A Combination Therapy Using Electrical Stimulation and Adaptive, Conductive Hydrogels Loaded with Self‐Assembled Nanogels Incorporating Short Interfering RNA Promotes the Repair of Diabetic Chronic Wounds. Issue 30 (5th September 2022)

• Record Type: Journal Article
• Authors: Lei, Huan; Fan, Daidi
• Is Part Of: Advanced science. Volume 9:Issue 30(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-05
• Subjects: diabetic chronic wounds -- hydrogel‐ES combination therapy -- self‐assembled nanogels -- siRNA delivery; Science -- Periodicals; 505
• DOI: 10.1002/advs.202201425
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: In addition to oxidative stress and impaired angiogenesis, the overexpression of metalloproteinases (MMPs) and proinflammatory cytokines, which are promoted by hyperglycemia, causes chronic inflammation in diabetic wounds. Herein, TA‐siRNA nanogels are prepared for the first time on the basis of the self‐assembling interaction between tannic acid (TA) and short interfering RNA (siRNA). The efficient, biodegradable nanogels are cross‐linked with poly(vinyl alcohol) (PVA), human‐like collagen (HLC), TA, and borax to prepare adaptive, conductive PHTB (TA‐siRNA) hydrogels. In response to high levels of reactive oxygen species (ROS), the ROS‐responsive borate ester bonds in the hydrogels are oxidized and broken, and TA‐siRNA nanogels are released into cells to reduce the expression of the MMP‐9. Moreover, the TA and HLC promote collagen expression, reduce inflammation, and ROS level. It is found that electrical stimulation (ES) promotes the in vivo release of TA‐siRNA nanogels from PHTB (TA‐siRNA) hydrogels and endocytosis of the nanogels. The combination therapy using ES and PHTB (TA‐siRNA) hydrogels accelerates the healing of diabetic wounds by reducing the levels of ROS and MMP‐9 and promoting the polarization of macrophages, production of collagen, and angiogenesis. This study provides insights on the design of functional gene‐delivery and efficient therapeutic strategies to promote the repair of diabetic chronic wounds. Abstract : The efficient, nontoxic, biodegradable self‐assembled tannic acid‐short interfering RNA (TA‐siRNA) nanogels could promote the effective cellular internalization of siRNA to reduce the expression of the target gene. Adaptive conductive hydrogels combined with electrical stimulation (ES) could promote the repair of diabetic chronic wounds by scavenging reactive oxygen species (ROS), metalloproteinases‐9 (MMP‐9), and proinflammatory factors and promoting macrophage polarization and vascularization.