Nonhealing chronic wounds on foot induced by diabetes is a complicated pathologic process. They are mainly caused by impaired neovascularization, neuropathy, and excessive inflammation. A strategy, which can accelerate the vessel network formation as well as inhibit inflammatory response at the same time, makes it possible for effective diabetic ulcers treatment. Co-delivery of multiple drugs with complementary bioactivity offers a strategy to properly treat diabetic wound. We previously demonstrated that hydroxysafflor yellow A (HSYA) could accelerate diabetic wound healing through promoting angiogenesis and reducing inflammatory response. In order to further enhance blood vessel formation, a pro-angiogenic molecular called deferoxamine (DFO) was topically co-administrated with HSYA. The in vitro results showed that the combination of DFO and HSYA exerted synergistic effect on enhancing angiogenesis by upregulation of hypoxia inducible factor-1 alpha (HIF-1α) expression. The interpenetrating polymer networks hydrogels, characterized by good breathability and water absorption, were designed for co-loading of DFO and HSYA aiming to recruit angiogenesis relative cells and upgrade wound healing in vivo. Both DFO and HSYA in hydrogel have achieved sustained release. The in vivo studies indicated that HSYA/DFO hydrogel could accelerate diabetic wound healing. With a high expression of Hif-1α which is similar to that of normal tissue. The noninvasive US/PA imaging revealed that the wound could be recovered completely with abundant blood perfusion in dermis after given HSYA/DFO hydrogel for 28 days. In conclusion, combination of pro-angiogenic small molecule DFO and HSYA in hydrogel provides a promising strategy to productively promote diabetic wound healing as well as better the repair quality.

中文翻译：

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联合递送去铁胺和羟基红花黄 A 通过增强血管生成来加速糖尿病伤口愈合。

糖尿病引起的足部慢性伤口不愈合是一个复杂的病理过程。它们主要是由新生血管受损、神经病变和过度炎症引起的。一种可以加速血管网络形成并同时抑制炎症反应的策略，使得有效的糖尿病溃疡治疗成为可能。具有互补生物活性的多种药物的共同递送提供了正确治疗糖尿病伤口的策略。我们之前证明，羟基红花黄 A (HSYA) 可以通过促进血管生成和减少炎症反应来加速糖尿病伤口愈合。为了进一步增强血管形成，一种称为去铁胺 (DFO) 的促血管生成分子与 HSYA 局部联合给药。体外结果表明，DFO和HSYA联合通过上调缺氧诱导因子-1α（HIF-1α）表达，对增强血管生成发挥协同作用。互穿聚合物网络水凝胶具有良好的透气性和吸水性，被设计用于共同负载DFO和HSYA，旨在招募血管生成相关细胞并促进体内伤口愈合。水凝胶中的DFO和HSYA均实现了缓释。体内研究表明HSYA/DFO水凝胶可以加速糖尿病伤口愈合。Hif-1α高表达，与正常组织相似。无创US/PA成像显示，给予HSYA/DFO水凝胶28天后，伤口可以完全恢复，真皮内有充足的血液灌注。总之，在水凝胶中结合促血管生成小分子 DFO 和 HSYA 提供了一种有前景的策略，可以有效促进糖尿病伤口愈合并提高修复质量。