging. The ultimate tensile strength and work to failure of 25 and 65-kGy irradiated UHMWPEs were improved significantly while that of 100-kGy irradiated UHMWPE was lower compared to irradiated UHMWPE melted at ambient pressure.
A new method for predicting protein secondary structure from amino acid sequence has been developed. The method is based on multiple sequence alignment of the query sequence with all other sequences with known structure from the protein data bank (PDB) by using BLAST. The fragments of the alignments belonging to proteins from the PBD are then used for further analysis. We have studied various schemes of assigning weights for matching segments and calculated normalized scores to predict one of the three secondary structures: α-helix, β-sheet, or coil. We applied several artificial intelligence techniques: decision trees (DT), neural networks (NN) and support vector machines (SVM) to improve the accuracy of predictions and found that SVM gave the best performance. Preliminary data show that combining the fragment mining approach with GOR V (Kloczkowski et al, Proteins 49 (2002) 154-166) for regions of low sequence similarity improves the prediction accuracy.
Polymerization volume change (PVC) was measured systematically using mercury dilatometry for 41 epoxide and methacrylate monomers with quartz filler. Quantitative structure property relationship (QSPR) models were developed based on this previously unreported data to gain insight in the data collection method for future models. Successful models included only data from those samples which polymerized to hardness. The most significant descriptors in these models related to monomer reactivity. In contrast, PVC data collected under experimental conditions which maximized monomer conversion resulted in descriptors describing size and branching, indicating conversion must be considered for future PVC measurements. A Rule of Mixtures (ROM) correction term improved correlations of the dilatometer data with varying quartz content, and an adjustment for conversion may similarly enable inclusion of data which had not polymerize to hardness.
Smart biomaterials composed of pH responsive polymers, poly((meth)acrylic acid), were synthesized using a precipitation polymerization technique. The microparticles were grafted with poly(ethylene glycol) (PEG) chains that are capable of complexing with the hydroxyl groups of the polyacid and interpenetrating into the mucus gel layer upon entry into the small intestine. Upon introduction of an alkaline solution, these materials imbibe a significant amount of water and create a highly viscous suspension. These materials have the necessary physicochemical properties to serve as mucoadhesive controlled release drug carriers for the oral delivery of drugs.
The elastic shear modulus G and swelling pressure ω are studied for a basic, pH-responsive hydrogel synthesized by crosslinking copolymerization of co-monomers hydroxypropyl methacrylate and N,N-dimethylaminoethyl methacrylate with crosslinker tetraethylene glycol dimethacrylate. Under normal conditions of use as a "smart" material, hydrogel swelling ratio Q and pH vary simultaneously, but here G and ω values are presented as a function of pH with Q held constant and vice-versa. At fixed pH, G decreases with increase in Q in a power law dependence, as predicted by the Flory-Rehner model. However, at fixed Q, G increases with decrease in pH (i.e, increase in degree of ionization). The pH effect is more pronounced than the volume effect, thus the hydrogel stiffens as it swells in response to pH change. At high pH, ω values of the uncharged hydrogel obey the Flory-Rehner model, whereas explicit ionic contributions can be identified at lower pH values.
In this study we introduce the use of thiol-ene photopolymers as shape memory polymer systems. The thiol-ene polymer networks are compared to a commonly utilized acrylic shape memory polymer and shown to have significantly improved properties for two different thiol-ene based polymer formulations. Using thermomechanical and mechanical analysis, we demonstrate that thiol-ene based shape memory polymer systems have comparable thermomechanical properties while also exhibiting a number of advantageous properties due to the thiol-ene polymerization mechanism which results in the formation of a homogenous polymer network with low shrinkage stress and negligible oxygen inhibition. The resulting thiol-ene shape memory polymer systems are tough and flexible as compared to the acrylic counterparts. The polymers evaluated in this study were engineered to have a glass transition temperature between 30 and 40 °C, exhibited free strain recovery of greater than 96% and constrained stress recovery of 100%. The thiol-ene polymers exhibited excellent shape fixity and a rapid and distinct shape memory actuation response.
The development of thiol-ene/thiol-epoxy hybrid networks offers the advantage of tailorable polymerization kinetics while producing a highly crosslinked, high T(g) polymer that has significantly reduced shrinkage stress. Stoichiometric mixtures of pentaerythritol tetra(3-mercaptopropionate) (PETMP)/triallyl-1,3,5-triazine-2,4,6-trione (TATATO) (thiol-ene, mixture 1) and PETMP/bisphenol a diglycidyl ether (BADGE) (thiol-epoxy, mixture 2) were prepared and hybrid mixtures of 75/25, 50/50, 25/75, and 10/90 w/w of mixtures 1 and 2 were polymerized using a combination of both radical and anionic initiation. The light exposure timing and the relative initiation conditions of the two types were used to control the order and relative rates of the radical and anionic polymerizations. The 50/50 w/w thiol-ene/thiol-epoxy hybrid material exhibited a final stress of only 0.2 MPa, which is 90 % lower than the stress developed in a control dimethacrylate resin. Kinetic analysis indicates composition affects network development in thiol-ene/thiol-epoxy hybrid networks and produces materials with robust mechanical properties.
Surface modification by surface-mediated polymerization necessitates control of the grafted polymer film thicknesses to achieve the desired property changes. Here, a microarray format is used to assess a range of reaction conditions and formulations rapidly in regards to the film thicknesses achieved and the polymerization behavior. Monomer formulations initiated by eosin conjugates with varying concentrations of poly(ethylene glycol) diacrylate (PEGDA), N-methyldiethanolamine (MDEA), and 1-vinyl-2-pyrrolidone (VP) were evaluated. Acrylamide with MDEA or ascorbic acid as a coinitiator was also investigated. The best formulation was found to be 40 wt% acrylamide with MDEA which yielded four to eight fold thicker films (maximum polymer thickness increased from 180 nm to 1420 nm) and generated visible films from 5-fold lower eosin surface densities (2.8 vs. 14 eosins/µm(2)) compared to a corresponding PEGDA formulation. Using a microarray format to assess multiple initiator surface densities enabled facile identification of a monomer formulation that yields the desired polymer properties and polymerization behavior across the requisite range of initiator surface densities.
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.
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 T(g)s that ranged from -12 to 30 °C. The systems were then photocured, upon which the T(g) of the systems increases by up to 90 °C while also achieving a nearly 20 fold modulus increase.
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.
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.
The crystallization and melting of poly(ethylene oxide) (PEO) have been examined in detail using polarized light microscopy (PLM), polarized infrared microspectroscopy (PIRM) and differential scanning calorimetry (DSC). Examination of the orientation of the crystalline stems within the spherulites by PIRM supports the hypothesis that the dominant crystal growth face of PEO changes from the (010) crystallographic plane at crystallization temperatures (Tc) > 51°C to the (120) plane at Tc > 51°C. The cusp in the logarithmic growth rate—temperature plot appears to be the result of this phenomenon. Analysis of spherulitic growth rate data for the monodisperse sample (Mw = 1.8 × 105) fails to provide evidence in support of the regime II/III transition proposed in a previous literature study and indicates that in the range 45–56°C crystallization occurs solely within regime III. The larger value for the product of the lateral and fold surface free energies in the case of (010) growth appears to arise from the higher fold surface free energ' of this growth face. The difference in the fold surface free energies of the different growth faces, 41 erg/cm2 for the (010) face as compared with 29 erg/cm2 for the (120) face, can be accounted for by the corresponding differences in the minimum chain length required for chain folding in the case of adjacent re-entry.