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

We investigated the effect of the neuropeptides vasoactive intestinal peptide (VIP), (D-Phe2)-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.

Synthetic wound dressings--evaluation of interactions with epithelial and dermal cells in vitro.

Comparative testing of seven wound dressings (WD) has been performed with human HaCaT keratinocyte and mouse 3T3 fibroblast cultures. To assess biocompatibility, morphologic examinations were combined with cell counting. Supernatants were subjected to measurements of tissue peptide antigen (TPS), soluble intercellular adhesion molecule 1 (ICAM-1), and interleukins (IL-1 alpha, -1 beta, -6). Furthermore, monoxygenation, the reduced glutathione/oxidized gluthathione (GSH/GSSG) ratio and lipid peroxides were determined. Initial morphologic events were noted within the first day of exposure to WD. After 72 h, inhibition of cell growth was observed in the presence of hydrocolloids and hydrogels. The cytochrome-P-450-dependent ethoxyresorufin 0-deethylation rate and the GSH/GSSG ratio were not altered by WD in HaCaT cells. Lipid peroxide generation, IL-1 and ICAM-1 were scarcely detectable. TPS and IL-6 release indicate the presence of an 'activated stage' of keratinocytes and fibroblasts exposed to WD. Peptide release in vivo may contribute to the beneficial effects of modern dressings in the treatment of superficial cutaneous wounds.