Adsorbent of bacteria and inflammatory Factors: Injectable dual-network hydrogel for osteomyelitis treatment.

Abstract

Current treatments for osteomyelitis are often hampered by biofilm formation, the emergence of multidrug-resistant (MDR) bacteria, and limited antibiotic penetration into infected bone tissue, all of which impede bone regeneration and prolong the disease progression. Herein, based on the chlorogenic acid (CA)-Mg²⁺ coordination and covalent crosslinking of genipin (GP) with proteins, we proposed an injectable dual-network natural hydrogel named as CA-Mg/BSA-GP (CMBG) hydrogel. GP functions as a biological crosslinker, facilitating the adsorption and crosslinking exogenous bovine serum albumin (BSA) and polypeptide antibiotics, as well as endogenous inflammatory factors and bacterial surface proteins within the infection microenvironment. The CMBG hydrogel doped with polypeptide antibiotics (vancomycin and polymyxin B) effectively eradicates MDR strains (MRSA RJ011 and Escherichia coli RJ054) through the synergistic effect of CA and antibiotics. Additionally, CA released from the CA-Mg network, combined with the crosslinking of inflammatory factors and bacterial proteins, effectively inhibits inflammation and reduces local oxidative stress. Finally, the anti-infective environment, together with the bioactive release of CA and Mg²⁺, upregulates osteogenic protein expression and promotes bone repair. Collectively, the polypeptide antibiotics-doped CMBG hydrogel demonstrates potent antibacterial, anti-inflammatory, and osteogenic properties, offering a promising minimally invasive therapeutic strategy for MDR bacteria-associated osteomyelitis.