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Published on: August 21, 2021
Multifunctional Polyphenol-Polymer Nanocomposite Hydrogel Targeting Inflammation, Oxidative Stress, and Infection in
Yuefei Zhu1,2, Na Yan1, Yongqiang Xiao1,3
1Department of Biomedical Engineering, Columbia University, New York, New York, USA.
Abstract:
Chronic diabetic wounds are characterized by prolonged inflammation, elevated reactive oxygen species (ROS), impaired angiogenesis, and delayed healing, often leading to tissue necrosis and amputation. Conventional wound dressings rarely address oxidative stress, dysregulated inflammation, bacterial infection, and local hyperglycemia simultaneously. Here, we developed a multifunctional nanoplatform consisting of tannic acid (TA)-complexed chitosan-polyethylenimine-phenylboronic acid (CPB-TA) nanoparticles embedded within a thermoresponsive poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAm-co-AAc)] hydrogel. CPB-TA nanoparticles exhibit dual cfDNA-scavenging and antioxidant activity, sequestering cfDNA through combined cationic binding and polyphenol interactions, and reducing ROS via complementary antioxidant mechanisms, thereby dampening inflammatory signaling and protecting reparative cells. The phenylboronic acid groups reversibly capture glucose through dynamic boronate ester bonds, helping to alleviate local hyperglycemia. The hydrogel matrix is designed to be responsive to body temperature, promoting localized delivery of CPB-TA at the wound site. In vitro, CPB-TA nanoparticles promoted macrophage polarization from M1 to M2, protected endothelial cells from oxidative damage, and exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. In vivo, topical application of CPB-TA@hydrogel accelerated wound closure, enhanced re-epithelialization, and increased collagen deposition in non-infected and S. aureus-infected diabetic mouse models. This multifunctional, mechanism-targeted strategy provides a rational, disease-relevant approach for treating chronic diabetic wounds.
Insights
A new nanoplatform with tannic acid (TA)-complexed nanoparticles in a thermoresponsive hydrogel effectively treats chronic diabetic wounds by reducing inflammation, oxidative stress, and hyperglycemia, accelerating healing.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Wound Healing Research
Background:
- Chronic diabetic wounds suffer from persistent inflammation, oxidative stress, and hyperglycemia, hindering healing.
- Current treatments often fail to address these multiple pathological factors simultaneously.
- This necessitates innovative therapeutic strategies for effective diabetic wound management.
Purpose of the Study:
- To develop a multifunctional nanoplatform for simultaneous treatment of key pathological factors in diabetic wounds.
- To create tannic acid (TA)-complexed chitosan-polyethylenimine-phenylboronic acid (CPB-TA) nanoparticles within a thermoresponsive hydrogel.
- To evaluate the therapeutic efficacy of this nanoplatform in preclinical models of diabetic wounds.
Main Methods:
- Fabrication of CPB-TA nanoparticles and their incorporation into a thermoresponsive P(NIPAm-co-AAc) hydrogel.
- In vitro assessment of nanoparticle functionalities including cfDNA scavenging, antioxidant activity, glucose regulation, and cellular effects (macrophage polarization, endothelial cell protection, antibacterial activity).
- In vivo evaluation of the CPB-TA@hydrogel in non-infected and Staphylococcus aureus-infected diabetic mouse models for wound closure, re-epithelialization, and collagen deposition.
Main Results:
- CPB-TA nanoparticles demonstrated dual cfDNA-scavenging and antioxidant properties, reducing inflammation and oxidative stress.
- The phenylboronic acid component effectively alleviated local hyperglycemia via reversible glucose capture.
- In vitro studies showed enhanced macrophage M2 polarization, endothelial cell protection, and antibacterial effects.
- In vivo application significantly accelerated wound healing, improved tissue regeneration, and increased collagen deposition in diabetic wound models.
Conclusions:
- The developed multifunctional nanoplatform offers a promising, mechanism-targeted approach for treating chronic diabetic wounds.
- Simultaneous targeting of inflammation, oxidative stress, hyperglycemia, and bacterial infection contributes to enhanced wound healing.
- This strategy represents a significant advancement in the development of advanced wound care technologies for complex wounds.
