Chemical Design of Non‐Ionic Polymer Brushes as Biointerfaces: Poly(2‐oxazine)s Outperform Both Poly(2‐oxazoline)s and PEG

Abstract

The era of poly(ethylene glycol) (PEG) brushes as a universal panacea for preventing non-specific protein adsorption and providing lubrication to surfaces is coming to an end. In the functionalization of medical devices and implants, in addition to preventing non-specific protein adsorption and cell adhesion, polymer-brush formulations are often required to generate highly lubricious films. Poly(2-alkyl-2-oxazoline) (PAOXA) brushes meet these requirements, and depending on their side-group composition, they can form films that match, and in some cases surpass, the bioinert and lubricious properties of PEG analogues. Poly(2-methyl-2-oxazine) (PMOZI) provides an additional enhancement of brush hydration and main-chain flexibility, leading to complete bioinertness and a further reduction in friction. These data redefine the combination of structural parameters necessary to design polymer-brush-based biointerfaces, identifying a novel, superior polymer formulation.

Investigation of design parameters in generating antifouling and lubricating surfaces using hydrophilic polymer brushes

“…In spite of higher Σ values, that is, a stronger overlap for PMOXA brushes in comparison to PEG brushes [Figure (b)], PMOXA chains showed higher n(H 2 O/monomer) values in comparison to PEG chains at their corresponding highest n monomer . In agreement with literature, this observation indicates a higher hydrophilicity for PMOXA, in which PMOXA chains carry more associated H 2 O molecules in comparison to PEG. The chemical structure of PMOXA (Figure ) that contains NCO repeating units leads to higher electronegativity and thus higher affinity towards H 2 O molecules.…”

“…Recently, both linear and cyclic variants of poly(2‐oxazoline) were studied by Morgese et al . which also showed long‐term stability for poly(2‐oxazoline)s, both in terms of biopassivity to nonspecific adsorption and lubrication properties . On the contrary, Ulbricht et al .…”

“…Hence, correlating the design parameters to brush properties is vital for developing efficient protective surfaces. In general, enhancement of antifouling properties of the polymer films is observed only at optimum film thickness and chain (or monomer) surface density, where the structurally‐bound H 2 O molecules via hydrogen bonding along the polymer chain are maximized . Overcrowded polymer chains lose their conformational freedom and result in a highly extended chain configuration, sometimes even leading to surface dehydration .…”

Poly(2‐Oxazoline)‐Based Functional Peptide Mimics: Eradicating MRSA Infections and Persisters while Alleviating Antimicrobial Resistance

“…[5] POX has been studied as as ubstitution for polyethylene glycol in biomedical applications for antifouling,d rug and protein conjugation, and fabricating drug carriers for long circulation time. [6] Surprisingly,POX itself is less studied as an antimicrobial agent although it has been used as either the hydrophilic backbone or satellite group within antimicrobial polymers to balance toxicity of quaternary amines that exert antibacterial properties. [7] In this study,w ed esigned peptide mimetics using POX through the carbonyl translocation strategy (Figure 1a).…”

Using Polymers to Impart Lubricity and Biopassivity to Surfaces: Are These Properties Linked?

“…A general comparison between the biopassive and nanotribological properties of PEG, different PAOXAs and poly(2-methyl-2-oxazine) (PMOZI) brushes highlights the chemical design parameters necessary for fabricating low-fouling and highly lubricating surfaces. [63] Also in this study, compositionally different brushes were assembled on metal oxide surfaces from PLL-g-X graft-copolymers, with X=PEG, poly(2-methyl-2-oxazoline) (PMOXA), PEOXA, and PMOZI (Figure 5,a). The biopassive properties of the different brushes were tested by incubating them both with FHS and bovine chondrocytes, and appeared to be strongly correlated to the hydration and chain flexibility characteristic of each brush type.…”