ABSTRACT
One of the key factors influencing the mechanical properties of natural and synthetic extracellular matrices (ECM) is how large-scale 3D gel-like structures emerge from the molecular self-assembly of individual polymers. Here, structural characterization using small-angle neutron scattering (SANS) of ECM-mimicking polyisocyanopeptide (PIC) hydrogels are reported as a function of background ions across the Hofmeister series. More specifically, the process of polymer assembly is examined by probing the structural features of the heat-set gels and correlating them with their rheological and micro-mechanical properties. The molecular parameters obtained from SANS clearly show changes in polymer conformation which map onto the temperature-induced changes in rheological and micro-mechanical behavior. The formation of larger structures are linked to the formation of cross-links (or bundles), whilst the onset of their detection in the SANS is putatively linked to their concentration in the gel. These insights provide support for the 'hot-spot' gelation mechanism of PIC heat-set gels. Finally, it is found that formation of cross-links and heat-set gelling properties can be strongly influenced by ions in accordance with Hofmeister series. In practice, these results have significance since ions are inherently present in high concentration during cell culture studies; this may therefore influence the structure of synthetic ECM networks.
Subject(s)
Hot Temperature , Polymers , Hydrogels , Rheology , Scattering, Small AngleABSTRACT
BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. PATIENTS AND METHODS: A total of 60 patients, aged 37-81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). RESULTS: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. CONCLUSION: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.
ABSTRACT
Highly dense polymer chains were formed through coupling cyclic polymeric units in a sequence controlled manner. It was found that as the number of cyclic units increased the compactness substantially increased in a good solvent to a limiting value after only 12 units. This limiting value was close to that of a linear polymer chain in a θ solvent, in which polymer segment interactions with solvent are minimized. This remarkable result suggests that the unique architecture of the cyclic structure plays an important role to significantly change the polymer conformation and remain soluble in solution, which circumvents the need for cross-linking. The insight found in this work provides a physical mechanism as to why Nature uses cyclic structures in proteins to confer stability and the compacting of DNA strands to induce chromosome territories.
ABSTRACT
In this work, the use of a nanoreactor is demonstrated to rapidly prepare monodisperse polymer nanoparticles in water-based dispersion consisting of 4-arm star polymer via the R-group RAFT approach. It is shown that by heating a nanoparticle assembler above its lower critical solution temperature (LCST), stabilized nanoparticles are formed that act as a template for the 4-arm star RAFT-mediated polymerization of styrene. Monodisperse nanoparticles of size (between 40 and 90 nm) containing monodisperse polymer of desired molecular weight (30-95 k) are obtained with little star-star coupling due to compartmentalization. The nanoreactor technique allows independent control over the size and molecular weight with a 4-arm star topology.
