title: Controlled release of epidermal growth factor from hydrogels accelerates wound healing in diabetic rats.
abstract: BACKGROUND
  We sought to develop new recombinant human epidermal growth factor (rhEGF)-containing hydrogels and to investigate their biological activity and therapeutic effects on wound healing in diabetic rats.
  
  
  METHODS
  Levels of rhEGF released from hydrogels were measured by enzyme-linked immunosorbent assay. The cellular proliferating activity of released rhEGF was evaluated by MTT assay. Fifty-six wounded diabetic rats were randomly divided into four groups with different topical treatment daily. The therapeutic effects were evaluated by wound area measurement, histologic analysis, immunohistochemical assessment of proliferating cell nuclear antigen and B-cell lymphoma/leukemia-2, and Western blotting of EGF receptor.
  
  
  RESULTS
  The rhEGF released from the hydrogel matrix kept its bioactivity on stimulating proliferation of the BALB/c3T3 cell line. Wound closure rates on postoperative day 14 were 75.8% in the negative control group, 82.83% in the group treated with hydrogel matrix, 85.87% in the group treated with rhEGF-containing hydrogel, and 81.18% in the group treated with rhEGF solution. Compared with hydrogel matrix, rhEGF-containing hydrogel had an additional effect on induction of EGF receptor expression (P < .05). Compared with negative controls, protein expression of B-cell lymphoma/leukemia-2 was higher in the rhEGF-containing groups (P < .05). Proliferating cell nuclear antigen was induced at its highest level on day 7 in the rhEGF-containing hydrogel-treated group (P < .05).
  
  
  CONCLUSIONS
  These data from in vitro release and diabetic animal models highlight the efficacy of hydrogels as a controlled releasing system for topical application of EGFs. The rhEGF-containing hydrogel we developed holds the merits of prolonged and sustained releasing of bioactive rhEGF and therapeutic potential in enhancing diabetic wound healing.
authors.affiliation: Department of Endocrinology and Metabolism, The Second Affiliated Hospital, SUN Yat-sen University, Guangzhou, China.
authors.forename: Guojuan
authors.initials: G
authors.lastname: Lao
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.forename: Shaoling
authors.initials: S
authors.lastname: Zhang
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins; D014945:Wound Healing
chemical_list: D020100:Hydrogels; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor