Hydroxypropyltrimethyl Ammonium Chloride Chitosan Functionalized-PLGA Electrospun Fibrous Membranes as Antibacterial Wound Dressing: In Vitro and In Vivo Evaluation

摘要

A novel poly(lactic-co-glycolic acid) (PLGA)-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) composite nanofiber wound dressing was prepared through electrospinning and the entrapment-graft technique as an antibacterial dressing for cutaneous wound healing. HACC with 30% degrees of substitution (DS) was immobilized onto the surface of PLGA membranes via the reaction between carboxyl groups in PLGA after alkali treatment and the reactive groups (–NH2) in HACC molecules. The naked PLGA and chitosan graft PLGA (PLGA-CS) membranes served as controls. The surface immobilization was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA) and energy dispersive X-ray spectrometry (EDX). The morphology studies showed that the membranes remain uniform after the immobilization process. The effects of the surface modification by HACC and CS on the biological properties of the membranes were also investigated. Compared with PLGA and PLGA-CS, PLGA-HACC exhibited more effective antibacterial activity towards both Gram-positive (S. aureus) and Gram-negative (P. aeruginosa) bacteria. The newly developed fibrous membranes were evaluated in vitro for their cytotoxicity using human dermal fibroblasts (HDFs) and human keratinocytes (HaCaTs) and in vivo using a wound healing mice model. It was revealed that PLGA-HACC fibrous membranes exhibited favorable cytocompatibility and significantly stimulated adhesion, spreading and proliferation of HDFs and HaCaTs. PLGA-HACC exhibited excellent wound healing efficacy, which was confirmed using a full thickness excision wound model in S. aureus-infected mice. The experimental results in this work suggest that PLGA-HACC is a strong candidate for use as a therapeutic biomaterial in the treatment of infected wounds.