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

Abstract

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.