Vitronectin: growth factor complexes hold potential as a wound therapy approach
Date
2008
Authors
Upton, Z.
Cuttle, L.
Noble, A.
Kempf, M.
Topping, G.
Malda, J.
Xie, Y.
Mill, J.
Harkin, D.
Kravchuk, O.
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Journal Title
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Type:
Journal article
Citation
Journal of Investigative Dermatology, 2008; 128(6):1535-1544
Statement of Responsibility
Zee Upton, Leila Cuttle, Anthony Noble, Margit Kempf, Gemma Topping, Jos Malda, Yan Xie, Julie Mill, Damien G Harkin, Olena Kravchuk, David I Leavesley and Roy M Kimble
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Abstract
Topical administration of growth factors has displayed some potential in wound healing, but variable efficacy, high doses, and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple growth factors and extracellular matrix (ECM) proteins. We report herein that complexes comprising IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes in two- and three-dimensional in vitro cell models and are active, even in the presence of wound fluid. Moreover, these responses require activation of both the IGF receptor and the VN-binding av integrins. Further, we assessed the complexes as a topical agent in the treatment of deep dermal partial thickness burns in a porcine model. This pilot study revealed that the complexes may hold promise as a wound healing therapy. Critically, the significant responses observed in vitro and the encouraging preliminary data in vivo were obtained with nanogram doses of growth factors. This suggests that coupling delivery of growth factors to ECM proteins such as VN may ultimately prove to be a more effective strategy for developing a wound healing therapy.
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Copyright 2008 The Society for Investigative Dermatology