Effect of Fibrin-binding Synthetic Oligopeptide on the Healing of Full-thickness Skin Wounds in Streptozotocin-induced Diabetic Rats

Jae-Eun      Chung; Yun-Jeong      Kim; Yoon-Jeong      Park; Ki-Tae      Koo; Yang-Jo      Seol; Yong-Moo      Lee; In-Chul      Rhyu; Young      Ku

doi:10.2174/138161213804805676

Abstract

The aim of this study was to investigate whether topical application of fibrin-binding oligopeptides derived from FN promotes wound healing in streptozotocin (STZ)-induced diabetic rats.

Oligopeptides including fibrin-binding sequences (FF3: CFDKYTGNTYRV, FF5 : CTSRNRCNDQ) of FN repeats were synthesized. Each peptide was loaded in 15 x 15 mm fibrous alginate dressings, and the release kinetics of the peptides was evaluated using trinitrobenzene sulfonic acid for 336 hours.

Two full-thickness cutaneous wounds were prepared on the dorsal skin of each 75 diabetes induced rats. Each wound was divided into FF3-loaded alginate dressing group, FF5-loaded alginate dressing group, alginate dressing group and negative control group. Animals were sacrificed at day 0,3,7 and 14. The wound closure rate, inflammation degree, expression of TGF-β1 and hydroxyproline contents were evaluated.

Both FF3 and FF5 peptides were released rapidly within the first 24 hours. FF3-loaded dressing treated wounds closed significantly faster than other wounds at day 3. And at day 14, FF3- & FF5- loaded dressing treated wounds demonstrated less inflammatory cells infiltration than alginate dressing treated and negative group wounds. TGF-β1 positive cells were more abundant in FF3-, FF5-treated alginate dressing treated wound at day 3 and 14. At last, the hyrdroxyproline contents in the FF3, FF5 group were higher at day 7 and day 14.

Topical application of fibrin-binding domain synthetic oligopeptides from FN resulted in acceleration of full-thickness cutaneous wound healing in diabetic rats.

Keywords: Fibronectin, fibrin-binding domain, diabetes mellitus, full-thickness cutaneous wound, wound healing, oligopeptides, fibrous alginate dressings, FF5 peptides, TGF-β1, diabetic rats