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A novel nitric oxide delivery system for diabetic wounds
Mihail Climov, M.D.1,7 , Yukun Liu, M.D.1,2, Songxue Guo, M.D., M.S.1,3, Shuyi Wei, M.D.1,4, Huan Wang, M.D.1,4, Yong Liu, M.D.1,5, Andrea V. Moscoso, B.A.1, Zina Ribkovskaia, Ph.D.6, Tsvetelina Lazarova, Ph.D.6, Steven Riesinger, Ph.D.6, Dennis P. Orgill, M.D., Ph.D.1,
1 Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2 Department of Plastic Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
3 Department of Plastic Surgery, Second Affiliated Hospital, Zhejiang University, College of Medicine, Hangzhou 310009, Zhejiang, China.
4 Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shi-Jing-Shan District, Beijing, China.
5 Department of Burn and Plastic Surgery, West China Hospital, Sichuan University,
Chengdu, China.
6 MedChem Partners LLC. Lexington, MA, USA
7 Division of Plastic Surgery, Ruby Memorial Hospital, West Virginia University, Morgantown, WV, USA
West Virginia University, Ruby Memorial Hospital
2019-02-15
Presenter: Mihail Climov
Affidavit:
"agree with submission"
Director Name: Aaron Mason
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Diabetic foot ulcers represent a major healthcare problem. Externally delivered Nitric Oxide (NO) is a potent modulator of wound healing capable of accelerating diabetic wound healing. Currently, the most common delivery method to the wound is in gaseous form. Such practice is dangerous and not cost-efficient. The current work explores a novel paradigm of NO delivery in form of a stable, nontoxic gel that produces NO when in contact with wound exudate. This hypothesis was tested in vivo on a murine diabetic wound model. A total of 4 experimental groups (n=12), two concentrations: 100 μM, 1000 μM, and two controls: a gel-control, and the untreated groups were tested. Wound contraction was assessed by planimetry for a duration of one week. Granulation tissue, CD31, and α-SMA expressions were measured at the end of the tested period.
Although no statistically significant difference in wound healing kinetics between the experimental groups was found, the histological evaluation showed a significant increase in granulation tissue thickness in both Gel 100 and Gel-control (p < 0.05). Gel 100 exhibited a significant impact on the expression of angiogenesis markers CD31 and α-SMA (p < 0.05). Gel 1000 appears to have an inhibitory effect on angiogenesis as compared to Gel 100.
This preliminary study showed that the proposed NO gel has a dose-dependent effect on CD31 and α-SMA. While this study shows the potential of this delivery method, further studies to optimize as well as testing remaining formulations are streamlined
