The full text of this article hosted at iucr.org is unavailable due to technical difficulties.

Immobilized gradients of epidermal growth factor promote accelerated and directed keratinocyte migration

Tracy Jane Stefonek MS

Department of Biomedical Engineering, University of Wisconsin‐Madison, Madison, Wisconsin

Search for more papers by this author
Kristyn S. Masters PhD

Department of Biomedical Engineering, University of Wisconsin‐Madison, Madison, Wisconsin

Search for more papers by this author
First published: 03 October 2007
Cited by: 34
Reprint requests:
Kristyn S. Masters, PhD, Department of Biomedical Engineering, University of Wisconsin‐Madison, 1550 Engineering Drive, #2152, Madison, WI 53706.
Tel: +1 608 265 4052
Fax: +1 608 265 9239
Email: kmasters@wisc.edu

ABSTRACT

Acceleration of wound closure results not only in decreased patient suffering and cost of wound treatment, but may also minimize scarring and lead to formation of a more stable closed wound. Cell migration is a critical element in wound healing, and it is believed that the ability to control the migration direction of cells will lead to accelerated closure of wounds. Thus, we have synthesized surfaces that are covalently modified with gradients of epidermal growth factor (EGF), a key molecule in the native wound‐healing process, in order to create a platform that promotes directed cell migration. Standard photo‐patterning techniques used herein enabled precise control over the spatial location of tethered EGF and the fabrication and quantitative characterization of gradient patterns of different types and slopes. Under serum‐free conditions, human epidermal keratinocytes on immobilized EGF gradients preferentially migrated in the direction of higher EGF concentrations, and exhibited unidirectional migration speed and distance that was over five‐fold greater than that observed on control surfaces. Treatment of migrating cells with an inhibitor of the EGF receptor resulted in immediate cessation of migration, thus verifying that the observed migration trends were directly attributable to keratinocyte interactions with immobilized EGF.

