title: Vitronectin: growth factor complexes hold potential as a wound therapy approach.
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 alpha(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.
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia. z.upton@qut.edu.au
authors.forename: Zee
authors.initials: Z
authors.lastname: Upton
authors.forename: Leila
authors.initials: L
authors.lastname: Cuttle
authors.forename: Anthony
authors.initials: A
authors.lastname: Noble
authors.forename: Margit
authors.initials: M
authors.lastname: Kempf
authors.forename: Gemma
authors.initials: G
authors.lastname: Topping
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.forename: Julie
authors.initials: J
authors.lastname: Mill
authors.forename: Damien G
authors.initials: DG
authors.lastname: Harkin
authors.forename: Olena
authors.initials: O
authors.lastname: Kravchuk
authors.forename: David I
authors.initials: DI
authors.lastname: Leavesley
authors.forename: Roy M
authors.initials: RM
authors.lastname: Kimble
mesh_terms: D000818:Animals; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D012867:Skin / Q000196:embryology / Q000378:metabolism; D013552:Swine; D019096:Vitronectin / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D039564:Integrin alphaV; D036341:Intercellular Signaling Peptides and Proteins; D019096:Vitronectin