Directional Freeze‐Casting Cryogel Loaded with Quaternized Chitosan Modified Gallium Metal–Organic Frameworks to Capture and Eradicate the Resistant Bacteria for Guided Regeneration in Infected Bone Defects

Antimicrobial resistance and impaired bone regeneration are the great challenges in treating infected bone defects. Its recurrent and resistant nature, high incidence rate, long-term hospitalization, and high medical costs have driven the efforts of the scientific community to develop new therapies to improve the situation. Considering the complex microenvironment and persistent mechanisms mediated by resistant bacteria, it is crucial to develop an implant with enhanced osseointegration and sustained and effective infection clearance effects. Here, a positively charged quaternized chitosan (QCS) coated gallium-based metal-organic framework (GaMOF) is designed, to capture the antibiotic-resistant bacteria (Methicillin-resistant Staphylococcus aureus, MRSA) as a "captor", and rejuvenate Methicillin (Me) via disturbing the tricarboxylic acid (TCA) cycle. Then, a radially oriented porous cryogel loaded with the Me and QCSGaMOF is fabricated by the directional freeze-casting method. The oriented porous structure has an enhanced osseointegration effect by guiding the ingrowth of osteogenic cells. In vitro and in vivo experiments prove the advantages of as-prepared Me/QCSGa-MOF@Cryogel in combating resistant bacteria and guiding bone regeneration in infected bone defects.