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Biomacromolecules. 2016 Nov 14;17(11):3694-3705. Epub 2016 Nov 3.

Hyaluronate-Epidermal Growth Factor Conjugate for Skin Wound Healing and Regeneration.

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Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea.
Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University , 1268-50, Samnangjin-ro, Samnangjin-eup, Miryang, Gyeongnam 50463, Republic of Korea.
Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University , 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.
National Creative Research Initiative Center for Smart Block Copolymers, Department of Chemical Engineering, POSTECH , 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea.


Epidermal growth factor (EGF) has been recognized as an excellent wound healing agent due to its therapeutic function stimulating skin cell growth, proliferation and differentiation. However, the transdermal delivery of EGF poses a significant challenge due to its short half-life and lack of efficient formulation. Here, to improve the transdermal delivery efficiency, EGF was conjugated to hyaluronate (HA), which was formulated into a patch-type film for skin wound healing. HA-EGF conjugate was synthesized by coupling reaction between aldehyde-modified HA and N-terminal amine group of EGF to minimize the loss of biological activities. The HA-EGF conjugates exhibited similar biological activities with native EGF as confirmed by ELISA and proliferation tests using murine and human fibroblasts. For the efficient topical delivery, HA-EGF conjugates were incorporated into a matrix film of high molecular weight HA. Two-photon microscopy clearly visualized more efficient transdermal delivery of HA-EGF conjugates to both normal skin and peripheral tissues around the wound area rather than that of EGF. Optical imaging and ELISA after in vivo transdermal delivery showed that the conjugation of EGF to HA retarded its degradation and extended its residence time in the wound area. Furthermore, in vivo transdermal delivery of HA-EGF conjugate in the patch-type HA film resulted in significantly improved regeneration of skin tissues even into hypodermis.

[Indexed for MEDLINE]

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