Poly(2-oxazoline) Matrices with Temperature-Dependent Solubility—Interactions with Water and Use for Cell Culture

Abstract

In this work, we studied the stability of matrices with temperature-dependent solubility and their interactions with water at physiological temperature for their application in cell culture in vitro. Gradient copolymers of 2-isopropyl- with 2-n-propyl-2-oxazoline (P(iPrOx-nPrOx)) were used to prepare the matrices. The comonomer ratio during polymerization was chosen such that the cloud point temperature (TCP) of the copolymer was below 37 °C while the glass transition (Tg) was above 37 °C. The role of the support for matrices in the context of their stability in aqueous solution was examined. Therefore, matrices in the form of both self-supported bulk polymer materials (fibrillar mats and molds) and polymer films supported on the silica slides were examined. All of the matrices remained undissolved when incubated in water at a temperature above TCP. For the self-supported mats and molds, we observed the loss of shape stability, but, in the case of films supported on silica slides, only slight changes in morphology were observed. For a more in-depth investigation of the origin of the shape deformation of self-supported matrices, we analyzed the wettability, thickness, and water uptake of films on silica support because the matrices remained undeformed under these conditions. It was found that, above the TCP of P(iPrOx-nPrOx), the wettability of the films decreased, but at the same time the films absorbed water and swelled. We examined how this specific behavior of the supported films influenced the culture of fibroblasts. The temperature-dependent solubility of the matrices and the possibility of noninvasive cell separation were also examined.

Poly(2-oxazoline)s as Stimuli-Responsive Materials for Biomedical Applications: Recent Developments of Polish Scientists

“…There are studies that focused on the examination of the properties of thermo-responsive-based materials, which can be successfully used for creating defined polymers with desired applications. One of them was reported in 2020 by Dworak and coworkers’ [ 104 ] investigation of the properties of gradient copolymers based on 2-isopropyl- and 2- n -propyl-2-oxazoline (poly(iPrOx-nPrOx)), as well as their temperature responsiveness and applicability as temperature-dependent-solubility (TDS) materials for cell culture in vitro. The investigation was based on the temperature-dependent cell detachment from the matrices due to temperature changes.…”

“…The main parameter examined during this study was the behavior of the obtained matrices under aqueous conditions, which imitated the human body environment. From the obtained results, one of the greatest conclusions is that the presence of solid support for matrices with temperature-dependent solubility seems to be the crucial factor for their stability [ 104 ]. In a second study, reported in 2017 by Dworak and coworkers [ 14 ] a series of thermo-responsive copolymers were synthesized by a CROP reaction.…”

The Role of Polymer Structure in Formation of Various Nano- and Microstructural Materials: 30 Years of Research in the Laboratory of Nano- and Microstructural Materials at the Centre of Polymer and Carbon Materials PAS

“…Such a physically adsorbed polymer layer binds to the support, e.g., by weak electrostatic or van der Waals interactions. In our laboratory, we studied the stability of thermoresponsive polymer layers adsorbed on silica ( Figure 8 a) for their application in cell culture in vitro [ 83 ]. The polymer layer under cell culture conditions should be dehydrated, stable and undissolved, while after cell proliferation, the polymer should dissolve and be washed out.…”

“…Another type of self-supported material with temperature-dependent behavior—polymer matrices in the form of nonwoven fibrous mats and three-dimensional molds—was prepared [ 83 , 114 ]. We aimed to obtain self-supported materials that are dehydrated, stable (preserving defined size, shape and porosity of the construct/scaffold/material) and undissolved under cell culture conditions.…”

“…The fibrous mats were rolled up while the regular shape of the molds was distorted, and they collapsed into shapeless clods. Conversely, such significant distortions of the shape were not observed in the case of matrices in the form of layers adsorbed on silica slides [ 83 ] (see Section 2.2.1 ).…”