Application of microbubbles in wound healing

Introduction: Overcoming the factors that help reduce wound healing process is a key holistic approach to wound care and presents early challenges in the treatment of chronic wounds. When wounds fail to heal after four weeks of standard care, consideration should be given to the underlying pathology of advanced therapeutic agents. However, the choice of appropriate treatment is often not evidence-based. Basic concepts should usually be followed. Systematic evaluation of patients and their wounds also facilitates appropriate care.Wounds are associated with pain and scarring. Multiple techniques have been developed in the past to overcome these limitations but have been unable to achieve clinical relevance. The repair of such wounds involves complex biological and dynamic processes such as Hemostasis, inflammation, proliferation and Maturation. Several factors contribute to the challenges of wound management, including the location, size and depth of the wound, and the presence of severe bleeding. Various factors such as oxygen, infection, age and sex hormones, stress, diabetes, obesity, medications, alcohol, smoking are effective in wound healing and repair, which are classified into local and systemic factors.Oxygen as one of the main factors in wound healing has always attracted researchers attention. Some scientists have been using oxygen to reduce the wound healing period and to use less therapeutic and pharmaceutical materials. Oxygen is important for cellular metabolism, especially energy production using ATP and is critical for almost all wound healing processes. Presence of oxygen prevents infection, induces angiogenesis, increases keratinocyte differentiation, increases fibroblast production and collagen synthesis, wound contraction, and ultimately tissue formationIn light of the above, the researchers in the field of wound healing, in part of their research, have been looking for inadequate oxygen compensation at the wound site to accelerate wound healing. One of these methods has been the use of microbubbles or nanobubbles, which are also used in non-medical sciences. The following is an overview of the conventional methods of wound healing, followed by a review of the use of micro-bubbles in wound healing.Method: This paper is a review study which aims to provide readers enough information about employing microbubbles for wound healing. To do this, we have done our research by looking for new and late studies. First, we presented a short expression of wounds, the process of wound healing, main factors that accelerate wound healing and some common treatments. Then, explained the importance of oxygen in wound healing process and the effects that it may has on wound. In follow, we introduced microbubbles and provided enough information about its application in wound healing process and the way they are employed. Also, various usages of microbubbles as carrier was discussed. Finally, as conclusion, the main keynotes were classified and a short description about the negative aspects of the microbubbles revealed.Findings: Wound healing involves the stages of blood clotting, angiogenesis, and skin repair. This process occurs well when growth factors and cytokines (a protein molecule responsible for transmitting messages between cells) are supplied. Therapeutic agents including growth factors, cytokines, antibacterial agents, proteins and bioactive agents accelerate the wound healing process.Recent advances in drug release systems (DDSs) to release growth factors (GFs) have provided more therapeutic opportunities. These advances appear especially in the area of wound healing and skin healing.The small size of the particles increases the penetration of the drug into the wound bed. Nanoparticles such as peptides or nucleic acids are used to transport biological substances intracellularly.Using micro-modulators, macromolecules can be encapsulated to protect against environmental factors and to release drug better on the wound bed. The nanoparticle drug delivery system releases the drug in a controlled manner at a given concentration. This system increases the half-life of the drug, optimizes the absorption and desorption profile of the drug and also reduces the fluctuation of the drug concentration.Hydrogels enhance the period of treatment because they can maintain moisture on the surface of wound and make a proper environment for regenerate. To release active component is based on the porous size of network, which is controlled by cross-linking and swelling. However, drug release from hydrogel is faster than other methods (Micro and Nano micelles, fat nanoparticle, nanofibers, and scaffold).According to previous studies, oxygen is a crucial factor in the wound healing, and generally tissue oxygen and nutrients are needed to growth tissue when wound is made and tissue need regeneration. Evidence shows that the improvement of oxygen transfer may be useful in the around of wound infection. Sufficient oxygen can increase the formation of granulated grains and synthesis of collagen. Meanwhile, in aerobic metabolism of glucose, cells use oxygen as new electron receiver for production of ATP. In 2008, researchers showed that microbubbles can be used as a medical device for oxygen transfer to tissue. In one study, a new platform for transdermal drug delivery platform was developed using microbubbles to accelerate wound healing. In this study, no mention was made of the importance of oxygen, but the presence of microbubbles as drug carriers has been identified as one of the factors influencing rapid wound healing. Passive targeting as a method of drug delivery is known as the most appropriate method for delivering microbubbles at a specified site. One of the benefits of microbubbles in this regard is that the accumulation of microbubbles in the injured site can help in the purposeful identification of infection and malignancies. Microbubbles reside in the infected tissue and facilitate the imaging of different infected sites. Microbubbles can penetrate deep into the tissues of the body.Conclusion: Wounds healing or helping to heal tissue or destroying annoying cells such as cancer cells have been the focus of scientists and researchers with the aid of microbubbles. Not only oxygen but also other therapuitic agents, drugs, genes, and chemotherapy agents can be transferred and delivered by microbubbles. Microbubbles proved to be a good strategy to accelerate wound healing. In general, microbubbles have been able to attract researchers attention in the wound healing process. Despite much research being done in this area, there are still challenges and medical problems that need further investigation. Microbubbles, although useful in many ways, can be harmful if not used properly. In the publications, there have been reports of damage to tissue or vessels and capillaries as a result of the use of microbubbles. In some treatments such as cardiac surgery, the use of microbubble flow can damage the vessels and capillaries of the surgical site [55]. However, microbubbles have been shown to be capable of repairing injuries and helping drug delivery and can be used in future research.

Keywords:

Microbubbles , Oxygen , wound Healing , hydrogel