title: Hyaluronate-Epidermal Growth Factor Conjugate for Skin Wound Healing and Regeneration.
abstract: 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.
authors: 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.
authors: Hyemin
authors: H
authors: Kim
authors: 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.
authors: Won Ho
authors: WH
authors: Kong
authors: Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University , 1268-50, Samnangjin-ro, Samnangjin-eup, Miryang, Gyeongnam 50463, Republic of Korea.
authors: Keum-Yong
authors: KY
authors: Seong
authors: Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University , 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.
authors: Dong Kyung
authors: DK
authors: Sung
authors: 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.
authors: Hyeonseon
authors: H
authors: Jeong
authors: 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.
authors: Jin Kon
authors: JK
authors: Kim
authors: Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University , 1268-50, Samnangjin-ro, Samnangjin-eup, Miryang, Gyeongnam 50463, Republic of Korea.
authors: Seung Yun
authors: SY
authors: Yang
authors: 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.
authors: Sei Kwang
authors: SK
authors: Hahn
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D012038:Regeneration / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000648:ultrastructure; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004815:Epidermal Growth Factor; D006820:Hyaluronic Acid