Multistage ROS-Responsive and Natural Polyphenol-Driven Prodrug Hydrogels for Diabetic Wound Healing
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.
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Polyphenol-phenylboronic acid hydrogels formed through dynamic borate ester bonds respond to glucose and ROS and demonstrate wet adhesion and anti-inflammatory properties.
“Among these, polyphenol-phenylboronic acid (PBA) hydrogels, formed through dynamic borate ester bond, not only respond to Glu and ROS but also demonstrate wet adhesion and anti-inflammatory properties27,28.”
From Microenvironment-responsive multifunctional enzyme-linked hydrogel for diabetic bone defect regeneration. (2025) · cites this paper as [28]
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“Among these, polyphenol-phenylboronic acid (PBA) hydrogels, formed through dynamic borate ester bond, not only respond to Glu and ROS but also demonstratewetadhesionandanti-in fl ammatoryproperties 27,28 .”
- Authors
- Ni, Z., Yu, H., Wang, L., Huang, Y., Lu, H., Zhou, H., & Liu, Q.
- Affiliations
- State Key Laboratory of Chemical Engineering (CN)
- Department of Orthopedics, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou310003, Zhejiang Province, China
- First Affiliated Hospital Zhejiang University (CN)
- Jiaxing University (CN)
- Corresponding author
- Yu, Haojie
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-11-16
- Volume
- 14
- Issue
- 47
- Pages
- 52643-52658
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W4309119346
- Cited by
- 137
- References
- 41
- Citations by year
- 2026: 38 · 2025: 47 · 2024: 31 · 2023: 21
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (22275163)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Keywords
- diabetic wound healing, reactive oxygen species-responsive hydrogel, tannic acid, polyphosphazenes, polyvinyl alcohol, antioxidant hydrogel, antibacterial hydrogel, Escherichia coli, nanogels, cell migration, inflammatory cytokines, TGF-β1, collagen expression, re-epithelialization, streptozotocin-induced diabetes, wound dressings
- MeSH terms
- Animals, Anti-Bacterial Agents, Diabetes Mellitus, Escherichia coli, Prodrugs, Tannins, Wound Healing, Reactive Oxygen Species, Hydrogels, Rats, Polyphenols
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