Basic amino acid-mediated cationic amphiphilic surfaces for antimicrobial pH monitoring sensor with wound healing effects.

Background: The wound healing process is a complex cascade of physiological events, which are vulnerable to both our body status and external factors and whose impairment could lead to chronic wounds or wound healing impediments. Conventional wound healing materials are widely used in clinical management, however, they do not usually prevent wounds from being infected by bacteria or viruses. Therefore, simultaneous wound status monitoring and prevention of microbial infection are required to promote healing in clinical wound management.

Methods: Basic amino acid-modified surfaces were fabricated in a water-based process via a peptide coupling reaction. Specimens were analyzed and characterized by X-ray photoelectron spectroscopy, Kelvin probe force microscopy, atomic force microscopy, contact angle, and molecular electrostatic potential via Gaussian 09. Antimicrobial and biofilm inhibition tests were conducted on Escherichia coli and Staphylococcus epidermidis. Biocompatibility was determined through cytotoxicity tests on human epithelial keratinocytes and human dermal fibroblasts. Wound healing efficacy was confirmed by mouse wound healing and cell staining tests. Workability of the pH sensor on basic amino acid-modified surfaces was evaluated on normal human skin and Staphylococcus epidermidis suspension, and in vivo conditions.

Results: Basic amino acids (lysine and arginine) have pH-dependent zwitterionic functional groups. The basic amino acid-modified surfaces had antifouling and antimicrobial properties similar to those of cationic antimicrobial peptides because zwitterionic functional groups have intrinsic cationic amphiphilic characteristics. Compared with untreated polyimide and modified anionic acid (leucine), basic amino acid-modified polyimide surfaces displayed excellent bactericidal, antifouling (reduction ~ 99.6%) and biofilm inhibition performance. The basic amino acid-modified polyimide surfaces also exhibited wound healing efficacy and excellent biocompatibility, confirmed by cytotoxicity and ICR mouse wound healing tests. The basic amino acid-modified surface-based pH monitoring sensor was workable (sensitivity 20 mV pH^-1) under various pH and bacterial contamination conditions.

Conclusion: Here, we developed a biocompatible and pH-monitorable wound healing dressing with antimicrobial activity via basic amino acid-mediated surface modification, creating cationic amphiphilic surfaces. Basic amino acid-modified polyimide is promising for monitoring wounds, protecting them from microbial infection, and promoting their healing. Our findings are expected to contribute to wound management and could be expanded to various wearable healthcare devices for clinical, biomedical, and healthcare applications.