Thiolated poly(2-hydroxyethyl methacrylate) hydrogels as a degradable biocompatible scaffold for tissue engineering.

Research of degradable hydrogel polymeric materials exhibiting high water content and mechanical properties resembling tissues is crucial not only in drug delivery systems but also in tissue engineering, medical devices, and biomedical-healthcare sensors. Therefore, we newly offer development of hydrogels based on poly(2-hydroxyethyl methacrylate-co-2-(acetylthio) ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) [P(HEMA-ATEMA-MPC)] and optimization of their mechanical and in vitro and in vivo degradability. P(HEMA-ATEMA-MPC) hydrogels differed in chemical composition, degree of crosslinking, and starting molar mass of polymers (15, 19, and 30 kDa). Polymer precursors were synthesized by a reversible addition fragmentation chain transfer (RAFT) polymerization using 2-(acetylthio)ethyl methacrylate containing protected thiol groups, which enabled crosslinking and gel formation. Elastic modulus of hydrogels increased with the degree of crosslinking (Slaughter et al., 2009) [1]. In vitro and in vivo controlled degradation was confirmed using glutathione and subcutaneous implantation of hydrogels in rats, respectively. We proved that the hydrogels with higher degree of crosslinking retarded the degradation. Also, albumin, γ-globulin, and fibrinogen adsorption on P(HEMA-ATEMA-MPC) hydrogel surface was tested, to simulate adsorption in living organism. Rat mesenchymal stromal cell adhesion on hydrogels was improved by the presence of RGDS peptide and laminin on the hydrogels. We found that rat mesenchymal stromal cells proliferated better on laminin-coated hydrogels than on RGDS-modified ones.

Fluorine-Containing Block and Gradient Copoly(2-oxazoline)s Based on 2-(3,3,3-Trifluoropropyl)-2-oxazoline: A Quest for the Optimal Self-Assembled Structure for 19F Imaging.

The use of fluorinated contrast agents in magnetic resonance imaging (MRI) facilitates improved image quality due to the negligible amount of endogenous fluorine atoms in the body. In this work, we present a comprehensive study of the influence of the amphiphilic polymer structure and composition on its applicability as contrast agents in 19F MRI. Three series of novel fluorine-containing poly(2-oxazoline) copolymers and terpolymers, hydrophilic-fluorophilic, hydrophilic-lipophilic-fluorophilic, and hydrophilic-thermoresponsive-fluorophilic, with block and gradient distributions of the fluorinated units, were synthesized. It was discovered that the CF3 in the 2-(3,3,3-trifluoropropyl)-2-oxazoline (CF3EtOx) group activated the cationic chain end, leading to faster copolymerization kinetics, whereby spontaneous monomer gradients were formed with accelerated incorporation of 2-methyl-2-oxazoline or 2-n-propyl-2-oxazoline with a gradual change to the less-nucleophilic CF3EtOx monomer. The obtained amphiphilic copolymers and terpolymers form spherical or wormlike micelles in water, which was confirmed using transmission electron microscopy (TEM), while small-angle X-ray scattering (SAXS) revealed the core-shell or core-double-shell morphologies of these nanoparticles. The core and shell sizes obey the scaling laws for starlike micelles predicted by the scaling theory. Biocompatibility studies confirm that all copolymers obtained are noncytotoxic and, at the same time, exhibit high sensitivity during in vitro 19F MRI studies. The gradient copolymers provide the best 19F MRI signal-to-noise ratio in comparison with the analogue block copolymer structures, making them most promising as 19F MRI contrast agents.

Microscopic Structure of Swollen Hydrogels by Scanning Electron and Light Microscopies: Artifacts and Reality.

The exact knowledge of hydrogel microstructure, mainly its pore topology, is a key issue in hydrogel engineering. For visualization of the swollen hydrogels, the cryogenic or high vacuum scanning electron microscopies (cryo-SEM or HVSEM) are frequently used while the possibility of artifact-biased images is frequently underestimated. The major cause of artifacts is the formation of ice crystals upon freezing of the hydrated gel. Some porous hydrogels can be visualized with SEM without the danger of artifacts because the growing crystals are accommodated within already existing primary pores of the gel. In some non-porous hydrogels the secondary pores will also not be formed due to rigid network structure of gels that counteracts the crystal nucleation and growth. We have tested the limits of true reproduction of the hydrogel morphology imposed by the swelling degree and mechanical strength of gels by investigating a series of methacrylate hydrogels made by crosslinking polymerization of glycerol monomethacrylate and 2-hydroxyethyl methacrylate including their interpenetrating networks. The hydrogel morphology was studied using cryo-SEM, HVSEM, environmental scanning electron microscopy (ESEM), laser scanning confocal microscopy (LSCM) and classical wide-field light microscopy (LM). The cryo-SEM and HVSEM yielded artifact-free micrographs for limited range of non-porous hydrogels and for macroporous gels. A true non-porous structure was observed free of artifacts only for hydrogels exhibiting relatively low swelling and high elastic modulus above 0.5 MPa, whereas for highly swollen and/or mechanically weak hydrogels the cryo-SEM/HVSEM experiments resulted in secondary porosity. In this contribution we present several cases of severe artifact formation in PHEMA and PGMA hydrogels during their visualization by cryo-SEM and HVSEM. We also put forward empirical correlation between hydrogel morphological and mechanical parameters and the occurrence and intensity of artifacts.