The management of chronic infected wounds poses significant challenges due to frequent bacterial infections, high concentrations of reactive oxygen species, abnormal immune regulation, and impaired angiogenesis. This study introduces a novel, microenvironment-responsive, dual dynamic, and covalently bonded hydrogel, termed OHA-P-TA/G/Mg2+. It is derived from the reaction of Tannic acid (TA) with Phenylboronic acids (PBA), which are grafted onto oxidized hyaluronic acid (OHA-P-TA), combined with GelMA (G) via Schiff base and chemical bonds, and incorporates Mg2+. This hydrogel exhibits pH and ROS dual-responsiveness, demonstrating effective antibacterial capacity, antioxidant ability, and the initiation of inflammation under distinct acidic and oxidative microenvironments. Furthermore, the release of Mg2+ from the TA-Mg2+ network (TA@Mg2+) promotes the transformation of pro-inflammatory M1 phenotype macrophages to anti-inflammatory M2 phenotype, showing a microenvironment-responsive response. Finally, in vivo results indicate that the OHA-P-TA/G/Mg2+ hydrogel enhances epithelial regeneration, collagen deposition, and neovascularization, showing great potential as an effective dressing for infected wound repair.
The devastating occurrence of drug resistance such as antimicrobial resistance has aroused global concerns for public health, which has propelled a continuous pursuit of safe and effective therapeutic agents. In this study, silver nanoparticles were decorated in mesoporous silica of SBA-15 coated with melanin-like polydopamine (PDA) as nanocarriers. Meanwhile, the constructed mesopore was loaded with phytochemical curcumin (CCM) through its noncovalent interactions with PDA coatings. The obtained CCM@SBA-15/PDA/Ag composites were characterized by physicochemical methods and exhibited desirable biocompatibility and low hemolytic activity. The dual-stimuli-responsive (pH and ROS) release of curcumin and/or silver nanoparticles from the CCM@SBA-15/PDA/Ag composites was achieved to reduce the side effects of noncontrolled drug leakage under physiological conditions. Additionally, compared with that of SBA-15/PDA/Ag and CCM@SBA-15/PDA, CCM@SBA-15/PDA/Ag combination showed a prolonged inhibitory effect on bacterial growth of G–E. coli (72 h) and G+S. aureus (24 h), attributing to the enhanced effect of the bactericide of silver nanoparticles and curcumin. Furthermore, through the utilization of the nanoformulation of curcumin, improved chemotherapeutic efficiency against human cervical cancer cells (HeLa) and Taxol-resistant nonsmall cell lung cells (A549/TAX) was identified in comparison with that of free curcumin. Thus, our study rationalized the combinational design of the natural compound and silver nanoparticles as an integrated dual-responsive nanoplatform in dealing with infectious bacteria and drug resistance in cancers for enhanced therapy.