Biomimetic nanocomposite hydrogel networks for robust wet adhesion to tissues

Abstract

Designing multifunctional medical adhesives with strong adhesiveness under water is of great significance to achieve desirable therapeutic effects for promoting wound healing. However, its design is still challenging since most of existing hydrogel adhesive cannot work in wet environments. Here we proposed a tissue adhesive made from a combination of hydrogel matrix and nanocrystal fillers. The adhesion mechanism of this hydrogel adhesive relies on the absorption of interfacial water from tissue surfaces by hydrophilic hydrogel matrix, while the nanocrystals from the hydration process of calcium sulphoaluminate (CSA) contributes to strong cohesion. Subsequent noncovalent and covalent bonds between amine groups on tissue surfaces and catechol groups on polydopamine-intercalated silicate nanoflakes (PDA-Silicate) further improves the adhesion ability. The hydrogel adhesive with optimal compositions exhibited robust adhesiveness to different surfaces, with over 30 kPa of adhesive strength to porcine skin under water. Furthermore, chopped curcumin-loaded electrospun nanofibers were added into the precursor with optimized formulation to form nanofibers/hydrogel composite (NF-HG) in situ. The obtained NF-HG exhibited enhanced antibacterial activity, sustained drug release and good cytocompatibility. Taken together, this strategy may open new route to design versatile functional underwater adhesives.

Introduction

Adhesives have received considerable attention in biomedical industry, such as wound sealants, hemostatic agents and tissue adhesives [[1], [2], [3], [4]]. Since adhesives are able to bond with biological tissues immediately, preventing blood leakage and accelerating wound closure [5]. Strong interaction with contacting surfaces is the prerequisite for biomedical adhesives [6,7]. However, some of current available bioadhesives, such as fibrin and cyanoacrylate, are far to satisfy the medical demand due to their low biocompatibility and poor adhesion to wet or bleeding tissues [8,9]. As water forms a boundary layer that separates molecules from two surfaces, leading to adhesion failure [10].

In nature, marine mussels and sandcastle worms can adhere to various surfaces and keep strong adhesion under seawater [11,12]. 3,4-Dihydroxy-_l-phenylalanine (DOPA), a catechol-containing polymer existed in their adhesive proteins, has been proved to play crucial roles in water-resistant adhesion [13]. By mimicking the chemical composition of mussel foot proteins, amounts of catechol-containing hydrogels were prepared as biological adhesives. However, they usually exhibited excellent dry adhesiveness but adhesion disappeared in the presence of water [14,15]. Recently, it has been proposed that removing interfacial water from contacted surfaces is the secret for mussel adhesion in wet environments [16,17]. Inspired by this adhesion mechanism, Yuk et al. [18] adopted a dry-crosslinking mechanism to remove interfacial water from contacted surfaces, forming robust adhesion on wet tissues. Fan et al. [19] introduced hydrophobic moieties into hydrogel to repel interfacial water and achieved good wet adhesion. However, the preparation of these hydrogels is energy-consuming due to the use of UV or thermal activation. Besides, the hydrophobicity of hydrogel is not conducive to wound healing [20]. Hence, there is still an unmet need for fabricating biocompatible adhesives with excellent wet adhesion using a facile method.

Herein, we aimed to synthesize a biomimetic underwater adhesive that rendered strong interaction and energy-saving process. We have previously found that the narrow space between silicate nanoflake was similar with the confined nanospace of mussel byssal thread, which could prevent the over-oxidation of polydopamine (PDA) and preserve abundant catechol groups for adhesion [21]. In this study, hydrogel adhesives were prepared by simple blending of acrylic amide (AM), PDA-Silicate, calcium sulphoaluminate (CSA) and nano-reinforcement cellulose nanocrystals (CNC) under ambient environment. The hydrophilic polyacrylamide (PAM) can squeeze out the interfacial water by swelling. Meanwhile, the fast hydration process of CSA would generate nanocrystals for polymer crosslinking and accelerate the hydrogel solidification, contributing to strong wet adhesiveness. The mechanical property and adhesive performance were investigated to determine the optimal mass of CNC and CSA in the hydrogel network, respectively. Furthermore, the hydrogel adhesives with antibacterial ability and sustained drug release would be beneficial for wound closure [[22], [23], [24]]. Thus, chopped curcumin (Cur)-loaded electrospun nanofibers (NF) were added into the pre-gel solution with optimal content of CNC and CSA to form nanofibers/hydrogel composite (NF-HG) in situ. The prepared NF-HG is expected to exhibit good stretchability, robust underwater adhesiveness, sustained drug release, excellent anti-infection ability and good cell compatibility. To the best of our knowledge, such a multifunctional hydrogel adhesive is first reported in this work. The desirable properties coupled with a simple fabricating process indicated that the hydrogel could be an attractive material for biomedical applications, and this strategy may shed new light on the development of multifunctional hydrogel adhesives.