Injectable Intrinsic Photothermal Hydrogel Bioadhesive with On‐Demand Removability for Wound Closure and MRSA‐Infected Wound Healing

Abstract

Photothermal hydrogel adhesives have yielded promising results for wound closure and infected wound treatment in recent years. However, photothermal hydrogel bioadhesives with on-demand removability without additional nanomaterials-based photothermal agents have rarely been reported in the literature. In this work, an injectable intrinsic photothermal hydrogel bioadhesive with an on-demand removal trait is developed through dynamic cross-linking of gelatin (Gel), tannic acid (TA) quinone, and borax for closing skin incisions and accelerating methicillin-resistant Staphylococcus aureus (MRSA) infected wound healing. The TA quinone containing polyphenol and quinone groups with multifunctional adhesiveness and intrinsic photothermal performance confer the hydrogel adhesive with near-infrared (NIR) responsive antibacterial activity. The cross-linking of pH-sensitive boronic ester (polyphenol−B) and Schiff base bonds endow the hydrogel with great self-healing capacity and on-demand removability. Moreover, the hydrogel possesses good biocompatibility, injectability, and hemostasis. The in vivo experiment in a rat cutaneous incision model and full-thickness MRSA-infected wound model indicate that the smart hydrogel can close wounds efficiently and treat infected ones, demonstrating its superiority in noninvasive treatment of cutaneous incisions and enhancing infected full-thickness wound healing.

Polyphenolic Gelatin-Based Bioadhesives

“…25 A recent report proposed incorporation of oxidized TA into gelatin solutions followed by cross-linking using borax (Figure 2A). 33 The hydrogels adhered to various tissue types (adhesion strength of up to ∼100 kPa), which improved further with increasing TA content (Figure 2B,C). Bioadhesion in these hydrogels was found to be pH-responsive, where increased acidity triggered hydrogel dissociation and aided in controllable deactivation of bioadhesion (Figure 2D).…”

“…(D) Responsiveness of adhesion to pH. Reproduced with permission from ref . Copyright 2023 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…Tannic acid (TA) is the most commonly used tannin for bioadhesion, which can be incorporated in hydrogels noncovalently because they have no functional groups in their structure for nucleophilic conjugation to biomaterials. 33 Tannic acids form strong chemical complexes with proteins and metal ions. Lignin is another similarly structured molecule used to introduce bioadhesion and is mostly integrated physically with the hydrogel networks.…”

Bioadhesives with Antimicrobial Properties

“…[ 153 ] It was demonstrated that NIR irradiation induced a highly effective antimicrobial activity in vitro and in vivo. [ 154 ]…”

Andrias Davidianus Mucus-Based Bioadhesive with Enhanced Adhesion and Wound Healing Properties

“…Fibrin glue, another common commercial bioadhesive, shows good biocompatibility and can maintain a soft wound, but its adhesive strength is low and often needs to be used with sutures . In addition, many underinvestigated hydrogel-based bioadhesives are potentially useful as alternatives. − For example, Ke et al utilized natural macromolecular silk fibroin to spontaneously coassemble with a natural plant polyphenol, tannic acid, and iron oxide nanoparticles (Fe 3 O 4 NPs) to construct a silk fibroin-based bioadhesive. The produced bioadhesives are flexible, highly extensible, and self-healing, and they show considerable wet adhesion ability and biocompatibility .…”