MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds

Abstract

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopaminefunctionalized oxidized hyaluronic acid/carboxymethyl chitosan/ collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N−Ag−N bond between CCS and Ag ions, and the S−Ag−S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

Multifunctional Self-Healing Carbon Dot–Gelatin Bioadhesive: Improved Tissue Adhesion with Simultaneous Drug Delivery, Optical Tracking, and Photoactivated Sterilization

“…However, the bioadhesive revealed an increase in adhesive strength of 0.58 MPa, demonstrating its superior quality as a wound sealant (Figure D,E). This achievement of superior adhesive strength is noteworthy when compared to other bioadhesives reported in the literature that range between 0.06 and 0.18 MPa. − …”

Advancements and Challenges in Self-Healing Hydrogels for Wound Care

“…Innovative crosslinking techniques [9,16,70,71] are being investigated to enhance hydrogels' physical properties, such as durability, flexibility, and self-healing capabilities. The extensive research into chitosan derivatives [18,19,21,24,29,[31][32][33][34][72][73][74][75][76][77][78][79] showcases the ongoing efforts to improve its biomedical applications. Moreover, the exploration of hydrogels featuring novel materials and crosslinking methods [17,23,27,28,30,[39][40][41][80][81][82][83][84] reflects a commitment to innovation in developing more effective, responsive, and specialized systems.…”

“…By incorporating modifications such as silver nanoparticles or Fe 3+ ions [34,37,38,56], these hydrogels not only gain antimicrobial properties but also experience an enhancement in the robustness of their network. Additionally, the incorporation of Schiff bases, along with hydrogen bonds and ionic interactions [12,47,58,77,[88][89][90][91][92][93][94][95], serves to amplify their mechanical properties and responsiveness. Enzymatic crosslinking, particularly through the use of horseradish peroxidase [96], fosters the development of complex structures within the hydrogel, significantly enhancing both its strength and its self-healing capacities.…”

“…Hybrid crosslinking systems have introduced innovations like MMP-responsive nanoparticle-loaded injectable adhesive self-healing hydrogels, composed of dopaminefunctionalized oxidized hyaluronic acid, carboxymethyl chitosan, and collagen. These hydrogels stand out for their injectability, self-healing, tissue adhesion, and biocompatibility, promoting wound healing through controlled curcumin release [77]. Another injectable, self-healing antioxidant hydrogel combines collagen, hyaluronic acid, gallic acid, dopamine, and gamma-poly(glutamic acid) with 3-aminophenylboric acid via dynamic boronic ester bonds, thereby enhancing wound repair [83].…”

Dual-Modified Hyaluronic Acid for Tunable Double Cross-Linked Hydrogel Adhesives

“…(1) A system that creates mechanical interlocks and physical entanglements with the tissue surface; these materials are often cross-linked by free radical polymerization. , (2) The formational of covalent bonds between adhesive and tissue, through modification of the adhesive with a chemical binding site, wherein catechol and aldehyde modifications are the most prevalent methods. ,,− However, catechol functionality is susceptible to oxidation, which poses challenges to adhesive performance . Recently, biopolymer-based hydrogels with aldehyde modification have been successfully developed and demonstrated excellent adhesive performance. − Sigen et al designed an adhesive and injectable hydrogel composed of aldehyde-modified HA and a disulfide cross-linker 3,3′-dithiobis (propionic hydrazide) (DTPH), which showed excellent adhesive capabilities by outperforming bovine serum albumin-glutaraldehyde (BSAG) glue by 65.8% during a lap-shear study with enhanced biocompatibility . However, the use of aldehyde-modified biopolymers for enhanced adhesive properties often leads to a conflict between injectability and stability .…”