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Published on: June 7, 2024
Hyaluronic acid-based hydrogel microspheres with multi-responsive properties for antibacterial therapy and bone
Xiaolong Lin1, Shuli Deng1, Tao Fu2
1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.
Abstract:
This study introduces hyaluronic acid-based (HA) hydrogel microspheres loaded with zinc oxide nanoparticles (ZnO-NPs) for the treatment of infectious bone defects. The microspheres were fabricated using a 3D-printing process, with a formulation consisting of 6 wt% HAD (methacrylated HA), 3 wt% AOHA (AMP-conjugated oxidized HA), 1 % BOHA (phenylboric acid-conjugated HA), 0.5 % photoinitiator, and 0.05 % ZnO-NPs. In vitro, the hydrogel microspheres demonstrated significant antibacterial activity against Staphylococcus aureus, with colony counts and biofilm inhibition assays showing a marked reduction in bacterial growth after 12 and 24 h. The release of antimicrobial peptides (AMPs) was enhanced in acidic conditions and in the presence of hyaluronidase. The microspheres also promoted osteogenic differentiation of bone marrow stromal cells (BMSCs), as evidenced by increased expression of osteogenic markers (ALP, OCN, OPN, and COL-1). In vivo, the hydrogel microspheres were tested in a rat skull defect model, showing significant bone regeneration, improved angiogenesis, and an anti-inflammatory response. These results indicate that ABOHA@ZnO hydrogel microspheres provide a promising strategy for treating infectious bone defects by combining antimicrobial, osteogenic.
