Injectable self-healing hydrogel loaded with a self-assembling LL-37 derivative for treating infected skin wounds.

Area of Science:

• Biomaterials Science
• Infectious Disease Research
• Regenerative Medicine

Background:

• Effective management of infected skin wounds is challenging due to increasing antibiotic resistance.
• Antimicrobial peptides (AMPs) show promise but face limitations like poor stability and toxicity.
• LL-37, a human cathelicidin, serves as a basis for developing new therapeutic agents.

Purpose of the Study:

• To design and develop a novel, stable antimicrobial peptide (FR-20) derived from LL-37.
• To create an injectable, self-healing chitosan hydrogel (CS/FR-20) for enhanced drug delivery and wound healing.
• To evaluate the efficacy and safety of the CS/FR-20 hydrogel in treating infected skin wounds.

Main Methods:

• Rational design and synthesis of the FR-20 peptide with enhanced stability.
• Fabrication of an injectable, self-healing chitosan hydrogel using dynamic Schiff base cross-linking.
• In vitro assessment of hydrogel properties (mechanical integrity, injectability, cytocompatibility, hemocompatibility).
• In vitro antimicrobial testing against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA).
• In vivo evaluation in a murine full-thickness wound infection model.

Main Results:

• The CS/FR-20 hydrogel demonstrated excellent mechanical properties, injectability, and biocompatibility.
• CS/FR-20 exhibited potent bactericidal activity against both E. coli and MRSA.
• In vivo studies showed effective bacterial eradication, reduced inflammation, and accelerated tissue regeneration.
• No detectable systemic toxicity was observed in the animal model.

Conclusions:

• The developed CS/FR-20 hydrogel is a versatile and biocompatible platform for infected wound treatment.
• This approach offers a promising strategy to overcome antibiotic resistance.
• FR-20 loaded chitosan hydrogel effectively promotes wound healing and bacterial clearance.