Nanostructured Biointerfaces: Nanoarchitectonics of Thermoresponsive Polymer Brushes Impact Protein Adsorption and Cell Adhesion

Abstract

Controlling the reversibility, quantity, and extent of biomolecule interaction at interfaces has a significant relevance for biomedical and biotechnological applications, because protein adsorption is always the first step when a solid surface gets in contact with a biological fluid. Polymer brushes, composed of end-tethered linear polymers with sufficient grafting density, are very promising to control and alter interactions with biological systems because of their unique structure and distinct collaborative response to environmental changes. We studied protein adsorption and cell adhesion at polymer brush substrates which consisted of poly(N-isopropylacrylamide) (PNIPAAm), having a lower critical solution temperature (LCST), to control bioadsorptive processes by changing the environmental temperature. Preparing the PNIPAAm brushes by the "grafting-to"-method two differently synthesized PNIPAAm polymers were used, at which one possessed an additional hydrophobic terminal headgroup. It is known that hydrophobic moieties can influence protein adsorption significantly. The films were comprehensively analyzed by in situ spectroscopic ellipsometry, contact angle measurements, streaming potential, and atomic force microscopy. Our study was mainly focused on the investigation of the fibrinogen (FGN) adsorption responsiveness both on homo polymer PNIPAAm brushes with and without the hydrophobic terminal functionalization, and further on binary brushes made of the polyelectrolyte poly(acrylic acid) (PAA) and one of the prior described two PNIPAAm species. The results show that the terminal hydrophobic modification of PNIPAAm has a considerable impact on wettability, LCST, and morphology of the homo and the binary brush systems, which consequently led to an alteration of FGN adsorption. By using binary PNIPAAm-PAA brushes with different composition it was possible to induce stimuli dependent FGN adsorption with a considerable amplified switching effect by introducing a hydrophobic terminal residue to PNIPAAm. Cell adhesion studies with human mesenchymal stem cells reflected the results of the FGN adsorption.

Materials Nanoarchitectonics as Cell Regulators

“…Avinash and Govindaraju also emphasized the importance of the nanoarchitectonics concept for functional applications of assemblies of biomolecules such as lipids, nucleobases, carbohydrates, and amino acids . Nanoarchitectonics of thermo‐responsive polymer brushes on protein adsorption and cell adhesion was reported by Uhlmann and co‐workers . They reported stimuli dependent fibrinogen adsorption and adhesion of human mesenchymal stem cells.…”

“…[14] Nanoarchitectonics of thermo-responsive polymer brushes on protein adsorption and cell adhesion was reported by Uhlmann and co-workers. [15] They reported stimuli dependent fibrinogen adsorption and adhesion of human mesenchymal stem cells.…”

Polymer brush: a promising grafting approach to scaffolds for tissue engineering

“…Stem cell studies on polymer brush have been directed toward regulating stem cell behaviors by using polymer brush itself or bioactive properties of additionally attached biopolymers (18, 21). Poly[2(methacryloyloxy)ethyl dimethyl-(3-ulfopropyl) ammonium hydroxide] (PMEDSAH) polymer brush has been shown to be able to maintain undifferentiated human embryonic stem cell (hESC) in a long-term culture (19).…”

“…Growth factors attached to poly (acrylic) acid (PAA) brush have been reported to be able to regulate the differentiation of mouse embryonic stem cell (mESC) (20). Thermoresponsive poly( N -isopropylacrylamide) (PNIPAAm) brush has been demonstrated to be able to control fibrinogen adhesion according to temperature for the study of the adhesion of human mesenchymal stem cell (hMSC) (21). Block copolymer (Pluronic F-127: PF127) brush conjugated with antimicrobial peptide and RGD peptide can effectively promote the antibacterial property and cell adhesion/spreading in tissue engineering (22).…”

Targeted grafting of thermoresponsive polymers from a penetrative honeycomb structure for cell sheet engineering

“…17 This technology has already been used in generating various organs, as in corneal surface reconstruction, in endoscopic treatment of esophageal ulceration, and in myocardial tissue reconstruction. [21][22][23] However, many studies have been performed on flat substrates. 20 Because of the inflammatory response and their cellular filling ratio faced by the former two methods, thermoresponsive pNIPAAm films have more potential use as confluent cell sheets.…”