Ultrasound-triggered piezocatalytic composite hydrogels for promoting bacterial-infected wound healing

Dun Liu; Lei Li; Ben-Long Shi; Bo Shi; Ming-Ding Li; Yong Qiu; Di Zhao; Qun-Dong Shen; Ze-Zhang Zhu

doi:10.1016/j.bioactmat.2022.11.023

Ultrasound-triggered piezocatalytic composite hydrogels for promoting bacterial-infected wound healing

Bioact Mater. 2022 Dec 14:24:96-111. doi: 10.1016/j.bioactmat.2022.11.023. eCollection 2023 Jun.

Authors

Dun Liu¹, Lei Li², Ben-Long Shi¹, Bo Shi¹, Ming-Ding Li², Yong Qiu¹, Di Zhao³, Qun-Dong Shen², Ze-Zhang Zhu¹

Affiliations

¹ Division of Spine Surgery, Department of Orthopedic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
² Department of Polymer Science and Engineering, Key Laboratory of High-Performance Polymer Materials and Technology of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
³ Institute of Brain Science and Disease, School of Basic Medicine, Qingdao University, Qingdao, Shandong, 266001, China.

Abstract

Wound healing has become one of the basic issues faced by the medical community because of the susceptibility of skin wounds to bacterial infection. As such, it is highly desired to design a nanocomposite hydrogel with excellent antibacterial activity to achieve high wound closure effectiveness. Here, based on ultrasound-triggered piezocatalytic therapy, a multifunctional hydrogel is designed to promote bacteria-infected wound healing. Under ultrasonic vibration, the surface of barium titanate (BaTiO₃, BT) nanoparticles embedded in the hydrogel rapidly generate reactive oxygen species (ROS) owing to the established strong built-in electric field, endowing the hydrogel with superior antibacterial efficacy. This modality shows intriguing advantages over conventional photodynamic therapy, such as prominent soft tissue penetration ability and the avoidance of serious skin phototoxicity after systemic administration of photosensitizers. Moreover, the hydrogel based on N-[tris(hydroxymethyl)methyl]acrylamide (THM), N-(3-aminopropyl)methacrylamide hydrochloride (APMH) and oxidized hyaluronic acid (OHA) exhibits outstanding self-healing and bioadhesive properties able to accelerate full-thickness skin wound healing. Notably, compared with the widely reported mussel-inspired adhesive hydrogels, OHA/THM-APMH hydrogel due to the multiple hydrogen bonds from unique tri-hydroxyl structure overcomes the shortage that catechol groups are easily oxidized, giving it long-term and repeatable adhesion performance. Importantly, this hybrid hydrogel confines BT nanoparticles to wound area and locally induced piezoelectric catalysis under ultrasound to eradicate bacteria, markedly improving the therapeutic biosafety and exhibits great potential for harmless treatment of bacteria-infected tissues.

Keywords: APMH, N-(3-aminopropyl)methacrylamide Hydrochloride; Antibacterial ability; BT, Barium Titanate; Bioadhesiveness; Multifunctional hydrogels; OHA, Oxidized Hyaluronic Acid; Piezocatalytic therapy; ROS, Reactive Oxygen Species; SDT, Sonodynamic therapy; Self-healing; THM, N-[tris(hydroxymethyl)methyl]acrylamide; US, Ultrasound.