Injectable hydrogels for osteomyelitis treatment induce metabolic reprogramming for protection against reinfection

Area of Science:

• Biomaterials Science
• Immunology
• Infectious Diseases

Background:

• Osteomyelitis, particularly multidrug-resistant strains, presents significant clinical challenges.
• Current treatments face limitations due to recurrent infections and antibiotic resistance.

Purpose of the Study:

• To develop an injectable hydrogel for simultaneous pathogen eradication, innate immune memory induction, and bone regeneration in osteomyelitis.
• To investigate the immunomodulatory and bone repair capabilities of the hydrogel in situ.

Main Methods:

• An injectable GaCuVanHACHO-BSA hydrogel was designed for self-assembly within the bone marrow cavity.
• The hydrogel's capacity to capture pathogens and inflammatory mediators was assessed.
• Mechanisms of trained immunity induction, including metabolic reprogramming and cytokine production, were analyzed.
• Bone regeneration and immune modulation effects of glycyrrhizic acid were evaluated.

Main Results:

• The hydrogel demonstrated effective pathogen capture, enhanced biocompatibility, and sustained antigen release.
• In situ activation of pattern recognition receptors led to metabolic reprogramming and amplified inflammation, inducing trained immunity.
• The hydrogel provided cross-protection against homologous and heterologous reinfection.
• Glycyrrhizic acid promoted bone tissue repair and modulated immune responses.

Conclusions:

• The developed hydrogel offers a promising platform for treating osteomyelitis by combining antimicrobial defense, immune memory, and tissue repair.
• This approach redefines osteomyelitis management and highlights the potential of immunomodulatory biomaterials for clinical translation.