Uniting Drug and Delivery: Metal Oxide Hybrid Nanotherapeutics for Skin Wound Care

Abstract

Wound care and soft tissue repair have been a major human concern for millennia. Despite considerable advancements in standards of living and medical abilities, difficult-to-heal wounds remain a major burden for patients, clinicians and the healthcare system alike. Due to an aging population, the rise in chronic diseases such as vascular disease and diabetes, and the increased incidence of antibiotic resistance, the problem is set to worsen. The global wound care market is constantly evolving and expanding, and has yielded a plethora of potential solutions to treat poorly healing wounds. In ancient times, before such a market existed, metals and their ions were frequently used in wound care. In combination with plant extracts, they were used to accelerate the healing of burns, cuts and combat wounds. With the rise of organic chemistry and small molecule drugs and ointments, researchers lost their interest in inorganic materials. Only recently, the advent of nano-engineering has given us a toolbox to develop inorganic materials on a length-scale that is relevant to wound healing processes. The robustness of synthesis, as well as the stability and versatility of inorganic nanotherapeutics gives them potential advantages over small molecule drugs. Both bottom-up and top-down approaches have yielded functional inorganic nanomaterials, some of which unite the wound healing properties of two or more materials. Furthermore, these nanomaterials do not only serve as the active agent, but also as the delivery vehicle, and sometimes as a scaffold. This review article provides an overview of inorganic hybrid nanotherapeutics with promising properties for the wound care field. These therapeutics include combinations of different metals, metal oxides and metal ions. Their production, mechanism of action and applicability will be discussed in comparison to conventional wound healing products.

Nanomaterial-Based Therapy for Wound Healing

“…Copyright Elsevier, 2020) and corresponding timelines (lower) [11] (Reprinted with permission from Ref. [11]). [10] (Reprinted with permission from Ref.…”

“…Initially, hemostasis is the primary response to injury, stopping bleeding and abating hemorrhaging followed by vascular injury. Hemostasis involves three stages; vasoconstriction followed by primary hemostasis and then secondary hemostasis, which is attained through fast, synchronized, and mechanistically interrelated routes [11][12][13][14]. Table 1 represents the function of various biomolecules involved in wound healing.…”

“…The last stage of wound healing is maturation and remodeling. This phase starts about three weeks post wound development and can take one year or even more, based on the type of wound, resulting in the natural epithelium growth and scar tissue maturation [11]. This phase is simply the balance between synthesis, deposition, and degradation.…”

Vesicular Nanocarriers for Phytocompounds in Wound Care: Preparation and Characterization

“…It involves four successive and partially overlapping stages: hemostasis, the inflammatory phase, the proliferative phase, or granulation and maturation, also called remodeling. During these stages, numerous changes and interactions take place between the cells and the mediators at the wound site, leading to the healing of the tissue, with the restoration of the integrity and functions of the skin [ 5 , 14 , 15 ].…”

“…Thus, type III collagen, initially synthesized at high levels, is replaced by type I collagen, the dominant fibrillar collagen in the skin. Maturation also implies the reduction in the number of capillaries, increase in tensile strength, and decrease in cell density and metabolic activity in the granulation tissue [ 5 , 14 , 15 , 16 , 17 ]. A summarization of the wound-healing process is presented in Figure 1 .…”