Controlled delivery of heparin-binding EGF-like growth factor yields fast and comprehensive wound healing

• Published in: Journal of controlled release Vol. 166; no. 2; pp. 124 - 129
• Main Authors: Johnson, Noah Ray, Wang, Yadong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.03.2013
• Subjects: adverse effects; Angiogenesis; Animals; Cell Movement; Cell Proliferation - drug effects; Cells, Cultured; Coacervate; Delayed-Action Preparations; epidermal growth factor; granulation tissue; Granulation Tissue - drug effects; Growth factors; Heparin; Heparin-binding EGF-like Growth Factor; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - administration & dosage; Intercellular Signaling Peptides and Proteins - therapeutic use; keratinocytes; Keratinocytes - drug effects; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Microscopy, Fluorescence; Neovascularization, Physiologic - drug effects; Polycation; therapeutics; tissue repair; Wound healing; Wound Healing - drug effects; Wounds and Injuries - pathology; Coacervate; Wound healing; Polycation; Heparin; Growth factors
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.11.004

Wound healing is a dynamic process that relies on coordinated signaling molecules to succeed. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is proven to accelerate healing, however precise control over its application is necessary to reduce side effects and achieve desired therapeutic benefit. To achieve effective growth factor delivery we designed a bioactive heparin-based coacervate. In vitro, HB-EGF released from the coacervate delivery system displayed enhanced bioactivity and promoted human keratinocyte migration while preserving cell proliferative capability. In a mouse excisional full-thickness wound model, controlled release of HB-EGF within the wound significantly accelerated wound closure more effectively than an equal dosage of free HB-EGF. Healing was induced by rapid re-epithelialization, granulation tissue formation, and accompanied by angiogenesis. Consistent with in vitro results, wounds treated with HB-EGF coacervate exhibited enhanced migration of keratinocytes with retained proliferative potential, forming a confluent layer for regained barrier function within 7days. Collectively, these results suggest that coacervate-based controlled release of HB-EGF may serve as a new therapy to accelerate healing of cutaneous wounds. [Display omitted]