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(1) formation of a specialized wound epidermis that functions to attract blastemal cells and maintain cell proliferation (Globus et al., 1980b, Thornton, 1957a, Thornton and Steen, 1962, Thornton and Thronton, 1965),

(2) dependence on innervation and exposure to nerve or Schwann cell secreted factors (Farkas et al., 2016, Kumar et al., 2007, Mescher et al., 1997, Mullen et al., 1996, Singer, 1952),

(3) formation of a pro-regenerative extracellular matrix (Calve et al., 2010, Gawriluk et al., 2016, Mailman and Dresden, 1979, Marrero et al., 2017, Onda et al., 1991, Satoh et al., 2012, Seifert et al., 2012, Tassava et al., 1996, Vinarsky et al., 2005),

(4) deployment of major developmental signaling pathways (rev. in Stoick-Cooper et al., 2007),

(5) physical interaction of cells from antonymic positions in three-dimensional space (Carlson, 1974, Cook and Seifert, 2016, Lheureux, 1975a, Lheureux, 1975b),

(6) recognition of uninjured versus new tissue and thus level-specific replacement of appropriate tissue to generate a complete organ and

(7) a dependence on macrophages to initiate regeneration (Godwin et al., 2013, Petrie et al., 2014, Simkin et al., 2017). Together, these features contribute to, and support, blastema formation, without which regeneration will not occur. Against the backdrop of these features epimorphic regeneration involves two major transformations in response to injury:

1) mature tissue into a blastema and 2) a blastema into a regenerated organ. Viewed in this light, the blastema is the link between healing and morphogenesis.