MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management
Gregory Lucien Bellot,
Xiaoke Dong,
Amitabha Lahiri,
Sandeep Jacob Sebastin,
Ines Batinic-Haberle,
Shazib Pervaiz,
Mark Edward Puhaindran
Affiliations
Gregory Lucien Bellot
Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Xiaoke Dong
Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore
Amitabha Lahiri
Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore
Sandeep Jacob Sebastin
Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore
Ines Batinic-Haberle
Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, USA
Shazib Pervaiz
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Medical Science Cluster Cancer Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University Cancer Institute, National University Health System, Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Australia; Corresponding author at: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Mark Edward Puhaindran
Department of Hand & Reconstructive Microsurgery, University Orthopedic, Hand & Reconstructive Microsurgery Cluster, National University Health System, Singapore; Corresponding author.
Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing. Keywords: Negative pressure wound therapy, Skin wound healing, Manganese superoxide dismutase, MnSOD mimetics, MnTE-2-PyP5+
