Vitronectin: Growth Factor Complexes Hold Potential as a Wound Therapy Approach

Upton, Zee, Cuttle, Leila, Noble, Anthony, Kempf, Margit, Topping, Gemma, Malda, Jos, Xie, Yan, Mill, Julie, Harkin, Damien G., Kravchuk, Olena, Leavesley, David I. and Kimble, Roy M. (2008) Vitronectin: Growth Factor Complexes Hold Potential as a Wound Therapy Approach. Journal of Investigative Dermatology, 128 1: 1535-1544. doi:10.1038/sj.jid.5701148


Author Upton, Zee
Cuttle, Leila
Noble, Anthony
Kempf, Margit
Topping, Gemma
Malda, Jos
Xie, Yan
Mill, Julie
Harkin, Damien G.
Kravchuk, Olena
Leavesley, David I.
Kimble, Roy M.
Title Vitronectin: Growth Factor Complexes Hold Potential as a Wound Therapy Approach
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
Publication date 2008-01-17
Year available 2008
Sub-type Article (original research)
DOI 10.1038/sj.jid.5701148
Open Access Status
Volume 128
Issue 1
Start page 1535
End page 1544
Total pages 10
Editor L. Goldsmith
Place of publication UK
Publisher Nature Publishing Group
Language eng
Subject 320503 Clinical Pharmacology and Therapeutics
329903 Therapies and Therapeutic Technology
C1
730109 Surgical methods and procedures
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 v 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.
Keyword Dermatology
Dermatology
DERMATOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Thu, 06 Mar 2008, 02:45:26 EST