Abstract:Nonhealing diabetic wounds are common complications for diabetic patients. Because chronic hypoxia prominently delays wound healing, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. However, sustained oxygenation cannot be achieved by current clinical approaches, including hyperbaric oxygen therapy. Here, we present a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)–scavenging hydrogel. The hydrogel captures … Show more
“…Diabetes mellitus (DM) affects approximately 422 million patients worldwide [ 1 ]. About 25% of diabetic patients will eventually develop a diabetic foot ulcer (DFU) [ 1 , 2 ]. DFU, which ultimately leads to limb loss, disability, and even death, has caused serious medical, economic, and social burdens worldwide [ 3 ].…”
The extracellular matrix (ECM), comprising of hundreds of proteins, mainly collagen, provides physical, mechanical support for various cells and guides cell behavior as an interactive scaffold. However, deposition of ECM, especially collagen content, is seriously impaired in diabetic wounds, which cause inferior mechanical properties of the wound and further delay chronic wound healing. Thus, it is critical to develop ECM/collagen alternatives to remodel the mechanical properties of diabetic wounds and thus accelerate diabetic wound healing. Here, we firstly prepared mechanic-driven biodegradable PGA/SF nanofibrous scaffolds containing DFO for diabetic wound healing. In our study, the results in vitro showed that the PGA/SF-DFO scaffolds had porous three-dimensional nanofibrous structures, excellent mechanical properties, biodegradability, and biocompatibility, which would provide beneficial microenvironments for cell adhesion, growth, and migration as an ECM/collagen alternative. Furthermore, the data in vivo showed PGA/SF-DFO scaffolds can adhere well to the wound and have excellent biodegradability, which is helpful to avoid secondary damage by omitting the removal process of scaffolds. The finite element analysis results showed that the application of silk fibroin-based scaffolds could significantly reduce the maximum stress around the wound. Besides, PGA/SF-DFO scaffolds induced collagen deposition, re-vascularization, recovered impaired mechanical properties up to about 70%, and ultimately accelerated diabetic wound healing within 14 days. Thus, our work provides a promising therapeutic strategy for clinically chronic wound healing.
“…Diabetes mellitus (DM) affects approximately 422 million patients worldwide [ 1 ]. About 25% of diabetic patients will eventually develop a diabetic foot ulcer (DFU) [ 1 , 2 ]. DFU, which ultimately leads to limb loss, disability, and even death, has caused serious medical, economic, and social burdens worldwide [ 3 ].…”
The extracellular matrix (ECM), comprising of hundreds of proteins, mainly collagen, provides physical, mechanical support for various cells and guides cell behavior as an interactive scaffold. However, deposition of ECM, especially collagen content, is seriously impaired in diabetic wounds, which cause inferior mechanical properties of the wound and further delay chronic wound healing. Thus, it is critical to develop ECM/collagen alternatives to remodel the mechanical properties of diabetic wounds and thus accelerate diabetic wound healing. Here, we firstly prepared mechanic-driven biodegradable PGA/SF nanofibrous scaffolds containing DFO for diabetic wound healing. In our study, the results in vitro showed that the PGA/SF-DFO scaffolds had porous three-dimensional nanofibrous structures, excellent mechanical properties, biodegradability, and biocompatibility, which would provide beneficial microenvironments for cell adhesion, growth, and migration as an ECM/collagen alternative. Furthermore, the data in vivo showed PGA/SF-DFO scaffolds can adhere well to the wound and have excellent biodegradability, which is helpful to avoid secondary damage by omitting the removal process of scaffolds. The finite element analysis results showed that the application of silk fibroin-based scaffolds could significantly reduce the maximum stress around the wound. Besides, PGA/SF-DFO scaffolds induced collagen deposition, re-vascularization, recovered impaired mechanical properties up to about 70%, and ultimately accelerated diabetic wound healing within 14 days. Thus, our work provides a promising therapeutic strategy for clinically chronic wound healing.
“…Upon oxidization of 4-(hydroxymethyl)-phenylboronic acid pinacol ester in the AHPPE component by ROS, the component becomes acrylic acid component and releases soluble boronic acid. We have demonstrated in the previous study that AHPPE-containing polymers were able to effectively scavenge superoxide, hydroxyl radical, and H 2 O 2 [ 38 ]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…The wound images were taken at each time point. The wound size was calculated using ImageJ [ 38 ], and normalized to that on day 0.…”
Section: Methodsmentioning
confidence: 99%
“…ROS-sensitive hydrogel was synthesized by free radical polymerization of NIPAAm, HEMA and acrylated HPPE (AHPPE) using BPO as an initiator [ 38 , 42 , 43 ]. The molar feed ratio was 79/15/6 (abbreviated as ROSS-A6).…”
“…Consequently, controlling ROS and oxidative stress level in the diabetic wound is an important strategy to promote wound healing. Guan et al synthesized a material that could scavenge ROS from diabetic wounds, which promoted diabetic wound healing [16]. Zhao et al prepared a ROS scavenging hydrogel to accelerate wound healing by reducing ROS levels [17].…”
Although some studies have shown that some static magnetic fields (SMFs) can promote wound healing in diabetic mice, it is not clear whether the other diabetes complications, such as liver disease and diabetic nephropathy, can also be alleviated. Here, we constructed two simple magnetic plates using neodymium permanent magnets to examine the comprehensive effects of moderate SMFs on genetically obese leptin receptor-deficient db/db diabetic mice. We found that although the blood glucose was not obviously reduced by these two SMF settings, both of the glycated serum protein (GSP) and malondialdehyde (MDA) levels were significantly decreased (Cohen’s d = 2.57–3.04). Moreover, the wound healing, liver lipid accumulation, and renal defects were all significantly improved by SMF treatment (Cohen’s d = 0.91–2.05). Wound tissue examination showed obvious nuclear factor erythroid 2-related factor 2 (NRF2) level decrease (Cohen’s d = 2.49–5.40) and Ki-67 level increase (Cohen’s d = 2.30–3.40), indicating decreased oxidative stress and increased cell proliferation. In vitro cellular studies with fibroblast NIH3T3 cells showed that SMFs could reduce high glucose-induced NRF2 nucleus translocation (Cohen’s d = 0.87–1.15) and cellular reactive oxygen species (ROS) elevation (Cohen’s d = 0.92), indicating decreased oxidative stress. Consequently, high glucose-induced impairments in cell vitality, proliferation, and migration were all improved by SMF treatment. Therefore, our results demonstrate that these simple SMF devices could effectively reduce oxidative stress in diabetic mice and may provide a cost-effective physical therapy strategy to alleviate multiple diabetic complications in the future.
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