Effects of Lateral Deformation by Thermoresponsive Polymer Brushes on the Measured Friction Forces

The nanotribological properties of hydrophilic polymer brushes are conveniently analyzed by lateral force microscopy (LFM). However, the measurement of friction for highly swollen and relatively thick polymer brushes can be strongly affected by the tendency of the compliant brush to be laterally deformed by the shearing probe. This phenomenon induces a “tilting” in the recorded friction loops, which is generated by the lateral bending and stretching of the grafts. In this study we highlight how the brush lateral deformation mainly affects the friction measurements of swollen PNIPAM brushes (below LCST) when relatively short scanning distances are applied. Under these conditions, the energy dissipation recorded by LFM is almost uniquely determined by stretching and bending of the compliant brush back and forth along the scanning direction, and it is not correlated to dynamic friction between two sliding surfaces. In contrast, when the scanning distance applied during LFM is relevantly longer than the brush lateral deformation, sliding of the probe on the brush interface becomes dominant, and a correct measurement of dynamic friction can be accomplished. By increasing the temperature above the LCST, the PNIPAM brushes undergo dehydration and assume a collapsed morphology, thereby hindering their lateral deformation by scanning probe. Hence, at 40 °C in water the recorded friction loops do not show any tilting and LFM accurately describes the dynamic friction between the probe and the polymer surface

Controlled Crosslinking Is a Tool To Precisely Modulate the Nanomechanical and Nanotribological Properties of Polymer Brushes

Covalent crosslinking of weak polyelectrolyte brushes widens the tuning potential for their swelling, nanomechanical, and nanotribological properties, which can be simultaneously adjusted by varying the crosslinker content and the pH of the surroundings. We demonstrate that this is especially valid for poly­(hydroxyethyl methacrylate) (PHEMA) brushes and brush hydrogels, and their ionizable, succinate-modified derivatives (PHEMA-SA), covalently crosslinked with different amounts of di­(ethylene glycol) dimethacrylate (DEGDMA) during surface-initiated atom transfer radical polymerization (SI-ATRP). Atomic force microscopy (AFM) methods highlight how pristine PHEMA films are stiff and display high coefficients of friction in water. Their succinate derivatives swell profusely in aqueous media. Under acidic conditions they are neutral, compliant, and lubricious, with apparent Young’s moduli (<i>E</i>*) lying between 10 and 30 kPa. Their contact mechanical behavior can be described by either the Johnson–Kendall–Roberts (JKR) or the Derjaguin–Müller–Toporov (DMT) model, depending on crosslinker content. In contrast, under basic conditions, brushes and brush hydrogels become charged, expand, and present a rigid, electrostatic barrier toward the AFM probe. Friction is extremely low at relatively low applied loads, whereas it increases at higher loads, to an extent that is regulated by the number of crosslinks within the films

Nanoassemblies of Tissue-Reactive, Polyoxazoline Graft-Copolymers Restore the Lubrication Properties of Degraded Cartilage

Osteoarthritis leads to an alteration in the composition of the synovial fluid, which is associated with an increase in friction and the progressive and irreversible destruction of the articular cartilage. In order to tackle this degenerative disease, there has been a growing interest in the medical field to establish effective, long-term treatments to restore cartilage lubrication after damage. Here we develop a series of graft-copolymers capable of assembling selectively on the degraded cartilage, resurfacing it, and restoring the lubricating properties of the native tissue. These comprise a polyglutamic acid backbone (PGA) coupled to brush-forming, poly-2-methyl-2-oxazoline (PMOXA) side chains, which provide biopassivity and lubricity to the surface, and to aldehyde-bearing tissue-reactive groups, for the anchoring on the degenerated cartilage <i>via</i> Schiff bases. Optimization of the graft-copolymer architecture (<i>i.e</i>., density and length of side chains and amount of tissue-reactive functions) allowed a uniform passivation of the degraded cartilage surface. Graft-copolymer-treated cartilage showed very low coefficients of friction within synovial fluid, reestablishing and in some cases improving the lubricating properties of the natural cartilage. Due to these distinctive properties and their high biocompatibility and stability under physiological conditions, cartilage-reactive graft-copolymers emerge as promising injectable formulations to slow down the progression of cartilage degradation, which characterizes the early stages of osteoarthritis

