Iron Nanoparticles Open Up New Directions for Promoting Healing in Chronic Wounds in the Context of Bacterial Infection

Abstract

Metal nanoparticles play an outstanding role in the field of wound healing due to their excellent properties, and the significance of iron, one of the most widely used metals globally, cannot be overlooked. The purpose of this review is to determine the importance of iron nanoparticles in wound-healing dressings. Prolonged, poorly healing wounds may induce infections; wound infections are a major cause of chronic wound formation. The primary components of iron nanoparticles are iron oxide nanoparticles, which promote wound healing by being antibacterial, releasing metal ions, and overcoming bacterial resistance. The diameter of iron oxide nanoparticles typically ranges between 1 and 100 nm. Magnetic nanoparticles with a diameter of less than 30 nm are superparamagnetic and are referred to as superparamagnetic iron oxide nanoparticles. This subset of iron oxide nanoparticles can use an external magnetic field for novel functions such as magnetization and functionalization. Iron nanoparticles can serve clinical purposes not only to enhance wound healing through the aforementioned means but also to ameliorate anemia and glucose irregularities, capitalizing on iron's properties. Iron nanoparticles positively impact the healing process of chronic wounds, potentially extending beyond wound management.

Keywords: antibacterial ability; chronic wounds; iron nanoparticles; trauma dressings; wound healing.

Figure 1

Antiinfection strategies that inhibit the expression of virulence factors and prevent biofilm growth can be categorized as anti-quorum sensing, antitoxin, and anti-biofilm (left). Novel antibiotic alternatives aim to mitigate bacterial resistance by eradicating pathogens through nonspecific mechanisms involving cell membrane damage, oxidative stress, and interactions with genetic material and proteins (right). Source: Adapted with permission from earlier studies [20], Springer Nature.

Figure 2

Antibiotics are still used as the primary defense against bacterial infections. However, antibiotic misuse has led to the emergence of drug-resistant bacteria, potentially spiraling localized infections out of control within chronic wounds. Metallic nanoparticles, such as iron oxide nanoparticles, offer a countermeasure to antibiotic overuse, restraining bacterial infections and fostering wound healing.

Figure 3

Timeline of new antibiotics entering the clinic. Antibiotics are colored according to their source: green = actinomycetes, blue = other bacteria, purple = fungi, and orange = synthetic. Essential dates pertaining to antibiotic discovery and antimicrobial resistance are provided at the timeline’s base. * Indicates that synthesis was inspired by a natural product. Source: Adapted with permission from earlier studies [38], Elsevier.

Figure 5

(A) Inflammation. Hemostasis and inflammation can occur immediately after an injury. Blood extravasation leads to the formation of blood clots. Many signaling factors are released, causing inflammatory cells like neutrophils and monocytes to be re-attracted to the wound. The monocytes then differentiate into mature macrophages at the wound site. Both neutrophils and macrophages are phagocytic cells that act to cleanse the wound while releasing other factors that stimulate fibroblasts to converge at the wound site. (B) Proliferation and remodeling. During proliferation, fibroblasts secrete the extracellular matrix and form granulation tissue. Angiogenesis unfolds concurrently with the migration of endothelial cells to the wound’s vicinity. As an integral facet of the remodeling phase, matrix metalloproteinases concomitantly degrade the collagen secreted by fibroblasts. (C) Maturation ensues, wherein collagen synthesis and degradation achieve equilibrium. Disorderly collagen fibers undergo crosslinking and alignment along tension lines, consequently amplifying the wound’s tensile resilience. (D) Chronological progression of diverse processes in wound healing. Source: Adapted with permission from earlier studies [63], Advances in Wound Care.

Figure 6

Activation of HIF-1. Under hypoxia, HIF-1α stabilizes and binds to the HIF-1β subunit, forming the active transcription factor HIF-1. HIF-1 translocates to the nucleus, where it binds to hypoxia regulatory elements within the promoter region of HIF-1-inducible genes, along with coactivators p300 and CBP, to promote the expression of HIF-1 target genes, such as VEGF and SDF-1. Source: Adapted with permission from earlier studies [63], Advances in Wound Care.

Figure 8

Comprehensive mechanism of IONPs against bacterial cells. Source: Adapted with permission from earlier studies [83], Springer Nature.

Figure 4

When there is a lack of iron in the tissues, it leads to iron deficiency anemia, resulting in a shortage of oxygen and nutrients in the surrounding tissues. Conversely, an iron overload in the skin and tissues leads to excessive iron deposition, characterized by the presence of the hallmark substance, ferric hemosiderin. Whether the iron levels are deficient or excessive, abnormal iron levels can lead to compromised wound healing. By conducting research within the clinical setting, we have the opportunity to shift our focus from the hospital ward to the controlled environment of the research laboratory bench. This transition allows for a comprehensive investigation into the intricate correlation between iron levels and the process of wound healing.

Figure 7

On the one hand, IONPs can be administered to the wound through dressings, facilitating the gradual release of iron ions to rectify irregular local iron concentrations within the wound. Conversely, it modulates the blood glucose levels in diabetic patients by attenuating the activity of alpha-amylase.

Figure 9

Iron NPs, when integrated with antibiotics within wound dressings, hinder bacterial infection occurrence while curtailing antibiotic volume. Notably, SPIONs can more effectively and precisely infiltrate cell membranes and walls under the influence of external magnetic fields (The arrow indicates the direction of SPION movement), effectively transporting antibiotics for enhanced sterilization.