Antimicrobial Peptide-Functionalized Mesoporous Hydrogels.

Saba Atefyekta,Anand K Rajasekharan,Sara Svensson,Martin Andersson,Edvin Blomstrand,Thomas J Webster,Margarita Trobos,Peter Thomsen,Jaan Hong

doi:10.1021/acsbiomaterials.1c00029

Abstract

Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10–100× less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.

Highlights

Human skin is an effective barrier protecting underlying tissues from microbial penetration, but it is the tissue most exposed to damage and injury.[1]
We developed an antimicrobial hydrogel by covalent immobilization of a cationic antimicrobial peptides (AMPs), RRPRPRPRPWWWW-NH2 (RRP9W4N), onto ordered amphiphilic mesoporous hydrogels made of cross-linked Pluronic F127 triblock copolymer and water
A hydrogel consisting of a cross-linked diacrylatemodified triblock copolymer (F127) and water was used as a substrate for AMPs functionalization

Summary

Introduction

Human skin is an effective barrier protecting underlying tissues from microbial penetration, but it is the tissue most exposed to damage and injury.[1]. Microbial analysis is often both a challenging and time-consuming procedure.[5] In some cases, bacteria present in the wound have the ability to form and exist within a biofilm Such biofilms have a complex structure and are usually resistant to host immune responses and antibiotic treatments.[6,7] systemic antibiotic treatment often does not provide the right antibiotic concentration to the infected site and has been shown ineffective in chronic granulating wounds.[3,8] Most importantly, antibiotic resistance is an increasing concern in wound infections, and the Center for Disease Control in the United States is predicting more deaths from antimicrobial infections than from all cancers combined by 2050. Wounds colonized with multiresistant bacteria cause further morbidity to the patient and certainly complicate wound management.[9−11]

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Conclusion