机构:[1]Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China.[2]School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China.[3]Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan 650504, China.[4]Department of Endocrinology, Affiliated Hospital of Yunnan University, Kunming, Yunnan 650021, China.[5]Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650500, China内科科室皮肤科昆明医科大学附属第一医院
The combined use of peptides, nanomaterials, and hydrogels is a promising strategy for chronic skin wound healing, which remains a huge clinical challenge. Here, we optimized the RL-QN15 peptide, which was shown to be a pro-healing drug candidate in our previous research, to obtain the cyclic heptapeptide (CyRL-QN15) with considerable therapeutic potency against skin wounds. Furthermore, a Zn2+-crosslinked sodium alginate (ZA) hydrogel containing hollow polydopamine (HPDA) nanoparticles loaded with CyRL-QN15 (HPDAlCyRL-QN15/ZA hydrogel) was prepared and characterized, which significantly enhanced the pro-healing potency of CyRL-QN15. At the cellular level, this nontoxic hydrogel accelerated the proliferation, migration, tube formation, and scratch healing of skin cells, regulated the secretion of cytokines from macrophages, directly scavenged free radicals, and decreased reactive oxygen species. Moreover, the HPDAlCyRL-QN15/ZA hydrogel significantly accelerated the healing of full-thickness skin wounds in type 2 diabetic mice by promoting the transition of macrophages to the M2 phenotype to reduce inflammation and cause re-epithelialization, formation of granulation tissue, deposition of collagen, and angiogenesis. Of note, the hydrogel also facilitated wound healing of diabetic patient skin cultured ex vivo. Overall, the HPDAlCyRL-QN15/ZA hydrogel presents a novel therapeutic strategy for clinical chronic skin wound (diabetic ulcer) healing.
基金:
This work was supported by grants from the National Natural Science
Foundation of China (32060212, 81760648, and 82160159); Program for
Innovative Research Team in the Ministry of Education of China (IRT17-R49);Major Science and Technology Project of Yunnan Province (202202AA100004);
Key project from Yunnan Key Laboratory of Pharmacology for Natural Products
(YKLPNP-K2301); Science and Technology Leadership Talent Project in Yunnan,
China (2017HA010); Key Project of Yunnan Applied Basic Research Project-
Kunming Medical University Union Foundation (202101AY070001-006);
Yunnan Applied Basic Research Project Foundation (2019FB128); Project of
Yunnan Applied Basic Research Project-Kunming Medical University Union
Foundation (202101AY070001-036); and Innovative Team of Precise Prevention
and Treatment against Metabolic Diseases of Yunnan University.
第一作者机构:[1]Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China.
共同第一作者:
通讯作者:
通讯机构:[1]Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China.[2]School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China.
推荐引用方式(GB/T 7714):
Fu Zhe,Sun Huiling,Wu Yutong,et al.A cyclic heptapeptide-based hydrogel boosts the healing of chronic skin wounds in diabetic mice and patients[J].NPG ASIA MATERIALS.2022,14(1):doi:10.1038/s41427-022-00444-x.
APA:
Fu, Zhe,Sun, Huiling,Wu, Yutong,Li, Chao,Wang, Yinglei...&Yang, Xinwang.(2022).A cyclic heptapeptide-based hydrogel boosts the healing of chronic skin wounds in diabetic mice and patients.NPG ASIA MATERIALS,14,(1)
MLA:
Fu, Zhe,et al."A cyclic heptapeptide-based hydrogel boosts the healing of chronic skin wounds in diabetic mice and patients".NPG ASIA MATERIALS 14..1(2022)