Abstract

Despite significant development in regenerative medicine, there is a deficit of effective therapies for wound healing and tissue regeneration. Research performed using animal wound models allows for a better understanding of this complex process, searching for compounds with pro-regenerative properties, and assessing their efficacy and safety. Unfortunately, the lack of adequate preclinical models proves to be an issue as no animal model can fully replicate human wounds. Nevertheless, new experimental therapies for enhancing wound healing and regeneration emerge, and animal models play an important role. Growth factors, cytokines, transcriptional activators in addition to small-molecule compounds such as epigenetic modulators seem to be of particular interest. In the presented work, I used an ear pinna punch wound in mice, a simple model of complex tissue injury, to examine the pro-regenerative effects for a selection of small-molecule compounds. One of the tested compounds, zebularine, a DNA methyltransferase inhibitor, administered intraperitoneally, significantly promoted wound closure in ear pinna. Furthermore, a combination treatment of zebularine and retinoic acid resulted in complete wound closure by day 21 after injury, whereas without treatment ear pinna holes in mice remain for life. To the best of my knowledge, this research is the first example demonstrating the potential of an epigenetic modulator to stimulate endogenous regenerative potential in animals, thus indicating a new pharmacological strategy for regenerative therapies.

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