Nanoclay Hydrogel Microspheres with a Sandwich‐Like Structure for Complex Tissue Infection Treatment

Addressing complex tissue infections remains a challenging task because of the lack of effective means, and the limitations of traditional bioantimicrobial materials in single‐application scenarios hinder their utility for complex infection sites. Hence, the development of a bioantimicrobial material with broad applicability and potent bactericidal activity is necessary to treat such infections. In this study, a layered lithium magnesium silicate nanoclay (LMS) is used to construct a nanobactericidal platform. This platform exhibits a sandwich‐like structure, which is achieved through copper ion modification using a dopamine‐mediated metallophenolic network. Moreover, the nanoclay is encapsulated within gelatin methacryloyl (GelMA) hydrogel microspheres for the treatment of complex tissue infections. The results demonstrate that the sandwich‐like micro‐ and nanobactericidal hydrogel microspheres effectively eradicated Staphylococcus aureus (S. aureus) while exhibiting excellent biocompatibility with bone marrow‐derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Furthermore, the hydrogel microspheres upregulated the expression levels of osteogenic differentiation and angiogenesis‐related genes in these cells. In vivo experiments validated the efficacy of sandwich‐like micro‐ and nanobactericidal hydrogel microspheres when injected into deep infected tissues, effectively eliminating bacteria and promoting robust vascular regeneration and tissue repair. Therefore, these innovative sandwich‐like micro‐ and nanobacteriostatic hydrogel microspheres show great potential for treating complex tissue infections. The injectable nanoclay hydrogel with a sandwich‐like structure microspheres enable a controlled release of metal ions, which synergistically eradicate bacteria in deep tissues and facilitate tissue regeneration. This micro‐nano system surpasses the limitations associated with conventional biological antibacterial materials. It demonstrates broad applicability and robust bactericidal efficacy, representing a significant advancement in the field of antibacterial therapies.