Modulation of Surface-Initiated ATRP by Confinement: Mechanism and Applications

The mechanism of surface-initiated atom transfer polymerization (SI-ATRP) of methacrylates in confined volumes is systematically investigated by finely tuning the distance between a grafting surface and an inert plane by means of nanosized patterns and micrometer thick foils. The polymers were synthesized from monolayers of photocleavable initiators, which allow the analysis of detached brushes by size-exclusion chromatography (SEC). Compared to brushes synthesized under “open” polymerization mixtures, nearly a 4-fold increase in brush molar mass was recorded when SI-ATRP was performed within highly confined reaction volumes. Correlating the SI-ATRP of methyl methacrylate (MMA), with and without “sacrificial” initiator, to that of lauryl methacrylate (LMA) and analyzing the brush growth rates within differently confined volumes, we demonstrate faster grafting kinetics with increasing confinement due to the progressive hindering of Cu^II-based deactivators from the brush propagating front. This effect is especially noticeable when viscous polymerization mixtures are generated and enables the synthesis of several hundred nanometer thick brushes within relatively short polymerization times. The faster rates of confined SI-ATRP can be additionally used to fabricate, in one pot, precisely structured brush gradients, when volume confinement is continuously varied across a single substrate by spatially tuning the vertical distance between the grafting and the confining surfaces

Engineering Lubricious, Biopassive Polymer Brushes by Surface-Initiated, Controlled Radical Polymerization

Surface-initiated controlled radical polymerization enables the fabrication of biopassive polymer brushes with interfacial, physicochemical properties that can be independently varied across a single substrate. Poly­[(oligoethylene glycol) methacrylate] (POEGMA) brushes were synthesized by surface-initiated atom transfer radical polymerization (SI-ATRP), locally varying the exposure of initiator-functionalized surfaces to the polymerization solution to yield POEGMA brush thickness gradients. A combination of variable-angle spectroscopic ellipsometry (VASE) and atomic force microscopy (AFM) demonstrated that brush swelling, grafting density, nanomechanical properties, and biopassivity towards protein adsorption all remained constant within a thickness range between 20 and 90 nm. However, the nanotribological properties of POEGMA brushes, investigated by lateral force microscopy (LFM), were found to vary progressively along the gradient, thinner brushes showing significantly lower friction than thicker and more viscoelastic grafts. The independent variation of lubricity across a biopassive brush gradient shows how SI-ATRP can be used to tailor surfaces destined for applications involving both contact with biological media and exposure to shear stresses, as is the case for tissue-replacement implants and scaffolds for tissue engineering

Hairy and Slippery Polyoxazoline-Based Copolymers on Model and Cartilage Surfaces

Comb-like polymers presenting a hydroxybenzaldehyde (HBA)-functionalized poly­(glutamic acid) (PGA) backbone and poly­(2-methyl-2-oxazoline) (PMOXA) side chains chemisorb on aminolized substrates, including cartilage surfaces, forming layers that reduce protein contamination and provide lubrication. The structure, physicochemical, biopassive, and tribological properties of PGA-PMOXA-HBA films are finely determined by the copolymer architecture, its reactivity toward the surface, i.e. PMOXA side-chain crowding and HBA density, and by the copolymer solution concentration during assembly. Highly reactive species with low PMOXA content form inhomogeneous layers due to the limited possibility of surface rearrangements by strongly anchored copolymers, just partially protecting the functionalized surface from protein contamination and providing a relatively weak lubrication on cartilage. Biopassivity and lubrication can be improved by increasing copolymer concentration during assembly, leading to a progressive saturation of surface defects across the films. In a different way, less reactive copolymers presenting high PMOXA side-chain densities form uniform, biopassive, and lubricious films, both on model aminolized silicon oxide surfaces, as well as on cartilage substrates. When assembled at low concentrations these copolymers adopt a “lying down” conformation, i.e. adhering via their backbones onto the substrates, while at high concentrations they undergo a conformational transition, assuming a more densely packed, “standing up” structure, where they stretch perpendicularly from the substrate. This specific arrangement reduces protein contamination and improves lubrication both on model as well as on cartilage surfaces

Amplified Responsiveness of Multilayered Polymer Grafts: Synergy between Brushes and Hydrogels

