Injectable Antimicrobial Quaternary Chitosan Salt/Tannic Acid as a Delivery Platform for Enhanced Cranial Bone Regeneration via the Synergy of BMP-2 and VEGF

Treating large, irregularly shaped bone defects continues to be a major challenge in clinical practice. In this work, an innovative injectable antimicrobial delivery platform is introduced. The therapeutic system leverages the combination of quaternary chitosan salt (QCS) and tannic acid (TA), synergistically supplemented with BMP-2 and VEGF, to enhance the regenerative efficacy. Hydrogen bonding between QCS and TA enhances mechanical strength, while the localized delivery of BMP-2 and VEGF promotes osteogenesis and angiogenesis. The sustained antimicrobial activity of QCS/TA further supports a regenerative microenvironment. Mechanistic analysis showed upregulated osteogenic gene expression in the QCS/TA/BMP-2/VEGF group, consistent with in vivo results─nearly 80% defect closure within 8 weeks. The injectable QCS/TA hydrogel platform incorporated with BMP-2 and VEGF represents a promising strategy for repairing bone defects, emphasizing its pioneering role in addressing clinical challenges.