Cong Rui, Deng Chengyu, Li Pengwei, Tang Yiwei, Hou Jinfan, Zhao Jiehui, Wang Qili, Chen Yingying, Tu Jiasheng, Jiang Xiqun, Jiang Lei
State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Nat Commun. 2025 Jul 1;16(1):5797. doi: 10.1038/s41467-025-61141-1.
Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, which remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide (D-CuP) for diabetic wound treatment. The D-CuP is synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (M-CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biological stability against proteases, and broad biological activities. Meanwhile, the hydrogel matrix, exhibiting ROS-scavenging capabilities, has been engineered to be an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrates superior therapeutic efficacy, achieving 97.2% closure of infected wounds.
糖尿病伤口需要在组织再生的同时对微环境进行持续且协调的调节，这仍然是一项重大挑战。作为概念验证，我们在此提议使用二聚体铜肽（D-CuP）来治疗糖尿病伤口。合成D-CuP，然后将其掺入活性氧（ROS）响应水凝胶基质中以提高治疗顺应性，最终形成G/D-CuP制剂。与伤口愈合剂单体铜肽（M-CuP）相比，D-CuP具有多价性、对蛋白酶更强的生物稳定性以及广泛的生物活性。同时，具有ROS清除能力的水凝胶基质已被设计成一种智能药物储库，用于在伤口部位对D-CuP进行伤口响应性释放，同时减轻炎症反应。最终，G/D-CuP组展现出卓越的治疗效果，感染伤口的愈合率达到97.2%。
