Bioengineered M13 Bacteriophage-GelMA Construct Modulates Immune Responses in a Preclinical Model of Sepsis

Area of Science:

• Biomaterials Science
• Immunomodulation
• Tissue Engineering
• Sepsis Research

Background:

• Sepsis is a life-threatening condition characterized by immune dysregulation and multi-organ dysfunction.
• Current sepsis treatments focus on infection control and symptom management, lacking definitive cures.
• Artificial lymphoid tissues (ALTs) show promise for localized immunomodulation but face limitations in biological function and structural integrity.

Purpose of the Study:

• To develop a novel bioink combining gelatin methacryloyl (GelMA) with M13 bacteriophage for enhanced artificial lymphoid tissues (ALTs).
• To evaluate the efficacy of M13-containing GelMA scaffolds in an established mouse model of polymicrobial sepsis.

Main Methods:

• A novel bioink was formulated by integrating M13 bacteriophage into GelMA.
• Three-dimensional (3D) bioprinted GelMA scaffolds, with or without M13 bacteriophage, were implanted into the spleen of C57BL/6 mice 35 days prior to sepsis induction via cecal ligation and puncture (CLP).
• Immune, histological, and biochemical parameters were assessed post-sepsis induction.

Main Results:

• M13-containing scaffolds exhibited enhanced printability, mechanical stability, cellularity, and angiogenesis compared to GelMA-only scaffolds.
• Mice treated with M13-infused scaffolds showed significantly reduced pro-inflammatory cytokines (TNF-α, IL-6) and increased anti-inflammatory cytokines (IL-10, TGF-β).
• Reduced bacterial load, organ injury (liver, lungs, kidneys), and circulating liver enzymes were observed in the M13-treated group.

Conclusions:

• Integrating M13 bacteriophage into GelMA bioink creates multifunctional biomaterials that enhance ALT stability and provide anti-inflammatory immunomodulation.
• This dual structural-immunological approach represents a novel strategy for developing advanced biomaterials for immune regulation and tissue engineering.
• The developed M13-GelMA bioink shows significant therapeutic potential for mitigating sepsis-induced inflammation and organ damage.