Thermosensitive Hydrogel Incorporating Prussian Blue Nanoparticles Promotes Diabetic Wound Healing via ROS Scavenging and Mitochondrial Function Restoration

Abstract

Diabetic foot ulcer is a serious complication in diabetes patients, imposing a serious physical and economic burden to patients and to the healthcare system as a whole. Oxidative stress is thought to be a key driver of the pathogenesis of such ulcers. However, no antioxidant drugs have received clinical approval to date, underscoring the need for the further development of such medications. Hydrogels can be applied directly to the wound site, wherein they function to prevent infection and maintain local moisture concentrations, in addition to serving as a reservoir for the delivery of a range of therapeutic compounds with the potential to expedite wound healing in a synergistic manner. Herein, we synthesized Prussian blue nanoparticles (PBNPs) capable of efficiently scavenging reactive oxygen species (ROS) owing to their ability to mimic the activity of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD). In the context of in vitro oxidative stress, these PBNPs were able to protect against cytotoxicity, protect mitochondria from oxidative stress-related damage, and restore nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activity. To expand on these results in an in vivo context, we prepared a thermosensitive poly (d,L-lactide)-poly(ethylene glycol)-poly(d,L-lactide) (PDLLA-PEG-PDLLA) hydrogel (PLEL)-based wound dressing in which PBNPs had been homogenously incorporated, and we then used this dressing as a platform for controlled PBNP release. The resultant PBNPs@PLEL wound dressing was able to improve diabetic wound healing, decrease ROS production, promote angiogenesis, and reduce pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels within diabetic wounds. Overall, our results suggest that this PBNPs@PLEL platform holds great promise as a treatment for diabetic foot ulcers.

Preparation, Characterization and Multiple Biological Properties of Peptide-Modified Cerium Oxide Nanoparticles

“…Superoxide dismutase (SOD) is a critical antioxidant enzyme in cells; it can catalyze the decomposition of O 2 − into O 2 and H 2 O 2 [ 50 ]. The SOD mimetic activity of the CeO 2 @PAA@RGD was evaluated using the WST-8 method.…”

Metal-organic framework-based nanoplatform enhance fibroblast activity to treat periodontitis

“…Figure 4 showed that MPB had satisfied effect in promoting fibroblast proliferation. Previous reports have proved that PB nanoparticles could promote the activity of fibroblast cells and have a positive effect on collagen deposition during soft tissue healing 48,49) . Our results also suggested that MPB had satisfied effect in promoting fibroblast proliferation and migration (Figs.…”

Current Advances in the Development of Hydrogel-Based Wound Dressings for Diabetic Foot Ulcer Treatment

“…For this reason, a lot of research efforts are currently focusing on the development of materials with scavenging properties that can protect the wound bed from the mitochondrial damage inflicted by reactive oxygen species (ROS). In this sense, the recent work conducted by Xu et al involved the fabrication of a poly(d,L-lactide)-PEG-poly(d,L-lactide) (PLGA-PEG-PLGA) hydrogel for the encapsulation and controlled release of Prusian blue nanoparticles (PBNPs), a synthetic material that can mimic the ROS scavenging activity of naturally occurring antioxidant enzymes, such as peroxidase, catalase, and superoxide dismutase [ 72 ]. The thermosensitive properties of the prepared hydrogel allowed in situ gelation at physiological temperature.…”