Vasoactive intestinal peptide supports induced migration of human keratinocytes and their colonization of an artificial polyurethane matrix

Abstract

We investigated the effect of the neuropeptides vasoactive intestinal peptide (VIP), ( d-Phe 2)-VIP, (Lys-Pro-Arg-Tyr)-VIP and the VIP fragment (1–12) on induced migration and colonization in vitro. In confluent keratinocyte cultures “wounded” with a razor blade, the VIP-treated samples disclosed a more rapid migration from the wound margins into the wound bed, starting within the first 4 h. Almost 80% of the wounded area was covered within 24 h. In contrast, VIP-derivatives were not significantly different from controls, covering 10 to 18% of the wounded area ( p<0.02). Colonization has been assessed with an artificial non-toxic polyurethane matrix. In controls, we were able to observe migration of keratinocytes on the matrix within the first 24 h. The cells, however, were not able to migrate further and to survive. After 48 h, VIP-treated cultures showed a complete colonization of the matrix by keratinocytes vs. less than 10% of the total area in controls ( p<0.001). The induction of migration and of colonization was VIP-dose-dependent. The data indicate that induced migration is stimulated by VIP, when the N-terminal ending is intact, but loss of the C-terminus abrogates both migration and colonization. Our investigations have implications for wound healing but also for bioengineering of skin.