Synergistic effects of hyaluronate - epidermal growth factor conjugate patch on chronic wound healing.

The proteolytic microenvironment in the wound area reduces the stability and the half-life of growth factors in vivo， making difficult the topical delivery of growth factors. Here， epidermal growth factor (EGF) was conjugated to hyaluronate (HA) to improve the long-term stability against enzymatic degradation and the therapeutic effect by enhancing the biological interaction with HA receptors on skin cells. After the synthesis of HA-EGF conjugates， they were incorporated into a patch-type formulation for the facile topical application and sustained release of EGF. According to ELISA， the HA-EGF conjugates showed a long-term stability compared with native EGF. Furthermore， HA-EGF conjugates appeared to interact with skin cells through two types of HA and EGF receptors， resulting in a synergistically improved healing effect. Taken together， we could confirm the feasibility of HA-EGF conjugates for the transdermal treatment of chronic wounds.