Dynamically evolving piezoelectric nanocomposites for antibacterial and repair-promoting applications in infected wound healing

Wound healing from bacterial infections is one of the major challenges in the biomedical field. The tra-ditional single administration methods are usually accompanied with side effects or unsatisfactory effi-cacy. Herein, we design dynamically evolving antibacterial and repair-promoting nanocomposites (NCs) by in situ self-assembling of zeolitic imidazolate framework-8 (ZIF-8) on the surface of barium titanate (BTO), and further loading with a small amount of ciprofloxacin (CIP). The new strategy of combining pH-stimulated drug delivery and ultrasound-controlled sonodyamics has the potential to dynamically evolve in infected wound sites, offering a multifunctional therapy. In vitro study demonstrates that the enhance-ment generation of reactive oxygen species through the sonodynamic process due to the heterostructures and a small amount of CIP released in an acidic environment are synergistically antibacterial, and the inhibition rate was > 99.9%. In addition, reduced sonodynamic effect and Zn2 + generated along with the gradual degradation of ZIF-8 simultanously promote cell migration and tissue regeneration. The in vivo study of full-thickness skin wounds in mouse models demonstrate a healing rate of 99.3% could be achieved under the treatment of BTO@ZIF-8/CIP NCs. This work provides a useful improvement in ra-tional design of multi-stimulus-responsive nanomaterials for wound healing. Statement of significance A novel piezoelectric nanocomposite was proposed to realize sonodynamic therapy and pH-stimulated drug releasing simultaneously in wound healing treatment. The dynamically evolving structure of the piezoelectric nanocomposite in acidic microenvironment has been theoretically and experimentally veri-fied to contribute to a continuous variation of sonodymanic strength, which accompanied with the grad-ual releasing of drug and biocompatible Zn2+effectively balanced antibacterial and repair-promoting ef-fects. Both of the in vitro and in vivo study demonstrated that the strategy could significantly accelerate wound healing, inspiring researchers to optimize the design of multi-stimulus-responsive nanomaterials for various applications in biomedical and biomaterial fields. (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.