Highly improved aqueous lubrication of polymer surface by noncovalently bonding hyaluronic acid-based hydration layer for endotracheal intubation

Abstract

Hydration lubrication is the key responsible for the exceptionally low boundary friction between biosurfaces. However, it is a challenge to settle a hydration layer on a polymer surface via a noncovalent manner. Herein, we develop a highly lubricated coating absorbed onto the polymer surface via intermolecular association of hyaluronic acid (HA)-based micelles. A poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (Pluronic, F127) is recruited to complex with HA and further self-assembled to form a thick micelle layer. High water-retaining capacity of the HA/F127 coating enables the decorated surface with excellent hydrophilicity and boundary lubrication, where the coefficient of friction in aqueous media is reduced by 60% compared with the bare polymer surface. The HA/F127 coating suppresses nonspecific protein adsorption and exhibits good biocompatibility. More remarkably, an in vivo cynomolgus monkey model, demonstrates the utility of the HA/F127 coating in alleviating or preventing complications of endotracheal intubation, such as foreign irritation, airway mucosal damage, and inflammatory response. This cost-effective and scalable approach is suitable to manufacture interventional devices especially disposable medical devices with highly lubricated surface.

Introduction

Aqueous lubrication exists ubiquitously in many anatomical parts of organisms including the respiratory tract [[1], [2], [3]], articular cartilage [[4], [5], [6], [7]], visceral organs [8,9], and ocular surfaces [[10], [11], [12]]. Good lubrication with low-friction movement is important to maintain the normal physiological functions of human body [[13], [14], [15]]. Therefore, the low boundary friction against tissues is at a premium for the application of medical devices that, however, usually do not have the ability of biointerfacial lubrication [[16], [17], [18], [19], [20]]. One representative example is endotracheal intubation, a very common clinical intervention to secure the airway, to maintain unobstructed breath, and to manage inhalation anesthetics. A paucity of aqueous lubrication of the tube results in many side effects, including not only mucosal damage and laryngeal edema to distress patient comfort [21], but also tracheal stenosis with a high risk to threaten the patient's life [22,23].

As per current understanding, the formation of a hydration layer on the underlying substrate, is considered as aqueous lubrication [[24], [25], [26]]. Confined water in the hydration layer serves as an eminent lubricant between sliding surfaces [27]. The lubrication performance is particularly pertinent to the water stabilization in the confined regime due to its low viscosity. Several approaches have been advanced to create a hydration layer on sliding materials by covalently bonding the molecules with hydrophilic groups [[28], [29], [30]]. A number of diblock copolymers with different lubricating blocks were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization [31]. A large reduction in the coefficient of friction (CoF) was observed in the polymer with quaternary amine cartilage-binding blocks. A poly(2‐methacryloyloxyethyl phosphorylcholine) (pMPC) brush was covalently bonded on the pretreated mica surface through atom transfer radical polymerization (ATRP) [32]. The coating showed a low CoF of 10⁻³, due to the highly hydrated nature of hydrophilic polymer brushes. A diamond-like carbon (DLC) film was prepared by surface initiated ATRP to simulate the biological lubrication of articular cartilage [33]. Macroscopic tribological properties revealed a low CoF (0.0062) in water sliding. Nevertheless, the chemical motif may compromise its applicability with regard to disposable medical consumables due to complicated procedures, low production efficiency, and exorbitant cost.

In this scenario, the physical motif is preferred to achieve hydration lubrication by tenaciously attaching hydrated polymers on the rubbing surface in an aqueous medium. Hyaluronic acid (HA), a naturally linear polysaccharide, is a primary ingredient in connective tissues and the surrounding synovial fluid [34]. The disaccharide units (namely glucuronic acid and N-acetylglucosamine) of HA can stabilize water molecules, thus making it a preferably biomimetic lubricant. In addition, HA is nonimmunogenic, biodegradable, and biocompatible [35,36]. These traits facilitate the application of HA in various fields, such as articular cartilage, ophthalmic viscosurgery, and tissue engineering [[37], [38], [39]]. However, it is a daunting challenge to attach HA on the polymer surface due to the absence of adhesive or cohesive properties. The efficiency of HA as a biointerfacial lubricant is thus largely restricted.

Herein, we developed a highly lubricated coating on the polymer surface via the intermolecular association of HA-based micelles [40]. A poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (Pluronic, F127) was used to complex with HA. The amphiphilic property of F127 can bind with HA and drive the self-assembly on the polymer surface to form a strong lubricating boundary layer. The advantages of our lubricated coating were demonstrated in terms of water contact angle (WCA), CoF, surface abrasion, and protein adsorption. Particular interests were gained on restraining mucosal damage and inflammation during trachea intubation, which was verified via a cynomolgus monkey model.