Engineered Poly (amino acid) Hydrogel Synchronizes Sequential Infection Elimination and Osteogenic Activation for...

Rationale: The treatment of infected bone defects is always a serious challenge in orthopedics. Infection control in the first stage followed by bone reconstruction in the second stage is the main clinical treatment process. The design of dual-functional materials with sequential antibacterial and bone-promoting properties according to the content and temporal characteristics of these two clinical tasks is a promising solution. Methods: In this study, the hydrogel composed of poly (ethylene glycol)-poly (L-alanine N-carboxyanhydride-co-L-phenylalanine N-carboxyanhydride) was constructed by ring-opening polymerization, and then its osteogenic and antibacterial properties were obtained by BMP-2 peptide grafting and vancomycin loading, respectively, and the engineered bifunctional hydrogel was constructed by combining these two functional hydrogels for sequential treatment of infected bone defects. A series of in vitro characterization experiments, biocompatibility analysis and evaluation of antibacterial and osteogenic properties were conducted. The specific therapeutic effect in vivo of constructed hydrogel was assessed using a model of infectious bone defect in the radius of rabbits. Results: Our results confirmed that the engineered hydrogel had the physicochemical properties suitable for clinical scenarios and rapid and sustained antibiotic release performance in the early stage, which resulted in significant inhibition of both Gram-positive and Gram-negative bacteria in vitro. Moreover, the hydrogel had appropriate cytocompatibility and demonstrated the ability to promote osteogenic differentiation of stem cells. By establishing an infected bone defect of radius in rabbit model, we confirmed that the hydrogel could accelerate the repair of infected bone defect by simultaneously achieving satisfactory infection control and bone reconstruction. Conclusions: This study provides a time-efficient single-stage strategy for the effective treatment of infected bone defects by constructing a dual-functional hydrogel with sequential antibacterial and osteogenic properties, which provides promising directions for future clinical treatment improvement.