Number of times cited: 34

  • , 4.19 Growth Factors and Protein-Modified Surfaces and Interfaces ☆, Comprehensive Biomaterials II, 10.1016/B978-0-12-803581-8.10191-2, (321-359), (2017).
  • , Evaluation of a bilayered, micropatterned hydrogel dressing for full-thickness wound healing, Experimental Biology and Medicine, 241, 9, (986), (2016).
  • , Growth factor conjugation: Strategies and applications, Journal of Biomedical Materials Research Part A, 103, 2, (819-838), (2014).
  • , Opposing Rigidity-Protein Gradients Reverse Fibroblast Durotaxis, ACS Biomaterials Science & Engineering, 10.1021/acsbiomaterials.5b00229, 1, 8, (621-631), (2015).
  • , Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche, Integrative Biology, 10.1039/C4IB00152D, 7, 1, (101-111), (2015).
  • , Surface Density of Vascular Endothelial Growth Factor Modulates Endothelial Proliferation and Differentiation, Journal of Cellular Biochemistry, 115, 1, (111-120), (2013).
  • , Engineering Biomolecular Microenvironments for Cell Instructive Biomaterials, Advanced Healthcare Materials, 3, 6, (797-810), (2014).
  • , Epidermal Growth Factor–Functionalized Polymeric Multilayer Films: Interplay between Spatial Location and Bioavailability of EGF, Journal of Investigative Dermatology, 134, 6, (1757), (2014).
  • , Controlled release and gradient formation of human glial-cell derived neurotrophic factor from heparinated poly(ethylene glycol) microsphere-based scaffolds, Biomaterials, 10.1016/j.biomaterials.2014.04.027, 35, 24, (6473-6481), (2014).
  • , Cell Surface Epidermal Growth Factor Receptors Increase Src and c-Cbl Activity and Receptor Ubiquitylation, Journal of Biological Chemistry, 10.1074/jbc.M114.579581, 289, 37, (25537-25545), (2014).
  • , The use of native chemical functional groups presented by wound beds for the covalent attachment of polymeric microcarriers of bioactive factors, Biomaterials, 34, 2, (340), (2013).
  • , Delivering bioactive molecules as instructive cues to engineered tissues, Expert Opinion on Drug Delivery, 10.1517/17425247.2012.668521, 9, 4, (473-492), (2012).
  • , Bioactive Self‐Assembled Monolayer Gradients, Soft Matter Gradient Surfaces, (329-363), (2012).
  • , Covalent Growth Factor Immobilization Strategies for Tissue Repair and Regeneration, Macromolecular Bioscience, 11, 9, (1149-1163), (2011).
  • , Growth Factors and Protein-Modified Surfaces and Interfaces, Comprehensive Biomaterials, 10.1016/B978-0-08-055294-1.00263-4, (247-279), (2011).
  • , Immune responses to implants – A review of the implications for the design of immunomodulatory biomaterials, Biomaterials, 10.1016/j.biomaterials.2011.05.078, 32, 28, (6692-6709), (2011).
  • , Spatially directed guidance of stem cell population migration by immobilized patterns of growth factors, Biomaterials, 10.1016/j.biomaterials.2010.12.005, 32, 11, (2775-2785), (2011).
  • , Bioactivity of immobilized EGF on self‐assembled monolayers: Optimization of the immobilization process, Journal of Biomedical Materials Research Part A, 94A, 2, (576-585), (2010).
  • , The use of immobilized osteogenic growth peptide on gradient substrates synthesized via click chemistry to enhance MC3T3-E1 osteoblast proliferation, Biomaterials, 31, 7, (1604), (2010).
  • , Biomedical Applications of Photochemistry, Tissue Engineering Part B: Reviews, 10.1089/ten.teb.2009.0797, 16, 5, (509-522), (2010).
  • , Fructose-1,6-bisphosphate aldolase A is involved in HaCaT cell migration by inducing lamellipodia formation, Journal of Dermatological Science, 58, 2, (123), (2010).
  • , Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC, Journal of Biomedicine and Biotechnology, 10.1155/2010/795385, 2010, (1-10), (2010).
  • , Fabrication of Density Gradients of Biodegradable Polymer Microparticles and Their Use in Guiding Neurite Outgrowth, Advanced Functional Materials, 20, 10, (1632-1637), (2010).
  • , Regulation of keratinocyte signaling and function via changes in epidermal growth factor presentation, Acta Biomaterialia, 6, 9, (3415), (2010).
  • , Endothelial cell‐specific molecule 2 (ECSM2) modulates actin remodeling and epidermal growth factor receptor signaling, Genes to Cells, 14, 3, (281-293), (2009).
  • , Biomimetic strategies based on viruses and bacteria for the development of immune evasive biomaterials, Biomaterials, 10.1016/j.biomaterials.2008.11.025, 30, 11, (1989-2005), (2009).
  • , Escherichia coli expression and refolding of E/K-coil-tagged EGF generates fully bioactive EGF for diverse applications, Protein Expression and Purification, 64, 2, (108), (2009).
  • , PEG Hydrogels for the Controlled Release of Biomolecules in Regenerative Medicine, Pharmaceutical Research, 10.1007/s11095-008-9801-2, 26, 3, (631-643), (2008).
  • 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society Minneapolis, MN 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE , (2009). Regulation of cell signaling and function via changes in growth factor presentation , (2009). 1167 1171 5332607 , 10.1109/IEMBS.2009.5332607 http://ieeexplore.ieee.org/document/5332607/
  • , Structure-based targeting of bioactive proteins into cypovirus polyhedra and application to immobilized cytokines for mammalian cell culture, Biomaterials, 30, 26, (4297), (2009).
  • , Anti‐apoptotic role of EGF in HaCaT keratinocytes via a PPARβ‐dependent mechanism, Wound Repair and Regeneration, 16, 5, (691-698), (2008).
  • , Co-Immobilization of Gradient-Patterned Growth Factors for Directed Cell Migration, Annals of Biomedical Engineering, 36, 12, (2121), (2008).
  • , Functionalized silk fibers from transgenic silkworms for wound healing applications: Surface presentation of bioactive epidermal growth factor, Journal of Biomedical Materials Research Part A, , (2018).
  • , Spatial Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis, International Journal of Molecular Sciences, 10.3390/ijms14010072, 14, 1, (72-87), (2012).