Mechano-Responsive, Tough, and Antibacterial Zwitterionic Hydrogels with Controllable Drug Release for Wound Healing Applications

Abstract

Acute wounds subject to frequent deformations are difficult to be treated because the healing process was easily interfered by external mechanical forces. Traditional wound dressings have limited efficacy because of their poor mechanical properties and skin adhesiveness and difficulty in the delivery of therapeutic drugs effectively. As such, tough and skin-adhesive wound dressings with sustainable and stimuli-responsive drug release properties for treatment of those wounds are highly desirable. For this purpose, we have developed a mechano-responsive poly­(sulfobetaine methacrylate) hydrogel which aims to control the delivery of antibiotic drug upon application of mechanical forces. Diacrylated Pluronic F127 micelles were used as a macro-cross-linker of the hydrogel and loaded with hydrophobic antimicrobial drugs. The micelle-cross-linked hydrogel has excellent mechanical properties, with the ultimate tensile strength and tensile strain of up to 112 kPa and 1420%, respectively, and compressive stress of up to 1.41 MPa. Adhesiveness of the hydrogel to the skin tissue was ∼6 kPa, and it did not decrease significantly after repetitive adhesion cycles. Protein adsorption on the hydrogel was significantly inhibited compared to that on commercial wound dressings. Because of the mechano-responsive deformation of micelles, the release of drug from the hydrogel could be precisely controlled by the extent and cycles of mechanical loading and unloading, endowing the hydrogel with superior antibacterial property against both Gram-positive and Gram-negative bacteria. In addition, drug penetration into the skin tissue was enhanced by mechanical stress applied to the hydrogel. The micelle-cross-linked zwitterionic hydrogel also showed good cell biocompatibility, negligible skin irritation, and healing capacity to acute skin wounds in mice. Such a tough mechano-responsive hydrogel holds great promise as wound dressings for acute wounds subjected to frequent movements.

Water‐Resistant Ionogel Electrode with Tailorable Mechanical Properties for Aquatic Ambulatory Physiological Signal Monitoring

“…[44,45] During the underwater adhesion of ionogels, the hydration layer on the substrate surface can be destroyed due to the hydrophobicity of the ionogels. Then, various interactions, such as ion-dipolar, [31,46,47] dipolar-dipolar, [48][49][50] metal complexation, [51] electrostatic, [44,52] cation-π interactions, [44] and van der Waals interactions, [53] can be formed between the ionogels and different substrates (Figure S8, Supporting Information). Therefore, underwater strong adhesion can be formed.…”

Highly Adhesive Antibacterial Bioactive Composite Hydrogels With Controllable Flexibility and Swelling as Wound Dressing for Full-Thickness Skin Healing

“…A skin irritation test was performed according to the reported method ( Fang et al, 2020 ; Ye et al). The back hair of the mice anesthetized by isoflurane was shaved and sterilized with betadine.…”

“…Moreover, these zwitterionic groups endow the hydrogels with effective antibacterial properties. However, owing to the high solvation of these zwitterionic groups, PolySBMA-based hydrogels mostly suffer from the limitation of large swelling and low bioactivity ( Fang et al, 2020 ; Ye et al, 2016 ; Wang Z. et al, 2020 ). Excessive swelling easily leads to the fluid unbalance of the ECM in vivo ( Ren et al, 2019 ).…”

Zwitterionic polymers in drug delivery: A review

“…An attempt was made by Fang et al to treat acute wounds via the application of zwitterionic sulfobetaine hydrogel. 110 Antimicrobial drugs loaded with diacrylate pluronic F127 micelle was prepared and cross-linked with poly(sulfobetaine methacrylate) hydrogel. Micelle cross-linked zwitterionic hydrogel was found to be biocompatible, negligible skin irritation property, and efficient acute skin wounds curing property in the mice model.…”