Mussel‐Inspired Adhesive Polydopamine‐Functionalized Hyaluronic Acid Hydrogel with Potential Bacterial Inhibition

Abstract

etc. Among them, hyaluronic acid (HA)derived hydrogel is one of the ideal candidates due to its inherent biological homology, feasible structure modification, as well as good degradability. [9,10] The high water retention capacity and high viscoelasticity of HA also allow it to be suitable for wound dressings.To construct desirable HA-based hydrogels, different strategies have been established. Relying on the intermolecular noncovalent interactions, the physical cross-linking HA hydrogels emerged. Rodell et al. developed a shearthinning and self-healing HA hydrogel due to the host-guest interaction between β-cyclodextrin (β-CD) and adamantine (AD) appended HA. [11] The hydrogel properties could be rationally tailored through the material concentration, degree of modification, and the ratio of β-CD to AD. Nevertheless, the physical hydrogels may exhibit undesirable mechanical properties and suffer from premature dissociation. Chemical crosslinking of pendant reactive groups by coordination chemistry or polymerization ignites an alternative route to fabricate HAbased hydrogels. In the meanwhile, transition metal ions or exogenous cross-linking agents usually involve, [12] which may impair the systemic biocompatibility due to their possible cytotoxicity. Recently, various compatible strategies have been proposed to develop biocompatible hydrogels, such as enzymemediated covalent linking, [13,14] disulfide cross-linking, [15,16] and Diels-Alder reaction. [17,18] Indeed, these chemical cross-linked hydrogels exhibit good mechanical property and are cytocompatible. However, their further applications are restricted by their limited functions. Thus, endowing HA hydrogels with multiple functions seems to be very promising, and fabricating HA-based functional hydrogels with good biocompatibility is still challengeable.In this study, a multifunctional hydrogel (PDA-HA) comprising of polydopamine (PDA) and thiolated hyaluronic acid (HA-SH) is developed (Scheme 1). PDA was introduced because of its good biocompatibility, strong tissue adhesion and effective free radical scavenging ability. Specially, it could act as the nanosized cross-linking agent that reacts with thiolated HA via Michael addition. The biocompatibility, gelling ability, tissue adhesion, free radical scavenging, and bacterial inhibition of the hybrid hydrogel were evaluated. The potential bacterial inhibition and good tissue adhesion endow the hydrogel with great potential for wound dressing.As shown in Figure 1A, thiolated hyaluronic acid (HA-SH) was obtained by two steps that referred to the amidation of Hyaluronic acid (HA)-based hydrogels have been receiving increasing attention for wound management. However, pure HA hydrogels usually exhibit weak mechanical strength and poor anti-infection. Herein, a hybrid HA-based hydrogel (PDA-HA) comprised of polydopamine (PDA) and thiolated hyaluronic acid (HA-SH) is developed based on the Michael addition reaction. The introduction of PDA into HA hydrogel can decrease the critical gel concentration, improve the c...

Mussel-inspired extracellular matrix-mimicking hydrogel scaffold with high cell affinity and immunomodulation ability for growth factor-free cartilage regeneration

“…This was because the PDA functionalization introduced abundant reactive catechol groups having high binding affinity to the diverse nucleophiles (e.g., amines, thiols, and imidazoles) of peptides and proteins on the cell surfaces. In the previous studies, PDA-modified HA was generally prepared based on EDC/NHS method [ 50 , 51 ] or thiol-prefunctionalized HA [ 52 , 53 ]. The efficiency of these chemical modifications is limited in terms of the low substitution of catechol groups and tedious preparation process, resulting in insufficient grafting ratio of catechol groups and a fast degradation rate of HA due to chain broken during grafting process.…”

Injectable multifunctional CMC/HA-DA hydrogel for repairing skin injury

“…They also synthesized HA-DA by EDC/NHS, and added polydopamine-coated reduction graphene oxide for hydrogels using the horseradish peroxidase (HRP)/hydrogen peroxide (H 2 O 2 ) system [ 27 ]. What's more, many other works also have shown that DA grafting onto hyaluronic acid molecules could enhance the adhesion ability of hydrogels [ [28] , [29] , [30] ].…”

“…Hydrogels prepared by physical methods usually have poor stability and are easy to degrade. The hydrogel prepared by chemical method has good mechanical properties, for example, the hydrogels prepared by dopamine and thiol hyaluronic acid through Michael addition reaction have good tissue adhesion in vitro, but the introduction of transition metal ions or exogenous coupling agents usually leads to cytotoxicity [ 31 ]. The enzymatic crosslinking method allows the reaction to be carried out under mild conditions.…”

Robust Hydrogel Adhesive with Dual Hydrogen Bond Networks

“…Inspired by the mussels’ biological events, several approaches have been followed to improve the hydrogel adhesion by optimizing the surface chemistry and hydrogel matrix. Biomimetic moieties containing catechol units [ 24 , 25 , 26 ], polydopamine [ 27 , 28 ], polyelectrolytes [ 8 , 29 , 30 ], and reactive chemical groups like N -hydroxysuccinimide (NHS) [ 31 , 32 ] were incorporated into the hydrogels to enhance adherence. Barrett et al reported that the hydrogel of PEO-PPO-PEO endcapped with catechols [ 33 , 34 ] adhered to hydrated tissue surfaces.…”