A Nanozyme‐Immobilized Hydrogel with Endogenous ROS‐Scavenging and Oxygen Generation Abilities for Significantly Promoting Oxidative Diabetic Wound Healing

Abstract

Non-healing wound is a common complication of diabetic patients associated with high morbidity and mortality. Engineered therapeutic hydrogels have enviable advantages in tissue regeneration, however, they are suboptimal for the healing of diabetic wounds characterized by reactive oxygen species (ROS) accumulation and chronic hypoxia. Here, a unique biological metabolism-inspired hydrogel, for ameliorating this hostile diabetic microenvironment, is presented. Consisting of natural polymers (hydrazide modified hyaluronic acid and aldehyde modified hyaluronic acid) and a metal-organic frameworks derived catalase-mimic nanozyme (𝝐-polylysine coated mesoporous manganese cobalt oxide), the engineered nanozyme-reinforced hydrogels can not only capture the endogenous elevated ROS in diabetic wounds, but also synergistically produce oxygen through the ROS-driven oxygen production ability. These fascinating properties of hydrogels protect skin cells (e.g., keratinocytes, fibroblasts, and vascular endothelial cells) from ROS and hypoxia-mediated death and proliferation inhibition. Diabetic wounds treated with the nanozyme-reinforced hydrogels highlight the potential of inducing the macrophages polarization from pro-inflammatory phenotype (M1) to anti-inflammatory subtype (M2). The hydrogel dressings demonstrate a prominently accelerated healing rate as shown by alleviating the excessive inflammatory, inducing efficiently proliferation, re-epithelialization, collagen deposition, and neovascularization. This work provides an effective strategy based on nanozyme-reinforced hydrogel as a ROS-driven oxygenerator for enhancing diabetic wound healing.

Thermosensitive hydrogel loaded with concentrated growth factors promote bone repair in segmental bone defects

“…In recent years, diverse drug delivery systems have been developed for biomedical applications ( Zhang et al, 2022a ; Gao et al, 2022 ). Hydrogels have been widely used in biomedical fields because of their bionic three-dimensional (3D) network structure and loaded bioactive substances as drug delivery systems ( Liu et al, 2018 ; Li et al, 2021b ; Li et al, 2022c ). Poloxamer 407 is a thermosensitive material with diversified capabilities, such as reversible thermo-sensitive property, drug encapsulation and sustained delivery ability, superior bioavailability, biocompatibility, and so on, which is considered to be an alternative injectable drug sustained-release system for enhancing bone regeneration and repair ( Bai et al, 2020a ; Chen et al, 2021 ).…”

“…CGFs is the third-generation platelet concentrate extracted and isolated from blood, which contains a large quantity and variety of growth factors, including PDGF, TGF-β1, TGF-β2, FGF, VEGF, IGF, and so on, and have been applied in clinical practice to promote Frontiers in Bioengineering and Biotechnology frontiersin.org tissue repair (Lokwani et al, 2020;Li et al, 2021a). CGFs, which does not contain bovine thrombin and anticoagulants, overcome the disadvantages in preparation and the high cost of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), as well as release various growth factors that promote cell proliferation and differentiation.…”

“…CGFs, which does not contain bovine thrombin and anticoagulants, overcome the disadvantages in preparation and the high cost of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), as well as release various growth factors that promote cell proliferation and differentiation. Therefore, CGFs are regarded as ideal biological materials, which can partially address the limitations of traditional treatment strategies in critical-size bone defects regeneration (Li et al, 2021a). Previous studies have indicated that the combination of CGFs and bone substitute materials can significantly induce bone repair (Xu et al, 2019;Fang et al, 2020).…”

“…Platelets are a natural source of multiple growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and insulin-like growth factor (IGF), transforming growth factor β1 (TGF-β1), TGF-β2, and so on, which play an important role in promoting cell proliferation, differentiation, tissue regeneration and repair (Intini, 2009). Concentrated growth factor (CGFs) is a thirdgeneration platelet concentrate extracted from blood, which was developed by Sacco in the year 2006 (Lokwani et al, 2020;Li et al, 2021a). Previous study reported that CGFs contains more abundant growth factors than the other platelet-based products, e.g., platelet-rich plasma (PRP) or platelet-rich fibrin (PRF) (Qiao et al, 2017).…”

Naturally derived injectable hydrogels with ROS-scavenging property to protect transplanted stem cell bioactivity for osteoarthritic cartilage repair

“…The H 2 O 2 depletion ability of the HA-EGCG hydrogel was monitored by mixing H 2 O 2 (1 mM, 1 ml) and hydrogel (1 ml) in PBS at 37 °C as described previously ( Li et al, 2022a ). After designated times, the supernatant (100 µL) was collected and added 200 µL of Ti(SO 4 ) 2 solution.…”