Synthetic Thermo-Responsive Terpolymers as Tunable Scaffolds for Cell Culture Applications.

The use of tailored synthetic hydrogels for in vitro tissue culture and biomanufacturing provides the advantage of mimicking the cell microenvironment without issues of batch-to-batch variability. To that end, this work focused on the design, characterization, and preliminary evaluation of thermo-responsive, transparent synthetic terpolymers based on N-isopropylacrylamide, vinylphenylboronic acid, and polyethylene glycol for cell manufacturing and in vitro culture applications. Polymer physical properties were characterized by FT-IR, 1H-NMR, DLS, rheology, and thermal-gravimetric analysis. Tested combinations provided polymers with a lower critical solution temperature (LCST) between 30 and 45 °C. Terpolymer elastic/shear modulus varied between 0.3 and 19.1 kPa at 37 °C. Cellular characterization indicated low cell cytotoxicity on NIH-3T3. Experiments with the ovarian cancer model SKOV-3 and Jurkat T cells showed the terpolymers' capacity for cell encapsulation without interfering with staining or imaging protocols. In addition, cell growth and high levels of pluripotency demonstrated the capability of terpolymer to culture iPSCs. Characterization results confirmed a promising use of terpolymers as a tunable scaffold for cell culture applications.

Magneto-responsive liquid crystalline elastomer nanocomposites as potential candidates for dynamic cell culture substrates.

Recently, liquid crystalline elastomers (LCEs) have been proposed as active substrates for cell culture due to their potential to attach and orient cells, and impose dynamic mechanical signals through the application of external stimuli. In this report, the preparation of anisotropic and oriented nematic magnetic-sensitized LCEs with iron oxide nanoparticles, and the evaluation of the effect of particle addition at low concentrations on the resultant structural, thermal, thermo-mechanical, and mechanical properties is presented. Phase transformations produced by heating in alternating magnetic fields were investigated in LCEs in contact with air, water, and a common liquid cell culture medium was also evaluated. The inclusion of nanoparticles into the elastomers displaced the nematic-to-isotropic phase transition, without affecting the nematic structure as evidenced by similar values of the order parameter, while reducing the maximum thermomechanical deformations. Remote and reversible deformations of the magnetic LCEs were achieved through the application of alternating magnetic fields, which induces the nematic-isotropic phase transition through nanoparticle heat generation. Formulation parameters can be modified to allow for remote actuation at values closer to the human physiological temperature range and within the range of deformations that can affect the cellular behavior of fibroblasts. Finally, a collagen surface treatment was performed to improve compatibility with NIH-3T3 fibroblast cultures, which enabled the attachment and proliferation of fibroblasts on substrates with and without magnetic particles under quiescent conditions. The LCEs developed in this work, which are able to deform and experience stress changes by remote contact-less magnetic stimulation, may allow for further studies on the effect of substrate morphology changes and dynamic mechanical properties during in vitro cell culture.

Hierarchical microstructures formed by bidisperse colloidal suspensions within colloid-in-liquid crystal gels.

Past studies have reported that colloids of a single size dispersed in the isotropic phase of a mesogenic solvent can form colloid-rich networks (and gels) upon thermal quenching of the system across the isotropic-nematic phase boundary of the mesogens. Herein we report the observation and characterization of complex hierarchical microstructures that form when bidisperse colloidal suspensions of nanoparticles (NPs; iron oxide with diameters of 188 ± 20 nm or poly(methyl methacrylate) with diameters of 150 ± 15 nm) and microparticles (MPs; polystyrene with diameters of 2.77 ± 0.20 µm) are dispersed in the isotropic phase of 4-pentyl-4'-cyanobiphenyl (5CB) and thermally quenched. Specifically, we document microstructuring that results from three sequential phase separation processes that occur at distinct temperatures during stepwise cooling of the ternary mixture from its miscibility region. The first phase transition demixes the system into coexisting MP-rich and NP-rich phases; the second promotes formation of a particle network within the MP-rich phase; and the third, which coincides with the isotropic-to-nematic phase transition of 5CB, produces a second colloidal network within the NP-rich phase. We quantified the dynamics of each demixing process by using optical microscopy and Fourier transform image analysis to establish that the phase transitions occur through (i) surface-directed spinodal decomposition, (ii) spinodal decomposition, and (iii) nucleation and growth, respectively. Significantly, the observed series of phase transitions leads to a hierarchical organization of cellular microstructures not observed in colloid-in-liquid crystal gels formed from monodisperse colloids. The results of this study suggest new routes to the synthesis of colloidal materials with hierarchical microstructures that combine large surface areas and organized porosity with potential applications in catalysis, separations, chemical sensing, or tissue engineering.

Thermal gelation of aqueous hydroxypropylmethylcellulose solutions with SDS and hydrophobic drug particles.

The thermal gelation of hydroxypropylmethylcellulose (HPMC) solutions has been studied as a function of sodium dodecyl sulfate (SDS) concentration with and without griseofulvin, a model particulate BCS Class II drug by rheological measurements of gelation temperature (Tgel), steady-state viscosity (η) at 25 °C, and ζ-potential. Polymer adsorption on the drug was demonstrated by a decrease in η and potential in the absence of SDS. Griseofulvin had a synergistic effect on gelation which was attributed to an effective spanning of associated hydrophobic polymeric regions through interactions with the adsorbed polymer. Adding SDS offsets this effect on Tgel shielding hydrophobic interactions. Higher SDS concentrations had no effect on the particles surface as evidenced by constant ζ-potential and Tgel. Yet, polymeric chains are saturated and larger surfactant aggregates account for the increase in viscosity. Understanding the gelation mechanism and complex interactions of HPMC with surfactants and drugs is necessary for the design of pharmaceutical products and optimization of their performance properties.