The responsive properties of surface-grafted polymer films in aqueous media can be amplified by covalently layering thermosensitive brushes and hydrogels. This was demonstrated by synthesizing layers of linear poly­(<i>N</i>-isopropylacrylamide) (PNIPAM) brushes, alternating with cross-linked, poly­(hydroxyethyl)­methacrylate (PHEMA) hydrogels via sequential surface-initiated atom-transfer radical polymerization (SI-ATRP) steps. Below the lower critical solution temperature (LCST) of PNIPAM, brush/hydrogel multilayered films swell similarly to linear PNIPAM homopolymer brushes, as measured by liquid ellipsometry. In contrast, above the LCST, the PHEMA hydrogel interlayer acts as stiffening element within the collapsed multilayered film, as monitored by atomic force microscopy (AFM) nanoindentation and lateral force microscopy (LFM). This translates into a 10-fold increase in Young’s modulus by the collapsed, layered films compared to PNIPAM homopolymer analogues. The (macro)­molecular continuity between the brush main chains and hydrogel constituents thus enables a chemically robust layering to form graded, quasi-3D grafted polymer architectures, which display a concerted and amplified temperature-triggered transition

Physical Networks of Metal-Ion-Containing Polymer Brushes Show Fully Tunable Swelling, Nanomechanical and Nanotribological Properties

The interaction between weak polyacid brushes and metal ions can lead to the formation of a wide variety of complex structures across the polymer grafts. In the case of poly­(hydroxyethyl methacrylate) brushes derivatized with succinate side groups (PHEMA-SA), the coordination with Zn²⁺ or Ca²⁺ species can be tuned by varying the solution pH, below and above the p<i>K</i>_a of the polyacid brush. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) indicates that Zn²⁺ ions generate relatively weak, localized monodentate bridges along PHEMA-SA grafts at basic pH. These Zn²⁺–brush conjugates swell profusely in water, are compliant and very lubricious, as observed by combining variable angle spectroscopic ellipsometry (VASE), quartz crystal microbalance with dissipation (QCM-D), and atomic force microscopy (AFM) methods. In contrast, incubation of PHEMA-SA brushes with Ca²⁺ or Zn²⁺ at acidic pH leads to the formation of more extended, bidentate linkages forming a physical network between the metal centers and the surrounding grafts. This type of coordination causes brush dehydration and the stiffening of the films, as well as high friction, due to the energy dissipation required to perturb the dense, brush physical network by the shearing AFM probe. Regulating the interaction between metal ions and ionizable polymer brushes emerges as a versatile and easily accessible tool to control the interfacial properties of grafted polymer films. The achieved modulation of nanomechanical and nanotribological characteristics is technologically relevant, in that it allows both function and performance to be tuned for widely applicable polymer coatings

Poly(2-oxazoline)–Pterostilbene Block Copolymer Nanoparticles for Dual-Anticancer Drug Delivery

Functional block copolymers based on poly­(2-oxazoline)­s are versatile building blocks for the fabrication of dual-drug delivery nanoparticles (NPs) for anticancer chemotherapy. Core–shell NPs are fabricated from diblock copolymers featuring a long and hydrophilic poly­(2-methyl-2-oxazoline) (PMOXA) block coupled to a relatively short and functionalizable poly­(2-methylsuccinate-2-oxazoline) (PMestOXA) segment. The PMOXA block stabilizes the NP dispersions, whereas the PMestOXA segment is used to conjugate pterostilbene, a natural bioactive phenolic compound that is used as lipophilic model-drug and constitutes the hydrophobic core of the designed NPs. Subsequent loading of the NPs with clofazimine (CFZ), an inhibitor of the multidrug resistance pumps typically expressed in a large variety of cancer cells, provides an additional function to their formulation. Optimization of the copolymer composition allows the design of polymer scaffolds showing low toxicity and capable of assembling into highly stable NPs dispersions at physiologically relevant pH. In addition, the incorporation of CFZ increases the stability of the NPs and stimulates their internalization by RAW 264.7 cells

Thin Polymer Brush Decouples Biomaterial’s Micro-/Nanotopology and Stem Cell Adhesion

Surface morphology and chemistry of polymers used as biomaterials, such as tissue engineering scaffolds, have a strong influence on the adhesion and behavior of human mesenchymal stem cells. Here we studied semicrystalline poly­(ε-caprolactone) (PCL) substrate scaffolds, which exhibited a variation of surface morphologies and roughness originating from different spherulitic superstructures. Substrates were obtained by varying the parameters of the thermal processing, that is, crystallization conditions. The cells attached to these polymer substrates adopted different morphologies responding to variations in spherulite density and size. In order to decouple substrate topology effects on the cells, sub-100 nm bioadhesive polymer brush coatings of oligo­(ethylene glycol) methacrylates were grafted from PCL and functionalized with fibronectin. On surfaces featuring different surface textures, dense and sub-100 nm thick brush coatings determined the response of cells, irrespective to the underlying topology. Thus, polymer brushes decouple substrate micro-/nanoscale surface topology and the adhesion of stem cells