T. Tsuge1, M. Aoki1, K. Kubomura1, S. Akaishi1, K. Takabe2, R. Ogawa1 2Roswell Park Cancer Institute,Breast Surgery,Buffalo, NY, USA 1Nippon Medical School,Plastic, Reconstructive And Aesthetic Surgery,Tokyo, , Japan
Introduction:
Deep dermal burn (DDB) is an injury with epidermal, superficial and deep dermal damages. Its healing often requires longer than a month despite appropriate treatment, and sometimes results in hypertrophic scar. During such a long period of healing process, DDBs can easily proceed to deeper burn wound due to infection through necrotic tissues. Therefore, a novel treatment that can activate macrophage functions to promoting epithelialization is anticipated as a breakthrough in burn treatment. Sphingosine-1-phosphate (S1P) is a lipid mediator that is involved in immune cell migration, angiogenesis, and cell proliferation. In particular, S1P plays an important role in inflammatory cell recruitment into local tissues. Further, S1P receptor 1 signaling is essential for angiogenesis. We focused on S1P as a new approach for wound treatment. We investigated the therapeutic effects in rat DDB model.
Methods:
Four of 10 mm-diameter hair-removed skin areas were contacted with 78 ºC water for 10 seconds to create DDBs in F344 rats (male, 8-12 week). Topical application with control or S1P ointment was performed every other day until day 14 after injury. We performed burn area analysis, and analyzed macrophage recruitment and microvessels by immunohistochemistry. 3D photo acoustic imaging system was used to estimate angiogenesis in burn area. Microvascular integrated densities were calculated using ImageJ.
Results:
Topical application of S1P significantly promoted deep burn wound healing of DDBs comparing with control. Average of burn wound areas treated with vehicle at day 12 was 32.2 % of day 0, whereas average of those treated with S1P was 17.1 % (p=0.039). Surprisingly, we found that autolysis of necrotic tissues was promoted in DDBs treated with S1P. This results suggests that macrophage recruitment is increased by S1P treatment. Further, by analysis with 3D photo acoustic imaging, we found that microvascular integrated density in burn areas treated with S1P was significantly higher than that treated with control at day 14 after injury. This result demonstrates that topical S1P promote angiogenesis.
Conclusion:
Our results show that topical application of S1P promote deep dermal burn wound healing by recruitment of macrophages, promoted autolysis of necrotic tissues, and enhanced angiogenesis. It is suggested that increased macrophages by S1P treatment may remove necrotic tissues, prevent infection, and promote angiogenesis. Thus, S1P may have a role as novel approach for wounds with necrotic tissues such as DDBs.