Moist exposed burn ointment promotes cutaneous excisional wound healing in rats involving VEGF and bFGF

Abstract

Abstract. Cutaneous delayed wounds are a challenging clinical problem, and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) exhibit key roles in wound healing. Moist exposed burn ointment (MEBO), a Chinese burn ointment with a USA patented formulation, has been reported to promote chronic ischemic and neurogenic ulcer healing in patients; however, the underlying mechanisms remain unclear. In the present study, MEBO significantly promoted the formation of granulation tissue in cutaneous excisional wounds, shortened the time of wound healing, and increased neovascularization and the number of fibroblasts. Furthermore, as well as enhancing the protein expression, MEBO application also increased the gene expression of VEGF and bFGF. The results indicate that MEBO promotes cutaneous excisional wound healing by at least partially enhancing VEGF and bFGF production, implicating the potential uses of MEBO for delayed cutaneous wound healing. IntroductionCutaneous wounds, known as ulcers, are an extremely common clinical problem and often arise following acute or chronic mechanical causes, physical or chemical burns, frostbite, infections, and disorders, including rheumatism, diabetes, peripheral vascular disease, lipodermatosclerosis and malignant tumors (1,2). Furthermore, cutaneous wound healing may be significantly delayed due to the aforementioned factors. At present, delayed cutaneous wounds are one of major burdens for health care, and lead to a reduced quality of life in patients who suffer from this type of wound (3,4).Wound healing is a complicated biological process involving a series of dynamic events, including hemostasia, inflammation, cell proliferation and differentiation, neovascularization, granulation tissue formation, collagen synthesis, epithelialization, and wound contraction. Increasing evidence has established the hypothesis that growth factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are key regulators of normal and abnormal angiogenesis, and tissue repair in animals and humans (5-8). VEGF promotes angiogenesis/vasculogenesis and vascular permeability, and enhances endothelial cell proliferation and migration as well as the adhesion of leukocytes (5,9). Further research revealed that VEGF stimulates hydrogen sulfide synthesis and release from endothelial cells, thus leading to subsequent endothelial cell growth, migration and permeability, microvessel formation, and wound healing (10). In addition, VEGF promotes epithelialization and collagen deposition in the wound (11). FGF-2, known as bFGF, is a member of a large FGF family and induces angiogenesis, endothelial cell and fibroblast proliferation, and wound healing (12)(13)(14). Recent data indicated that bFGF-mediated angiogenesis refers to endothelial cell proliferation, migration and tube formation by activating c-Jun N-terminal kinase/stress-activated protein kinase signaling (15). Notably, the expression of VEGF and bFGF was increased following skin in...

Nerve growth factor and substance P may be involved in moist exposed burn ointment‑mediated chronic refractory wound healing

“…The results of this study showed that intervention with either MEBO or rb-bFGF increased wound-healing rates and reduced TNF-α and IL-6 overexpression in wound homogenate tissue, especially on the 7th day during treatment, and MEBO showed a more obvious effect. The improvement in wound healing was consistent with similar previous studies conducted with MEBO (5–9). Because MEBO and rb-bFGF do not contain anti-inflammatory drugs, we speculated that MEBO indirectly reduces the expression of some inflammatory factors, during wound-healing and improves the wound's microenvironment, thereby creating a positive physiological environment for wound cells to speed up the wound healing process.…”

“…After many years of improvement and development, MEBO has become a routine technical method that is widely used in many clinics. MEBO is mainly used to treat burns and a variety of body surface wounds with good results (5,6), and is a currently recognized technique in the academic community (7–9). However, the molecular mechanisms of MEBO in the process of burn treatment have not been studied.…”

The repairing of full-thickness skin deficiency and its biological mechanism using decellularized human amniotic membrane as the wound dressing

“…VEGF, acting as a symbol factor of blood vessels, could promote angiogenesis and enhance endothelial cell proliferation and migration [26,27]. It also had influences on wound closure and repairing, including the formation of granulation tissues.…”

Moist exposed burn ointment for treating pressure ulcers

“…[22] In addition, MEBO can increase neovascularization in granulation tissue, and enhance vascular endothelial cell proliferation. [34] It can also increase fibroblast cells in the granulation tissue and help them migrate from the surrounding connective tissue into the wound site. [35] …”