Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys

Abstract

ObjectiveBy observing the impact of Bevacizumab injection on the speed of wound healing and the expression of CD34 in cynomolgus monkeys, to verify its delayed wound healing mechanism, and to provide clinical reference for the dosage and frequency of Bevacizumab treatment for oncology surgery patients.MethodsSix male cynomolgus monkeys underwent full-thickness skin resection on the back to establish a wound healing evaluation model. Three cynomolgus monkeys were randomly selected as the saline group, and the other three cynomolgus monkeys were allocated to the Bevacizumab treatment group. The monkeys of Bevacizumab group were administrated with Bevacizumab injection (30 mg/kg, i.v.) on day 0, day 4, day 8, and day 11, respectively. The monkeys of saline group were injected with the same volume of saline as the group receiving Bevacizumab. The blood routine test was conducted, and the wound healing of each group of cynomolgus monkeys was observed 28 days after operation. The wound healing rate was analyzed by software Image J, and the severity of the wound was assessed by scoring method. Wound healing skin samples of 6 cynomolgus monkeys were obtained after 4 weeks, and the expression level of CD34 in the wound skin tissues was detected using immunohistochemistry.ResultsA skin excision wound model has already been established in cynomolgus monkeys. The number of white blood cells and neutrophils in the blood of cynomolgus monkeys increased significantly on the 3rd day after operation (P<0.05), and the number of white blood cells gradually returned to normal on the 7th day, while the number of red blood cells, hemoglobin and hematocrit did not change significantly, suggesting that the animals were in good nutritional status. The Bevacizumab injection group wound healing rate was significantly slower than that of the saline group on day 7, and day 28 (P<0.01, P<0.001). Microvessel density in the wound skin of Bevacizumab group appeared to be significantly lower than that of the saline group (P<0.01).ConclusionThe injection of Bevacizumab may delay the wound healing by inhibiting the angiogenesis in the new skin tissue of the cynomolgus monkey. In clinical practice, the timing of giving a tumor patient a bevacizumab injection after surgery should be based on the pros and cons, and the duration, dosage, and frequency of the intervention should be chosen in a rational way.

Keywords

• bevacizumab injection
• wound healing
• wound score
• cd34
• cynomolgus monkey