Multifunctional Cationic Hyperbranched Polyaminoglycosides that Target Multiple Mediators for Severe Abdominal Trauma...

Area of Science:

• Biomaterials Science
• Immunology
• Trauma Pathophysiology

Background:

• Trauma triggers severe complications like inflammation, infection, and DIC due to cell-free nucleic acids (cfNAs) acting as damage-associated molecular patterns (DAMPs).
• Biomaterial-based cfNA scavenging offers a potential therapeutic strategy to mitigate post-trauma systemic inflammation and coagulation abnormalities.

Purpose of the Study:

• To investigate the efficacy of cationic hyperbranched polyaminoglycosides (HPT) and disulfide-included HPT (ss-HPT) in scavenging cfNAs.
• To evaluate their potential in mitigating post-trauma inflammation and hypercoagulation.

Main Methods:

• Synthesis of HPT and ss-HPT polymers derived from tobramycin.
• In vitro assessment of cfNA scavenging, DAMP-induced TLR activation, inflammatory cytokine secretion, and hypercoagulation.
• In vivo evaluation in a cecal ligation puncture (CLP) mouse abdominal trauma model, including organ accumulation, retention, and biodegradation studies.

Main Results:

• Both HPT and ss-HPT effectively scavenged cfNAs, suppressing TLR activation, cytokine release, and hypercoagulation.
• Polymers demonstrated antibacterial activity due to tobramycin.
• In the CLP model, HPT and ss-HPT modulated inflammation and improved therapeutic outcomes.
• ss-HPT showed enhanced accumulation in injured organs and faster biodegradation in healthy mice compared to HPT.

Conclusions:

• Functionalized ss-HPT, a bioreducible polyaminoglycoside, effectively scavenges cfNAs and exhibits therapeutic potential.
• ss-HPT holds promise for enhancing trauma patient outcomes by reducing inflammation and coagulation complications.