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A new future for growth factor complexes as wound therapies?

Leavesley, David & Upton, Zee (2010) A new future for growth factor complexes as wound therapies? In Sen, Chandon (Ed.) Advances in Wound Care. Mary Ann Liebert, Inc., New Rochelle, New York, pp. 155-160.

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          Abstract

          Background: Topical administration of growth factors (GFs) 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 GFs and extracellular matrix (ECM) proteins.

          The Problem: Deep dermal partial thickness burn (DDPTB) injuries are the most common burn presentation to pediatric hospitals and also represent the most difficult burn injury to manage clinically. DDPTB often repair with a hypertrophic scar. Wounds that close rapidly exhibit reduced scarring. Thus treatments that shorten the time taken to close DDTPB’s may coincidently reduce scarring.

          Basic/Clinical Science Advances: We have observed that multi-protein complexes comprised of IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes. These responses require activation of both the IGF-1R and the VN-binding αv integrins. We have recently evaluated the wound healing potential of these GF:VN complexes in a porcine model of DDTPB injury.

          Clinical Care Relevance: This pilot study demonstrates that GF:VN complexes hold promise as a wound healing therapy. Enhanced healing responses were observed after treatment with nanogram doses of the GF:VN complexes in vitro and in vivo. Critically healing was achieved using substantially less GF than studies in which GFs alone have been used.

          Conclusion: These data suggest that coupling GFs to ECM proteins, such as VN, may ultimately prove to be an improved technique for the delivery of novel GF-based wound therapies.

          Impact and interest:

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          ID Code: 33705
          Item Type: Book Chapter
          Additional Information: The authors wish to acknowledge Carolyn Hyde, Sarah Tilley, Brett Hollier, Christopher Towne, Jennifer Kricker, Leila Cuttle, Anthony Noble, Margit Kempf, Gemma Topping, Jos Malda, Yan Xie, Julie Mill, Damien G. Harkin, Olena Kravchuk, and Roy M. Kimble for their invaluable contributions to this research. The work described in this work has been funded by awards from the National Health and Medical Research Council (NHMRC) of Australia, Australian Research Council (ARC), Juvenile Diabetes Research Trust (Australia), Tissue Therapies Ltd and Queensland Smart State Fellowship (ZU). The authors have purchased shares in Tissue Therapies Ltd., the Australian biotechnology company spun out from the Queensland University of Technology (patent holder) to commercialise this technology. The authors provide consultant scientific services to Tissue Therapies Ltd. This work is solely that of the listed authors.
          Keywords: Vitronectin, Extracellular Matrix, Multi-protein complexes, Wound Healing
          DOI: 10.1089/awc.2010.0243
          ISBN: 9781934854013
          Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
          Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cellular Interactions (incl. Adhesion Matrix Cell Wall) (060106)
          Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Dermatology (110304)
          Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL PHYSIOLOGY (111600) > Cell Physiology (111601)
          Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL PHYSIOLOGY (111600) > Systems Physiology (111603)
          Divisions: Past > Schools > Cell & Molecular Biosciences
          Past > QUT Faculties & Divisions > Faculty of Science and Technology
          Current > Institutes > Institute of Health and Biomedical Innovation
          Copyright Owner: Copyright 2010 Mary Ann Liebert, Inc.
          Deposited On: 15 Dec 2010 10:57
          Last Modified: 15 Sep 2011 12:13

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