Multistage ROS-Responsive and Natural Polyphenol-Driven Prodrug Hydrogels for Diabetic Wound Healing

The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticl...

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Published inACS applied materials & interfaces Vol. 14; no. 47; pp. 52643 - 52658
Main Authors Ni, Zhipeng, Yu, Haojie, Wang, Li, Huang, Yudi, Lu, Hui, Zhou, Haiying, Liu, Qingxian
Format Journal Article
LanguageEnglish
Published American Chemical Society 30.11.2022
Subjects
Biological and Medical Applications of Materials and Interfaces
prodrug
diabetic wound
anti-inflammation
ROS-responsive
polyphosphazene
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Abstract The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticle hydrogels (PPBA-TA-PVA) can be obtained by conveniently mixing TA, phenylboric acid modified polyphosphazene (PPBA), and poly­(vinyl alcohol) (PVA). The obtained PPBA-TA-PVA hydrogels could effectively inhibit the growth of Escherichia coli (antibacterial rate = 93.1 ± 1.1%) within 4 h and effectively scavenge both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and •OH radicals in vitro. Besides, the cell migration rate of HDFa cells treated with PPBA-TA-PVA hydrogels (84.2 ± 4.6%) was twice the rate of normal cells (43.8 ± 8.1%) after 24 h of cocultivation. The clinical relevance was demonstrated further by assessing the PPBA-TA-PVA hydrogels in full-thickness excisional wounds in a streptozotocin (STZ)-induced diabetic rat model. The PPBA-TA-PVA hydrogels could act as effective ROS-scavenging agents to alleviate inflammation and accelerate wound closure by decreasing the proinflammatory cytokines (IL-6, IL-1β) and increasing the gene expression of TGF-β1, COL-1, and COL-3, which resulted in faster re-epithelialization and increased formation of granulation tissue.
AbstractList The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticle hydrogels (PPBA-TA-PVA) can be obtained by conveniently mixing TA, phenylboric acid modified polyphosphazene (PPBA), and poly(vinyl alcohol) (PVA). The obtained PPBA-TA-PVA hydrogels could effectively inhibit the growth of Escherichia coli (antibacterial rate = 93.1 ± 1.1%) within 4 h and effectively scavenge both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and •OH radicals in vitro. Besides, the cell migration rate of HDFa cells treated with PPBA-TA-PVA hydrogels (84.2 ± 4.6%) was twice the rate of normal cells (43.8 ± 8.1%) after 24 h of cocultivation. The clinical relevance was demonstrated further by assessing the PPBA-TA-PVA hydrogels in full-thickness excisional wounds in a streptozotocin (STZ)-induced diabetic rat model. The PPBA-TA-PVA hydrogels could act as effective ROS-scavenging agents to alleviate inflammation and accelerate wound closure by decreasing the proinflammatory cytokines (IL-6, IL-1β) and increasing the gene expression of TGF-β1, COL-1, and COL-3, which resulted in faster re-epithelialization and increased formation of granulation tissue.The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticle hydrogels (PPBA-TA-PVA) can be obtained by conveniently mixing TA, phenylboric acid modified polyphosphazene (PPBA), and poly(vinyl alcohol) (PVA). The obtained PPBA-TA-PVA hydrogels could effectively inhibit the growth of Escherichia coli (antibacterial rate = 93.1 ± 1.1%) within 4 h and effectively scavenge both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and •OH radicals in vitro. Besides, the cell migration rate of HDFa cells treated with PPBA-TA-PVA hydrogels (84.2 ± 4.6%) was twice the rate of normal cells (43.8 ± 8.1%) after 24 h of cocultivation. The clinical relevance was demonstrated further by assessing the PPBA-TA-PVA hydrogels in full-thickness excisional wounds in a streptozotocin (STZ)-induced diabetic rat model. The PPBA-TA-PVA hydrogels could act as effective ROS-scavenging agents to alleviate inflammation and accelerate wound closure by decreasing the proinflammatory cytokines (IL-6, IL-1β) and increasing the gene expression of TGF-β1, COL-1, and COL-3, which resulted in faster re-epithelialization and increased formation of granulation tissue.
The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticle hydrogels (PPBA-TA-PVA) can be obtained by conveniently mixing TA, phenylboric acid modified polyphosphazene (PPBA), and poly­(vinyl alcohol) (PVA). The obtained PPBA-TA-PVA hydrogels could effectively inhibit the growth of Escherichia coli (antibacterial rate = 93.1 ± 1.1%) within 4 h and effectively scavenge both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and •OH radicals in vitro. Besides, the cell migration rate of HDFa cells treated with PPBA-TA-PVA hydrogels (84.2 ± 4.6%) was twice the rate of normal cells (43.8 ± 8.1%) after 24 h of cocultivation. The clinical relevance was demonstrated further by assessing the PPBA-TA-PVA hydrogels in full-thickness excisional wounds in a streptozotocin (STZ)-induced diabetic rat model. The PPBA-TA-PVA hydrogels could act as effective ROS-scavenging agents to alleviate inflammation and accelerate wound closure by decreasing the proinflammatory cytokines (IL-6, IL-1β) and increasing the gene expression of TGF-β1, COL-1, and COL-3, which resulted in faster re-epithelialization and increased formation of granulation tissue.
Author Liu, Qingxian
Ni, Zhipeng
Yu, Haojie
Wang, Li
Lu, Hui
Huang, Yudi
Zhou, Haiying
AuthorAffiliation Department of Neurology and Endocrinology
Department of Orthopedics, the First Affiliated Hospital, College of Medicine
State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering
Zhejiang University
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Keywords prodrug
diabetic wound
anti-inflammation
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Snippet The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation...
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Title Multistage ROS-Responsive and Natural Polyphenol-Driven Prodrug Hydrogels for Diabetic Wound Healing
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