Researchers from Nanjing Drum Tower Hospital, Southeast University, and Wenzhou Medical University have developed a novel microneedle patch that combines MXene hydrogel with nitric oxide (NO) and hypoxia-inducible factor-1α (HIF-1α) plasmid for enhanced diabetic wound treatment. This study, published in the journal Engineering, presents a promising approach to addressing the chronic and non-healing wounds often associated with diabetes.

Diabetic wounds are a significant healthcare challenge due to their prolonged healing times and the complications they can cause. These wounds are often characterized by excessive inflammation and impaired angiogenesis, which hampers the formation of new blood vessels and delays the healing process. Traditional treatments have limitations, such as difficulty in penetrating the skin barrier and primarily providing symptomatic relief rather than addressing the underlying pathological mechanisms. To overcome these challenges, the researchers proposed a new strategy using MXene hydrogel microneedles (MNs) that can deliver NO and HIF-1α plasmid nanoparticles in a controlled manner.

The microneedles are made from a biocompatible MXene gelatin hydrogel and incorporate gelatin coupled with tert-butyl nitrite (Gel-SNO) polymers. This design allows for the generation and release of NO under near-infrared (NIR) light irradiation due to the thermal effect. Simultaneously, the enhanced photothermal conversion efficiency of the MXene additive enables the microneedle patch to quickly dissolve and release the enclosed HIF-1α plasmid nanoparticles into the dermis when exposed to NIR radiation. The released NO effectively reduces inflammation, while the HIF-1α plasmid induces neovascularization, promoting wound healing.

In vitro experiments demonstrated that the NO released from Gel-SNO achieved potent anti-inflammatory activity, reducing the expression of pro-inflammatory cytokines such as IL-6 and TNF-α. Additionally, the HIF-1α plasmid nanoparticles enhanced the level of HIF-1α in wounds, triggering the secretion of vascular endothelial growth factor (VEGF) and improving tissue regeneration. In vivo studies using a diabetic mouse model showed that the MNs significantly accelerated wound closure, with a wound closure rate of 98% by day 10. The treated wounds exhibited reduced inflammation, increased angiogenesis, and enhanced re-epithelialization. [The experimental procedures were authorized by the Animal Care and Use Committee of the Nanjing Drum Tower Hospital, with approval number 2022AE01016 issued by the Laboratory Animal Welfare Ethics Committee of Nanjing Drum Tower Hospital.]

The study also evaluated the pathological features of the wounds. Histological analysis revealed that the MNs promoted the formation of healthy granulation tissues and epithelial layers, crucial components for effective wound healing. Furthermore, the wounds treated with the MNs showed more ordered and dense collagen deposition, indicating enhanced extracellular matrix reconstruction and tissue remodeling. Immunohistochemistry staining showed lower levels of IL-6 and higher levels of VEGFA and CD31 in wounds treated with the MNs, suggesting reduced inflammation and enhanced angiogenesis.

The findings of this study highlight the potential of MXene hydrogel microneedles in wound healing and other related biomedical fields. The ability of these MNs to promote wound closure, reduce inflammation, and enhance tissue regeneration makes them a promising candidate for treating diabetic wounds and potentially other types of chronic wounds. Future research may focus on further optimizing the MNs and exploring their applications in clinical settings to improve wound care and patient outcomes.

The paper “MXene Hydrogel Microneedles with Nitric Oxide and HIF-1α Plasmid Controllable Releasing for Wound Healing,” is authored by Wanchuan Ding, Xiangyi Wu, Yi Cheng, Ling Lu, Weijian Sun, Yuanjin Zhao. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.06.034. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.