Promoting Angiogenesis in Oxidative Diabetic Wound Microenvironment Using a Nanozyme-Reinforced Self-Protecting Hydrogel
Open Access
- 13 February 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Central Science
- Vol. 5 (3), 477-485
- https://doi.org/10.1021/acscentsci.8b00850
Abstract
Impaired diabetic wound healing represents a devastating and rapidly growing clinical problem associated with high morbidity, mortality, and recurrence rates. Engineering therapeutic angiogenesis in the wounded tissue is critical for successful wound healing. However, stimulating functional angiogenesis of the diabetic wound remains a great challenge, due to the oxidative damage and denaturation of bio-macromolecule-based angiogenic agents in the oxidative diabetic wound microenvironment. Here, we present a unique “seed-and-soil” strategy that circumvents the limitation by simultaneously reshaping the oxidative wound microenvironment into a proregenerative one (the “soil”) and providing proangiogenic miRNA cues (the “seed”) using an miRNA-impregnated, redox-modulatory ceria nanozyme-reinforced self-protecting hydrogel (PCN-miR/Col). The PCN-miR/Col not only reshapes the hostile oxidative wound microenvironment, but also ensures the structural integrity of the encapsulated proangiogenic miRNA in the oxidative microenvironment. Diabetic wounds treated with the PCN-miR/Col demonstrate a remarkably accelerated wound closure and enhanced quality of the healed wound as featured by highly ordered alignment of collagen fiber, skin appendage morphogenesis, functional new blood vessel growth, and oxygen saturation.Keywords
Funding Information
- Ministry of Science and Technology of the People's Republic of China (2016YFA0203600)
- Ministry of Education of the People's Republic of China (520002*172210161)
- National Natural Science Foundation of China (31822019, 51503180, 5161101036, 81620108028)
- Thousand Talents Program for Distinguished Young Scholars (588020*G81501/048)
- Zhejiang Province
This publication has 42 references indexed in Scilit:
- Ceria Nanoparticles that can Protect against Ischemic StrokeAngewandte Chemie, 2012
- Injectable Collagen–Genipin Gel for the Treatment of Spinal Cord Injury: In Vitro StudiesAdvanced Functional Materials, 2011
- Oxidative stress in early diabetic nephropathy: fueling the fireNature Reviews Endocrinology, 2010
- Anti‐inflammatory Properties of Cerium Oxide NanoparticlesSmall, 2009
- Exploiting and antagonizing microRNA regulation for therapeutic and experimental applicationsNature Reviews Genetics, 2009
- Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer ModelCell, 2009
- Isoprostanes Inhibit Vascular Endothelial Growth Factor–Induced Endothelial Cell Migration, Tube Formation, and Cardiac Vessel Sprouting In Vitro, As Well As Angiogenesis In Vivo via Activation of the Thromboxane A 2 ReceptorCirculation Research, 2008
- Inorganic Nanoparticles as Carriers of Nucleic Acids into CellsAngewandte Chemie, 2008
- Interactions between U-937 human macrophages and poly(propyleneimine) dendrimersJournal of Controlled Release, 2007
- Using circular dichroism spectra to estimate protein secondary structureNature Protocols, 2006