Polymer-interface-tissue model to estimate leachable release from medical devices.

The ability to predict clinically relevant exposure to potentially hazardous compounds that can leach from polymeric components can help reduce testing needed to evaluate the biocompatibility of medical devices. In this manuscript, we compare two physics-based exposure models: 1) a simple, one-component model that assumes the only barrier to leaching is the migration of the compound through the polymer matrix and 2) a more clinically relevant, two-component model that also considers partitioning across the polymer-tissue interface and migration in the tissue away from the interface. Using data from the literature, the variation of the model parameters with key material properties were established, enabling the models to be applied to a wide range of combinations of leachable compound, polymer matrix and tissue type.

Inter-laboratory study for extraction testing of medical devices.

Biocompatibility evaluation of medical devices often relies on chemical testing according to ISO 10993-18 as a critical component for consideration. However, the precision associated with these non-targeted chemical characterization assessments has not been well established. Therefore, we have conducted a study to characterize intra-laboratory (repeatability) and inter-laboratory (reproducibility) variability associated with chemical testing of extractables from polymeric materials.

Relative effects of polymer composition and sample preparation on glass dynamics.

Modern design of common adhesives, composites and polymeric parts makes use of polymer glasses that are stiff enough to maintain their shape under a high stress while still having a ductile behavior after the yield point. Typically, material compositions are tuned with co-monomers, polymer blends, plasticizers, or other additives to arrive at a tradeoff between the elastic modulus and toughness. In contrast, strong changes to the mechanics of a glass are possible by changing only the molecular packing during vitrification or even deep in the glassy state.

Predicting Solute Diffusivity in Polymers Using Time-Temperature Superposition.

We demonstrate a novel application of the time-temperature superposition (TTS) principle to predict solute diffusivity in glassy polymers using atomistic molecular dynamics simulations. Our TTS approach incorporates the Debye-Waller factor ⟨⟩, a measure of solute caging, along with concepts from thermodynamic scaling methods, allowing us to balance contributions to the dynamics from temperature and ⟨⟩ using adjustable parameters. Our approach rescales the solute mean-squared displacement curves at several temperatures into a master curve that approximates the diffusive dynamics at a reference temperature, effectively extending the simulation time scale from nanoseconds to seconds and beyond.

Relations Between Dynamic Localization and Solute Diffusion in Polymers.

Various public health concerns can arise from the unintended leaching of additives and impurities from polymeric medical devices or food packaging, which is directly related to each solute's diffusivity . Both experimental and simulation methods can be used to quantify , but slow diffusion at physiologic temperature in glassy polymers can render these approaches impractical. Here, we investigate a simulation approach with the potential to more rapidly calculate .

Leveraging Extraction Testing to Predict Patient Exposure to Polymeric Medical Device Leachables Using Physics-based Models.

Toxicological risk assessment approaches are increasingly being used in lieu of animal testing to address toxicological concerns associated with release of chemical constituents from polymeric medical device components. These approaches currently rely on in vitro extraction testing in aggressive environments to estimate patient exposure to these constituents, but the clinical relevance of the test results is often ambiguous. Physics-based mass transport models can provide a framework to interpret extraction test results to provide more clinically relevant exposure estimates.

Identifying Nonaffine Softening Modes in Glassy Polymer Networks: A Pathway to Chemical Design.

Using molecular simulations and theory, we develop an explicit mapping of the contribution of molecular relaxation modes in glassy thermosets to the shear modulus, where the relaxations were tuned by altering the polarity of side groups. Specifically, motions at the domain, segmental, monomer, and atomic levels are taken from molecular dynamics snapshots and directly linked with the viscoelasticity through a framework based in the lattice dynamics of amorphous solids. This unique approach provides direct insight into the roles of chemical groups in the stress response, including the time scale and spatial extent of relaxations during mechanics.

Mechanics and nanovoid nucleation dynamics: effects of polar functionality in glassy polymer networks.

We use molecular simulations and experiments to rationalize the properties of a class of networks based on dicyclopentadiene (DCPD), a polymer with excellent fracture toughness and a high glass transition temperature (Tg), copolymerized with 5-norbornene-2-methanol (NBOH). DCPD is a highly non-polar hydrocarbon, while NBOH contains a hydroxy group, introducing polar functionality and hydrogen bonds (H-bonds). NBOH thus represents a possible route to improve the chemical compatibility of DCPD-based networks with less-hydrophobic materials.

Parameter-free predictions of the viscoelastic response of glassy polymers from non-affine lattice dynamics.

