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Vitronectin : growth factor complexes hold potential as a wound therapy approach

Upton, Zee, Cuttle, Leila, Noble, Anthony M., Kempf, Margit, Topping, Gemma L., Malda, Jos, Xie, Yan, Mill, Julie, Harkin, Damien G., Kravchuk, Olena, Leavesley, David I., & Kimble, Roy M. (2008) Vitronectin : growth factor complexes hold potential as a wound therapy approach. Journal of Investigative Dermatology, 128(6), pp. 1535-1544.

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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 alphav 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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27 citations in Scopus
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26 citations in Web of Science®

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ID Code: 13019
Item Type: Journal Article
Additional Information: For more information, please refer to the journal's website (see hypertext link) or contact the author.
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Keywords: chronic wound fluid, wound healing, burn, extracellular matrix, epidermal, human skin, skin, tissue, cells and tissue, tissue repair and regeneration, tissue repair, burns research, vitronectin
DOI: 10.1038/sj.jid.5701148
ISSN: 0022-202X
Subjects: Australian and New Zealand Standard Research Classification > TECHNOLOGY (100000) > MEDICAL BIOTECHNOLOGY (100400) > Medical Biotechnology not elsewhere classified (100499)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100) > Medical Biochemistry and Metabolomics not elsewhere classified (110199)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2008 Society for Investigative Dermatology
Deposited On: 17 Mar 2008
Last Modified: 05 Mar 2014 15:19

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