Nanomaterials in Wound Healing and Infection Control

Abstract

Wounds continue to be a serious medical concern due to their increasing incidence from injuries, surgery, burns and chronic diseases such as diabetes. Delays in the healing process are influenced by infectious microbes, especially when they are in the biofilm form, which leads to a persistent infection. Biofilms are well known for their increased antibiotic resistance. Therefore, the development of novel wound dressing drug formulations and materials with combined antibacterial, antibiofilm and wound healing properties are required. Nanomaterials (NM) have unique properties due to their size and very large surface area that leads to a wide range of applications. Several NMs have antimicrobial activity combined with wound regeneration features thus give them promising applicability to a variety of wound types. The idea of NM-based antibiotics has been around for a decade at least and there are many recent reviews of the use of nanomaterials as antimicrobials. However, far less attention has been given to exploring if these NMs actually improve wound healing outcomes. In this review, we present an overview of different types of nanomaterials explored specifically for wound healing properties combined with infection control.

Keywords: antimicrobial activity; antimicrobial nanomaterials; infection control; infectious microbes; nanoparticles; wound healing; wound management.

Figure 1

Summary of cellular targets (top) for metal and metal oxide nanoparticles and corresponding bacterial resistance mechanisms (bottom) in both Gram-positive (left) and Gram-negative (right) species. Before entry metal nanoparticles may produce reactive oxygen species (ROS), induce membrane fluidity and release metal ions [90]. Once inside the cell metal ions, nanoparticles or ROS may target the electron transport chain, ribosomes, DNA, proteins, lipids, carbohydrates and transport systems [90]. Bacteria respond by activating oxidative stress response proteins, DNA repair systems and metal efflux pumps [18,110,112]. Membrane modifications including an increase in flagellin, exopolysaccharides and changes to lipid composition can prevent metal entry by reducing electrostatic interactions and sequestering metal ions [18]. More resistant bacteria have also developed ways to modify metals into less toxic forms through reduction and/or bio-precipitation and nanoparticle aggregation [18,112,113].

Figure 2

Comparison of nanoparticle toxicity (left) and healing potential (right) at the wound interface. Nanoparticles have been shown to damage skin cells such as keratinocytes and fibroblasts by inducing ROS after entry through endocytosis causing mitochondrial damage, genotoxicity and lipid peroxidation [158,159]. Similar damage can occur to other cells in addition to protein damage, altered signaling and metabolism, reduced adhesion and migration and induced cell death [144,160,161]. Wound healing properties of metal nanoparticles are displayed on the right. For example, AgNPs have been associated with cytokine modulation leading to reduced inflammation, innate immune response and scarring, while also inducing keratinocyte differentiation and migration [162]. AuNPs have also displayed anti-inflammatory properties in addition to increasing epithelization and collagen deposition [124,163]. They can also modulate proteins involved in the healing process such as superoxide dismutase, interleukin-8, interleukin-12, tumor necrosis factor-alpha, vascular endothelial growth factor and angiopoietin [164]. Other nanoparticles including copper, zinc oxide and titanium dioxide have shown similar effects while also having antimicrobial properties and increasing angiogenesis [80,121].