Fabrication of Biopassive Surfaces Using Poly(2‐alkyl‐2‐oxazoline)s: Recent Progresses and Applications

Abstract

monomer composition enables to obtain hydrophilic and bioinert and/or amphiphilic PAOXA species displaying thermoresponsive properties. [6] Simultaneously, careful choice of initiator and/or terminator agents gives access to end-functional or heterobifunctional polymers, which can be directly applied for surface modification, or used as building blocks to yield structurally more complex adsorbates targeting specific substrates or generating well-defined polymer architectures at the interface. [7-9] Among the most recent studies focusing on the fabrication of biopassive PAOXA films, most of them involved grafting of pre-synthesized adsorbates by exploiting functional anchors that are specific for the target substrate to passivate. In other works, the growth of a PAOXAbased film was triggered from the substrate itself, through surface-initiated CROP (SI-CROP), while interest has been rising in applying plasma polymerization of 2-oxazolines to generate robustly attached coatings on an array of different supports. Through these strategies, and with the general objective of suppressing nonspecific interaction with biological entities, a broad range of biomaterials, ranging from inorganic supports, plastics and nanomaterials of diverse composition have been successfully functionalized with PAOXAs. While during the first decade of 2000s efforts were spent in dissecting the fundamental properties of PAOXAs assemblies on surfaces, [3,10,11] during the past five years their application in different coating formulations for biomaterials has been progressively expanding, and at least some of them are probably mature for a direct involvement of industry. In this progress report, we critically review the most recent studies focusing on the fabrication of PAOXA coatings, especially concentrating on the generation of bioinert surfaces, which probably represents their most appealing and technologically relevant application. 2. Composition of Bioinert PAOXA-Based Surfaces Among the different PAOXA species that were applied on surfaces to generate coatings, hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) and poly(2-ethyl-2-oxazoline) (PEOXA) showed the most pronounced inertness towards nonspecific interactions with serum proteins, cells and bacteria. A recent study by Morgese et al. identified the superior biopassivity of linear Poly(2-alkyl-2-oxazoline)s (PAOXAs) are emerging among the most promising nonionic alternatives to poly(ethylene glycol)s (PEGs), specifically in the modification and functionalization of biomaterials. Due to their chemical tailorability and robustness, coupled to their relatively easy synthesis, PAOXAs are increasingly applied as adsorbates to generate bioinert surfaces that prevent nonspecific contamination by proteins, cells and bacteria. Passivation of medical devices, sensors and cell-sensitive platforms with PAOXAs enables a nearly quantitative suppression of nonspecific biological contamination, while biopassivity is maintained over longer incubation times than those recorded for more degradable PEG-b...

Block Length‐Dependent Protein Fouling on Poly(2‐oxazoline)‐Based Polymersomes: Influence on Macrophage Association and Circulation Behavior

“…To understand the mechanism of the protein antifouling properties of our polymersomes we employed a theoretical computational approach to studying the structure and dynamics of the polymer membranes and the associated interfacial surface water at all‐atom resolution. [ 29 ] Such an approach focusing on the interfacial ligand and water properties rather than simulating the actual protein binding to surfaces, has recently demonstrated the water structuring at the surface to be a good predictor of the ligand antifouling properties, at least on surfaces. [ 29 ] We constructed atomistic models of various PMOXA‐ b ‐PDMS‐ b ‐PMOXA membranes comprised of copolymers with the following relative polymer DP s: 1‐7‐1, 2‐13‐2, 3‐19‐3, 4‐25‐4, 5‐31‐5, 3‐37‐3, and 6‐37‐6 (Table 1, Figure , and Figures S8 and S9, Supporting Information).…”

“…[ 29 ] Such an approach focusing on the interfacial ligand and water properties rather than simulating the actual protein binding to surfaces, has recently demonstrated the water structuring at the surface to be a good predictor of the ligand antifouling properties, at least on surfaces. [ 29 ] We constructed atomistic models of various PMOXA‐ b ‐PDMS‐ b ‐PMOXA membranes comprised of copolymers with the following relative polymer DP s: 1‐7‐1, 2‐13‐2, 3‐19‐3, 4‐25‐4, 5‐31‐5, 3‐37‐3, and 6‐37‐6 (Table 1, Figure , and Figures S8 and S9, Supporting Information). Due to computational limitations, we simulated relatively small fragments of the membrane using model copolymer lengths corresponding to the shortest copolymers employed in the actual experiments described above, copolymer dispersity was not yet included (experimentally always > 1), and the simulations only provide limited information on conformation and dynamics of the ABA polymer chains within the membranes, which possibly include U‐ and I‐shape configurations in reality.…”

“…Our theoretical all‐atom simulations have shown that lower density PMOXA might be more efficient for the antifouling performance compared to PEG where density is less important. [ 29 ] In the non‐polymersome literature, antifouling behavior is commonly improved by using cyclic versus linear POx polymers, while extending the backbone monomer length using poly(2‐methyl‐2‐oxazine) (PMeOzi) to form more flexible polymers revealed even greater hydration and accompanied antifouling behavior than PMOXA and PEG. [ 27 ] Polymersome design, antifouling materials performance studies and simulations with further copolymer blends with even longer PMOXA chains, evaluating more complex architectures of POx, and polymersomes based on PMeOzi might be interesting future research avenues.…”

Dispersity within Brushes Plays a Major Role in Determining Their Interfacial Properties: The Case of Oligoxazoline-Based Graft Polymers

“…In order to investigate how the side-chain length and dispersity in the brush structure influence their interfacial properties, we concentrated on POEOXMA, as 2-oxazoline-based polymers represent some of the most promising replacements for PEG and its derivatives in biomaterials and biotechnology. − Precise tuning of graft polymer brush structure was achieved by first synthesizing OEOXMAs, which are intrinsically polydisperse, and subsequently purifying them into discrete macromonomers with distinct n by column chromatography. − …”

Atmospheric Pressure Plasma Polymerized 2-Ethyl-2-oxazoline Based Thin Films for Biomedical Purposes

“…Poly(2-oxazoline) (POx) is a promising alternative to polyethylene glycol (PEG) for polymer functionalization of surfaces which can impart desired biochemical properties to different materials [ 1 ]. POx has attracted substantial attention recently due to its antibiofouling properties [ 2 , 3 ] and good biocompatibility [ 4 ].…”