Antisense yycF and BMP-2 co-delivery gelatin methacryloyl and carboxymethyl chitosan hydrogel composite for infective bone defects regeneration

Repairing infected bone defects remains a challenge in clinical work. Intractable bacterial infections and insufficient osseointegration are major concerns for infected bone defects. To address these issues, we developed a gelatin methacryloyl (GelMA) and carboxymethyl chitosan (CMCS) composite hydrogel with BMP-2 growth factor and GO based antisense technology supported by a PLGA spring. In vitro, photo-crosslinked GelMA composite hydrogels shown excellent biocompatibility and degradability. Relying on the release of BMP-2 from the composite hydrogel provides osteogenic effects. The antisense yycF and BMP-2 were released with the degradation of GelMA and CMCS composite hydrogel. In terms of antimicrobial properties, CMCS, GO and post transcriptional regulatory antisense yycF from the composite hydrogel synergistically kill S. aureus. In vivo, we implanted the composite hydrogel in a rat model of S. aureus infected femur defect, effectively accelerating bone healing in an infectious microenvironment. This research provides a novel biomaterial that is both antimicrobial and promotes bone regeneration, with the potential to treat infected bone defects.