Goutham V Ganesh1,2, Kunka Mohanram Ramkumar3. 1. Life Science Division, SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, Tamilnadu, 603 203, India. 2. Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603 203, India. 3. Life Science Division, SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, Tamilnadu, 603 203, India. ramkumak@srmist.edu.in.
Abstract
PURPOSE: The failure in timely healing of wounds is a central feature in chronic wounds that leads to physiological, psychological and economic burdens. Macrophages have been demonstrated to have various functions in wounds including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells and tissue restoration following injury. Accumulated evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing wounds. While the overall signaling cascades have been well understood, their complex interplay and a detailed characterization of events that are disrupted in chronic wounds have still not emerged satisfactorily. METHODS: The existing literature was reviewed to summarize the regulation of macrophage polarization in wound closure and dysregulation in non-healing wounds. Further, the review also underscored the role of Nrf2 in promoting macrophage-mediated regulation in wound responses and in particular, macrophage involvement in iron homeostasis that is impaired in chronic wounds such as in diabetes. RESULTS: The mechanisms involved in the reprogramming of macrophage subtypes in chronic wounds are still emerging. Furthermore, treating non-healing wounds has increasingly been shifting focus from generic treatments to the development of targeted therapies. Increasing evidence suggests the need for modeling wound tissue in vitro which may very well serve a critical aspect to characterize the relevant factors that sustain chronic wounds in vivo such as the constant iron overload at the wound site from recurrent infection and bleeding. CONCLUSION: The development of targeted therapies and also developing a reliable means to monitor assisted healing of chronic wounds are two major goals to be pursued. In addition, identifying molecular targets that can regulate macrophages to aid tissue restoration in chronic wounds would serve the crucial step in realizing both aforementioned goals.
PURPOSE: The failure in timely healing of wounds is a central feature in chronic wounds that leads to physiological, psychological and economic burdens. Macrophages have been demonstrated to have various functions in wounds including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells and tissue restoration following injury. Accumulated evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing wounds. While the overall signaling cascades have been well understood, their complex interplay and a detailed characterization of events that are disrupted in chronic wounds have still not emerged satisfactorily. METHODS: The existing literature was reviewed to summarize the regulation of macrophage polarization in wound closure and dysregulation in non-healing wounds. Further, the review also underscored the role of Nrf2 in promoting macrophage-mediated regulation in wound responses and in particular, macrophage involvement in iron homeostasis that is impaired in chronic wounds such as in diabetes. RESULTS: The mechanisms involved in the reprogramming of macrophage subtypes in chronic wounds are still emerging. Furthermore, treating non-healing wounds has increasingly been shifting focus from generic treatments to the development of targeted therapies. Increasing evidence suggests the need for modeling wound tissue in vitro which may very well serve a critical aspect to characterize the relevant factors that sustain chronic wounds in vivo such as the constant iron overload at the wound site from recurrent infection and bleeding. CONCLUSION: The development of targeted therapies and also developing a reliable means to monitor assisted healing of chronic wounds are two major goals to be pursued. In addition, identifying molecular targets that can regulate macrophages to aid tissue restoration in chronic wounds would serve the crucial step in realizing both aforementioned goals.
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