Smart Dressings Based on Nanostructured Fibers Containing Natural Origin Antimicrobial, Anti-Inflammatory, and Regenerative Compounds

Abstract

A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients' quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies). The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory properties together with nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about the beneficial or inert effects of those natural origin occurring materials, the scientific community leads towards the identification of the main active components involved and their mechanism of action during the corresponding healing, antimicrobial, or regenerative processes and in carrying out systematic and comparative controlled tests. Once those natural origin components have been identified and their efficacy validated through solid clinical trials, their combination within nanostructured dressings can open up new avenues in the fabrication of bioactive dressings with outstanding characteristics for wound care. The motivation of this work is to analyze the state of the art in the use of different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring materials as antimicrobial, anti-inflammatory and regenerative components with the aim of clarifying their potential clinical use in bioactive dressings. We conclude that, for those natural occurring materials, more clinical trials are needed to reach a sufficient level of evidence as therapeutic agents for wound healing management.

Keywords: chronic wounds; dressings; electrospinning; essential oils; honey; infection; inflammation; nanostructured materials; regeneration; tissue engineering.

Figure 1

Schematic representation of human adult skin. Five different layers form the stratified epidermis: stratum corneum (a), stratum lucidum (b), stratum granulosum (c), stratum spinosum (d) to the stratum basal (e) [1]. (Copyright Karger Publishers 2015).

Figure 2

Normal wound healing stages with the main events involved.

Figure 3

Wound healing stages: inflammation (a), proliferation (b) and tissue remodeling (c). (a) Inflammation is characterized by blood vessel injury, coagulation, and acute local inflammatory response with the formation of the protective clot against microbial infections; (b) The proliferation phase involves cell migration, granulation tissue formation, and angiogenesis; (c) Tissue remodeling implies the formation of a disorganized ECM as is depicted in the picture as well as a slightly elevated area together with the lack of normal skin appendages [22]. (Copyright Nature Publishing Group 2008).

Figure 3

Wound healing stages: inflammation (a), proliferation (b) and tissue remodeling (c). (a) Inflammation is characterized by blood vessel injury, coagulation, and acute local inflammatory response with the formation of the protective clot against microbial infections; (b) The proliferation phase involves cell migration, granulation tissue formation, and angiogenesis; (c) Tissue remodeling implies the formation of a disorganized ECM as is depicted in the picture as well as a slightly elevated area together with the lack of normal skin appendages [22]. (Copyright Nature Publishing Group 2008).

Figure 4

Scanning Electron Microscopy (SEM; a,b,d,e) and Transmission Electron Microscopy (TEM; c,f) micrographs of nanofibrous scaffolds, consisting of polylactic acid (PLLA)/polycaprolactone (PCL) (a,b) and chitosan (d,e) polymers, synthetized by electrospinning technique (unpublished results).

Figure 5

Electrospinning experimental set-up with its main components: syringe pumps, tip and collector. Coaxial injection capillaries can be used (image on the right) to fabricate nanofibrous core-shell structures.

Figure 6

Dressing model using an agar plate. (a) arrows indicate the cold pressed Valencia orange oil spots on gauze dressing pad; (b) complete setup of dressing model with gauze dressing pad wrapped with bandage. Untreated control plates of bacterial strains S. aureus: (c) COL; (d) Mu50; and (e). Inhibition of S. aureus: (f) COL; (g) Mu50; and (h) caused by the cold pressed Valencia orange oil [191]. (Copyright BioMed Central 2012).

Figure 7

(a) Photographs obtained from wounds covered with (A) gauze, (B) Comfeel^® Plus, and (C) electrospun PCL/PLA (50/50) nanofibrous mats containing thymol at different times: 1, 3, 7, 10, and 14 days. (b) Degree of closure (%) for wounds treated with gauze, Comfeel Plus, and electrospun PCL/PLA (50/50) nanofibrous mats containing thymol after days of post-treatment [205]. (Copyright Jonn Wiley & Sons 2013)

Figure 7

(a) Photographs obtained from wounds covered with (A) gauze, (B) Comfeel^® Plus, and (C) electrospun PCL/PLA (50/50) nanofibrous mats containing thymol at different times: 1, 3, 7, 10, and 14 days. (b) Degree of closure (%) for wounds treated with gauze, Comfeel Plus, and electrospun PCL/PLA (50/50) nanofibrous mats containing thymol after days of post-treatment [205]. (Copyright Jonn Wiley & Sons 2013)