Nanocoatings for Chronic Wound Repair-Modulation of Microbial Colonization and Biofilm Formation

Abstract

Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches.

Keywords: antimicrobial nanoparticles; biofilm formation; chronic wound; nanocoatings; tolerance.

Figure 1

Acute wound healing consists of the coagulation and inflammatory phase, the proliferation and tissue formation phase, and the maturation and remodeling phase. Abbreviations: PDGF—platelet-derived growth factor; TGF-α1, TGF-α2—transforming growth factors alpha 1 and alpha 2; VEGF—vascular endothelial growth factor; FGF-β—fibroblast growth factor beta; GM-CSF—granulocyte-macrophage colony-stimulating factor; TLR—Toll-like receptor; PAMP—pathogen-associated molecular pattern.

Figure 2

Nanoparticles embedded within bioactive wound dressings could enhance the delivery to the target of beneficial molecules with antimicrobial, immunomodulatory, and regenerative effects. In regard to the antimicrobial action, an ideal therapeutic agent should destroy pathogenic bacteria but also modulate microbial colonization, attachment, and biofilm development; modulate and promote beneficial bacterial phenotypes; modulate inter-bacterial and host-microbiome interactions. The agent should achieve immunomodulatory action by supporting the host’s defense mechanisms, as well as regenerative effects, by the enhancement of wound healing and tissue regeneration.

Figure 3

Clinical application of silver-containing impregnated dressing for wound healing. (A) Initial stage in which the wound is highly infected, a stage at which Dr. Laurentiu Leica took into consideration the possibility of skin grafting; (B) The use of a silver-containing impregnated polyamide dressing; (C,D) The beneficial effect of the dressing at 2 weeks and at one month, respectively, of follow-up. It was observed that the dressing not only exhibited antimicrobial effects but also promoted wound healing.