Reducing Protein Adsorption with Polymer-Grafted Hyaluronic Acid Coatings

Abstract

We report a thermoresponsive chemical modification strategy of hyaluronic acid (HA) for coating onto a broad range of biomaterials without relying on chemical functionalization of the surface. Poly(di(ethylene glycol) methyl ether methacrylate) (PMEO2MA), a polymer with a lower critical solution temperature of 26 °C in water, was grafted onto HA to allow facile formation of biopolymer coatings. While the mechanism for film formation appears to involve a complex combination of homogeneous nucleation followed by heterogeneous film growth, we demonstrate that it resulted in hydrophilic coatings that significantly reduce protein adsorption despite the high fraction of hydrophobic (PMEO2MA). Structural characterization was performed using atomic force microscopy (AFM), which showed the formation of a dense, continuous coating based on 200 nm domains that were stable in protein solutions for at least 15 days. The coatings had a water contact angle of 16°, suggesting the formation of hydrophilic but not fully wetting films. Quartz crystal microbalance with dissipation monitoring (QCM-D) as well as biolayer interferometry (BLI) techniques were used to measure adsorption of bovine serum albumin (BSA), fibrinogen (Fbg), and human immunoglobulin (IgG), with results indicating that HA-PMEO2MA-coated surfaces effectively inhibited adsorption of all three serum proteins. These results are consistent with previous studies demonstrating that this degree of hydrophilicity is sufficient to generate an effectively nonfouling surface and suggest that segregation during the solubility transition resulted in a surface that presented the hydrophilic HA component of the hybrid biopolymer. We conclude that PMEO2MA-grafted HA is a versatile platform for the passivation of hydrophobic biomaterial surfaces without need for substrate functionalization.

Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques

“…In another study, and to improve the antibacterial activity, mechanical property, and the denaturation temperature, assimilation of synthesized Ag–pectin NPs in a self‐assembly process of collagen was performed . The adsorption of protein onto the surface of scaffolds can be modulated by modifying with NPs and other surface active agents . Based on this concept, Yassin et al designed a copolymer poly( l ‐lactide‐ co ‐ε‐caprolactone) scaffold functionalized with nanodiamond particles by a vacuum technique for bone regeneration.…”

A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration

“…[3,[5][6][7][8] Adsorption of serum proteins onto the surfaces of implanted scaffolds initiates a cascade of biological events that can lead to deleterious host responses, often resulting in formation of a fibrous capsule or the development of chronic inflammation. [9] One approach to inhibiting protein adsorption is to increase the hydrophilicity of the surface of the scaffold. [9,10] It is hypothesized that scaffolding that has protein-resistant surfaces would enhance biocompatibility by inhibiting protein adhesion.…”

“…[9] One approach to inhibiting protein adsorption is to increase the hydrophilicity of the surface of the scaffold. [9,10] It is hypothesized that scaffolding that has protein-resistant surfaces would enhance biocompatibility by inhibiting protein adhesion. [11] Aliphatic polyester scaffolds tend to be hydrophobic, and this might not favor cellular attachment and differentiation.…”

Recent Strategies to Develop Polysaccharide‐Based Nanomaterials for Biomedical Applications

“…Facile coupling reactions have also been reported to synthesize amphiphilic polysaccharides. Typical examples include HA‐ g ‐PLGA in the presence of dicyclohexyl carbodiimide, CD grafted with PEO‐ b ‐PCL in the presence of N,N ‐carbonyl diimidazole (CDI), β‐CD grafted with PCL‐ b ‐PEO‐ b ‐PCL triblock copolymer, and HA grafted with a thermoresponsive polymer . Recently, PCL was grafted to HA through a carbodiimide coupling reaction to form PCL–HA, which self‐assembled to form anionic micelles in physiological conditions.…”

“…Typical examples include HA-g -PLGA in the presence of dicyclohexyl carbodiimide, [ 56 ] CD grafted with PEO-b -PCL in the presence of N,N -carbonyl diimidazole (CDI), [ 57 ] β-CD grafted with PCL-b -PEO-b -PCL triblock copolymer, [ 58 ] and HA grafted with a thermoresponsive polymer. [ 59 ] Recently, PCL was grafted to HA through a carbodiimide coupling reaction to form PCL-HA, which self-assembled to form anionic micelles in physiological conditions. The anionic HA coronas were ionically interacted with cationic CS to form CS/PCL-HA polyelectrolyte complex aggregates for oral drug delivery.…”