Preparation and characterization of protein templated metal nano- formulations and their wound healing applications

Abstract

The skin is the largest human body organ that, by acting as a barrier, assists in preventing the entry of harmful microbes into the body. It can self-heal to a certain extent, which is impaired in case of extensive damage caused by chemical or physical shock. Wound healing activates multiple physiological and simultaneous phases, such as hemostasis, inflammation, proliferation, and remodeling. Different approaches have been used to treat chronic wounds, ranging from multiple dressings, stem cell-based therapies, and the use of growth factors. But still, certain limitations prevent their effective utilization, including delayed healing due to moisture, such as in alginatebased materials, delay due to poor aeration in hydrocolloidal dressings, poor mechanical strength in hydrogels, expensive production in therapies involving stem cells and growth factors and poor costeffectiveness. Wound treatment gain enormous interest of investigators, but there is a lack of efficient therapeutic intervention. The cost of healing ranges between $28.1 billion and $96.8 billion for acute and chronic wounds, and the maximum amount is used for surgical wounds, followed by diabetic ulcers. The alarming rise in chronic wounds, the increasing old-age population, and the hiking number of surgeries are some factors driving the growth of the wound care market. The number of patients affected by chronic wounds is approximately 5.7 million people in the United States alone, and an estimated cost of USD 25 billion is spent per year. Nanotechnology played a vital role in equipping us with promising approach for achieving target specific and efficient delivery through innovating protein-functionalized nanoparticles using growth factors, anti-diabetic wound healing agents (insulin), and extracellular proteins (keratin, heparin, and silk fibroin) as they are critical in enhancing cell proliferation, migration, ECM production, angiogenesis, and inflammation regulation. This led to the emergence of, protein-functionalized nanoparticles as a potential agents for accelerating healing in patients with delayed or impaired healing. Although insulin has huge potential as an anti-diabetic agent, but its role has rarely been explored in the field of wound-healing. This work aims to develop optimized protein-based nanoformulations for wound healing purposes as they can have sustained drug release, reduced administration frequency, an adequate concentration of medicine for an extended period, higher potency in wound recovery compared to the free proteins, high protein stability, easy transport through the body and less denaturation under environmental conditions, all work together to form advanced formulations critical for wound healing. Further, the high surface area to volume ratio, water solubility, stability, biocompatibility, target specificity, and biodegradability have given an upper hand to using nanoformulations over traditional therapeutics. Thus, I have synthesized protein-templated metal nanoformulations for their potential role as wound-healing agents under normal and diabetic conditions.