We study the viscoelastic response of amorphous polymers using theory and simulations. By accounting for internal stresses and considering instantaneous normal modes (INMs) within athermal non-affine theory, we make parameter-free predictions of the dynamic viscoelastic moduli obtained in coarse-grained simulations of polymer glasses at non-zero temperatures. The theoretical results show very good correspondence with rheology data collected from molecular dynamics simulations over five orders of magnitude in frequency, with some instabilities that accumulate in the low-frequency part on approach to the glass transition.

Influence of molecular weight between crosslinks on the mechanical properties of polymers formed via ring-opening metathesis.

The apparent molecular weight between crosslinks (Mc,a) in a polymer network plays a fundamental role in the network mechanical response. We systematically varied Mc,a independent of strong noncovalent bonding by using ring-opening metathesis polymerization (ROMP) to co-polymerize dicyclopentadiene (DCPD) with a chain extender that increases Mc,a or a di-functional crosslinker that decreases Mc,a. We compared the ROMP series quasi-static modulus (E), tensile yield stress (σy), and fracture toughness (KIC and GIC) in the glassy regime with literature data for more polar thermosets.

Topological structure and mechanics of glassy polymer networks.

The influence of chain-level network architecture (i.e., topology) on mechanics was explored for unentangled polymer networks using a blend of coarse-grained molecular simulations and graph-theoretic concepts.

Nanovoid formation and mechanics: a comparison of poly(dicyclopentadiene) and epoxy networks from molecular dynamics simulations.

Protective equipment in civilian and military applications requires the use of polymer materials that are both stiff and tough over a wide range of strain rates. However, typical structural materials, like tightly cross-linked epoxies, are very brittle. Recent experiments demonstrated that cross-linked poly(dicyclopentadiene) (pDCPD) networks can circumvent this trade-off by providing structural properties such as a high glass transition temperature and glassy modulus, while simultaneously exhibiting excellent toughness and high-rate impact resistance.

Effect of Hydrophobic and Hydrophilic Surfaces on the Stability of Double-Stranded DNA.

DNA hybridization is the foundation for numerous technologies like DNA origami and DNA sensing/microarrays. Using molecular simulations, enhanced-sampling methods, and free-energy calculations, we show the effects of hydrophilic and hydrophobic surfaces on DNA hybridization. Hydrophilic surfaces compete with terminal bases' H-bonds but stabilize central base stacking.

Interaction of hyaluronan binding peptides with glycosaminoglycans in poly(ethylene glycol) hydrogels.

This study investigates the incorporation of hyaluronan (HA) binding peptides into poly(ethylene glycol) (PEG) hydrogels as a mechanism to bind and retain hyaluronan for applications in tissue engineering. The specificity of the peptide sequence (native RYPISRPRKRC vs non-native RPSRPRIRYKC), the role of basic amino acids, and specificity to hyaluronan over other GAGs in contributing to the peptide-hyaluronan interaction were probed through experiments and simulations. Hydrogels containing the native or non-native peptide retained hyaluronan in a dose-dependent manner.

Molecular simulations of polycation-DNA binding exploring the effect of peptide chemistry and sequence in nuclear localization sequence based polycations.

Gene therapy relies on the delivery of DNA into cells, and polycations are one class of vectors enabling efficient DNA delivery. Nuclear localization sequences (NLS), cationic oligopeptides that target molecules for nuclear entry, can be incorporated into polycations to improve their gene delivery efficiency. We use simulations to study the effect of peptide chemistry and sequence on the DNA-binding behavior of NLS-grafted polycations by systematically mutating the residues in the grafts, which are based on the SV40 NLS (peptide sequence PKKKRKV).

Sequence-specific recognition of cancer drug-DNA adducts by HMGB1a repair protein.

The efficacy of cancer drugs such as cisplatin (Cp) and oxaliplatin (Ox), which covalently bind to DNA to form drug-DNA adducts, is linked to their recognition by repair proteins such as HMGB1a. Previous experimental studies showed that HMGB1a's binding affinity for Cp- and Ox-DNA varies with the drug used and the local DNA sequence context of the adduct. We link this differential binding affinity to the free energy of deforming (bending and minor groove opening) the drug-DNA molecule during HMGB1a binding.

Understanding the effect of polylysine architecture on DNA binding using molecular dynamics simulations.

Polycations with varying chemistries and architectures have been synthesized and used in DNA transfection. In this paper we connect poly-L-lysine (PLL) architecture to DNA-binding strength, and in turn transfection efficiency, since experiments have shown that graft-type oligolysine architectures [e.g.