Comparative Evaluation of Antimicrobial Peptide and Chlorin e6 Immobilization Strategies on GelMA Hydrogels for Enhanced Antibiofilm Activity via Photodynamic Therapy.

Abstract

Chronic wounds pose a significant health challenge that affects millions of people worldwide. Traditional treatments, such as antibiotics, have limitations, including the development of antibiotic resistance. Antimicrobial peptides (AMPs) are gaining attention due to their broad-spectrum antimicrobial activity, including against multidrug-resistant strains. TetraF2W-RR, a specific AMP, has shown promise in combating various bacteria, particularly when incorporated into wound dressings. Another emerging antimicrobial approach is photodynamic therapy (PDT), which utilizes photosensitizers (PS), such as chlorin e6 (Ce6), activated by light to destroy bacteria without inducing resistance. Ce6 offers advantages such as rapid photosensitization, selective accumulation in target areas, and minimal side effects, making it a favorable candidate for PDT in wound treatment. Furthermore, combining AMPs with PDT offers a combined approach for enhanced antibacterial activity. Although hydrogel dressings, particularly GelMA, provide an ideal environment for wound healing, GelMA lacks intrinsic antimicrobial properties and can promote bacterial growth. Therefore, combining GelMA with antimicrobial strategies is crucial. Herein, to investigate the influence of different strategies on antimicrobial efficiency, two distinct approaches were developed for the functionalization of GelMA with AMP and Ce6. This is the first comparative study of different AMP and PS conjugation strategies for enhancing PDT on hydrogels. In the first approach, the Ce6@AMP conjugate was immobilized onto GelMA (GelMA/Ce6@AMP). In the second approach, AMP and Ce6 were separately conjugated to GelMA via EDC/NHS chemistry (GelMA/AMP/Ce6). GelMA/Ce6@AMP hydrogels significantly lost their antibacterial activity, whereas GelMA/AMP/Ce6 hydrogels maintained strong antimicrobial and anti-biofilm effects, which clearly demonstrates the impact of conjugation strategy on antibacterial performance.