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

Shengbing Yang,Hongbo Zhang,Tingting Tang,Xiuguo Han,Yuhang Jia

doi:10.3390/polym9120697

Abstract

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.

Highlights

The healing of wounds, especially extensive full-thickness wounds, is one of the most challenging clinical problems [1,2]
The nanofibrous membranes can provide an effective physical barrier to protect the open wound from further physical damage and contamination from exogenous micropathogens and serve as a template for the skin cells in the self-repairing process [14]
Various biocidal substances like silver, antibiotics, chitosan, iodine and poly-ammonium salts have been incorporated into nanofibrous membranes to produce an antibacterial effect [22,23,24,25]

Summary

Introduction

The healing of wounds, especially extensive full-thickness wounds, is one of the most challenging clinical problems [1,2]. A range of dressing types has been fabricated and used in accelerating wound healing and skin regeneration. Various processing techniques, such as lyophilization, 3D printing, solvent casting and electrospinning, can be used to produce membranes for wound dressing [6,7,8,9,10]. Electrospun nanofibrous membranes display high porosity with excellent pore interconnectivity and exhibit unique advantages for functional wound dressing materials [11,12,13]. The nanofibrous membranes can provide an effective physical barrier to protect the open wound from further physical damage and contamination from exogenous micropathogens and serve as a template for the skin cells in the self-repairing process [14]. There is an apparent need for more effective antimicrobial agents suitable for use in both preventative measures and the prevention of microbial colonization in open wounds; these agents must be further investigated

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