Switching it Up: The Promise of Stimuli-Responsive Polymer Systems in Biomedical Science.

Responsive polymer systems have the ability to change properties or behavior in response to external stimuli. The properties of responsive polymer systems can be fine-tuned by adjusting the stimuli, enabling tailored responses for specific applications. These systems have applications in drug delivery, biosensors, tissue engineering, and more, as their ability to adapt and respond to dynamic environments leads to improved performance. However, challenges such as synthesis complexity, sensitivity limitations, and manufacturing issues need to be addressed for successful implementation. In our review, we provide a comprehensive summary on stimuli-responsive polymer systems, delving into the intricacies of their mechanisms and actions. Future developments should focus on precision medicine, multifunctionality, reversibility, bioinspired designs, and integration with advanced technologies, driving the dynamic growth of sensitive polymer systems in biomedical applications.

Thermoresponsive Smart Copolymer Coatings Based on P(NIPAM-co-HEMA) and P(OEGMA-co-HEMA) Brushes for Regenerative Medicine.

The fabrication of multifunctional, thermoresponsive platforms for regenerative medicine based on polymers that can be easily functionalized is one of the most important challenges in modern biomaterials science. In this study, we utilized atom transfer radical polymerization (ATRP) to produce two series of novel smart copolymer brush coatings. These coatings were based on copolymerizing 2-hydroxyethyl methacrylate (HEMA) with either oligo(ethylene glycol) methyl ether methacrylate (OEGMA) or N-isopropylacrylamide (NIPAM). The chemical compositions of the resulting brush coatings, namely, poly(oligo(ethylene glycol) methyl ether methacrylate-co-2-hydroxyethyl methacrylate) (P(OEGMA-co-HEMA)) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-co-HEMA)), were predicted using reactive ratios of the monomers. These predictions were then verified using time-of-flight-secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). The thermoresponsiveness of the coatings was examined through water contact angle (CA) measurements at different temperatures, revealing a transition driven by lower critical solution temperature (LCST) or upper critical solution temperature (UCST) or a vanishing transition. The type of transition observed depended on the chemical composition of the coatings. Furthermore, it was demonstrated that the transition temperature of the coatings could be easily adjusted by modifying their composition. The topography of the coatings was characterized using atomic force microscopy (AFM). To assess the biocompatibility of the coatings, dermal fibroblast cultures were employed, and the results indicated that none of the coatings exhibited cytotoxicity. However, the shape and arrangement of the cells were significantly influenced by the chemical structure of the coating. Additionally, the viability of the cells was correlated with the wettability and roughness of the coatings, which determined the initial adhesion of the cells. Lastly, the temperature-induced changes in the properties of the fabricated copolymer coatings effectively controlled cell morphology, adhesion, and spontaneous detachment in a noninvasive, enzyme-free manner that was confirmed using optical microscopy.

pH-Controlled fluorescence switching in water-dispersed polymer brushes grafted to modified boron nitride nanotubes for cellular imaging.

pH-Switchable, fluorescent, hybrid, water-dispersible nanomaterials based on boron nitride nanotubes (BNNTs) and grafted copolymer brushes (poly(acrylic acid-co-fluorescein acrylate) - P(AA-co-FA)) were successfully fabricated in a two-step process. The functionalization of BNNTs was confirmed by spectroscopic, gravimetric and imaging techniques. In contrast to "pure" BNNTs, P(AA-co-FA)-functionalized BNNTs demonstrate intense green fluorescence emission at 520 nm. Under neutral or alkaline pH values, P(AA-co-FA)-functionalized BNNTs are highly emissive in contrast to acidic pH conditions where the fluorescent intensity is absent or low. No increase in the absorption was observed when the suspension pH was increased from 7 to 10. The functionalized BNNTs are easily taken up by human normal prostate epithelium (PNT1A) and human prostate cancer cell lines (DU145) and are suitable for further evaluation in cellular imaging applications.

Temperature and pH dual-responsive POEGMA-based coatings for protein adsorption.

Poly(oligo(ethylene glycol)ethyl ether methacrylate (POEGMA246) coatings were successfully fabricated using novel approach via polymerization from oligoperoxide grafted to premodified glass substrate. Wettability, content and composition of coatings fabricated with different polymerization times were determined using contact angle measurements, ellipsometry and Time of Flight-Secondary Ion Mass Spectrometry (TOF-SIMS). Thermo- and pH-responsive properties of POEGMA246 coatings were found to depend significantly on concentration of the grafted POEGMA246. Coatings fabricated with polymerization time 30 h exhibit not only temperature- but also pH-dependence of wettability. Thermal response of wettability, measured between 20 and 32°C, was prominent at pH 9 and 7 and diminished or was absent at pH 5 and 3, indicating a transition between hydrated loose coils and hydrophobic collapsed chains, blocked at low pH. Protein adsorption, observed by fluorescence microscopy and analyzed semi-quantitatively using integral geometry approach, decreased dramatically for model protein (lentil lectin labeled with fluorescein isothiocyanate) at transition from pH 5 to pH 9, showing only very weak thermal-dependence. Strong protein adsorption response to pH and very weak one to temperature was confirmed by TOF-SIMS and Principal Component Analysis.

Temperature and pH dual-responsive coatings of oligoperoxide-graft-poly(N-isopropylacrylamide): wettability, morphology, and protein adsorption.

Poly(N-isopropylacrylamide) (PNIPAM) coatings attached to glass with novel approach involving polymerization from oligoperoxide grafted to surface with (3-aminopropyl)triethoxysilane exhibit not only temperature- but also pH-dependence of wettability and protein adsorption. Wettability and composition of coatings, fabricated with different polymerization times, were determined using contact angle measurements and Time Of Flight-Secondary Ion Mass Spectrometry (TOF-SIMS), respectively. Thermal response of wettability, measured between 20 and 40°C, was prominent at pH 9 and 7 and diminished or absent at pH 5 and 3. This indicates a transition between hydrated loose coils and hydrophobic collapsed chains that is blocked at low pH. Higher surface roughness and dramatically increased adsorption of model protein (lentil lectin labeled with fluorescein isothiocyanate) were observed with AFM and fluorescence microscopy to occur in hydrophobic phases (at pH 3, for pH varied at constant temperature of 22°C and at ∼33°C, for temperature varied at constant pH 9). Protein adsorption response to pH was confirmed by TOF-SIMS and Principal Component Analysis.