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.

中文翻译：

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透明质酸-表皮生长因子结合物贴剂对慢性伤口愈合的协同作用

伤口区域的蛋白水解微环境降低了体内生长因子的稳定性和半衰期，使生长因子的局部递送变得困难。在这里，表皮生长因子（EGF）与透明质酸盐（HA）结合，通过增强与皮肤细胞上HA受体的生物相互作用来提高抗酶促降解的长期稳定性和治疗效果。合成HA–EGF共轭物后，将其掺入贴剂型制剂中，以方便局部应用和EGF的持续释放。根据ELISA，与天然EGF相比，HA–EGF结合物显示出长期稳定性。此外，HA–EGF结合物似乎通过两种类型的HA和EGF受体与皮肤细胞相互作用，从而产生协同改善的愈合效果。两者合计，我们可以证实HA–EGF偶联物在慢性伤口经皮治疗中的可行性。