Microneedle Patch Developed for Enhanced Diabetic Wound Treatment

Researchers from Nanjing Drum Tower Hospital, Southeast University, and Wenzhou Medical University have developed a microneedle patch for enhanced diabetic wound treatment. The innovative patch integrates MXene hydrogel with nitric oxide (NO) and hypoxia-inducible factor-1α (HIF-1α) plasmid. Published in the journal Engineering, this study directly addresses the persistent challenge of chronic and non-healing wounds prevalent among individuals with diabetes.

The Challenge of Diabetic Wounds

Diabetic wounds represent a significant healthcare burden, characterized by prolonged healing times and frequent complications. These wounds often suffer from chronic inflammation and impaired angiogenesis, which is the formation of new blood vessels. Current treatment options have limitations in skin penetration and typically focus on symptomatic relief rather than targeting the underlying biological mechanisms.

This new strategy offers a promising advancement, utilizing MXene hydrogel microneedles (MNs) for the precise and controllable delivery of NO and HIF-1α plasmid nanoparticles.

Microneedle Patch Mechanism

The newly developed microneedles are engineered from a biocompatible MXene gelatin hydrogel. This hydrogel incorporates gelatin coupled with tert-butyl nitrite (Gel-SNO) polymers. This unique design allows for the generation and release of nitric oxide (NO) when exposed to near-infrared (NIR) light.

The MXene additive within the patch is crucial for its functionality, exhibiting efficient photothermal conversion. Upon NIR exposure, this property causes the patch to dissolve, facilitating the release of HIF-1α plasmid nanoparticles directly into the dermis. The dual action of the patch ensures that the released NO actively reduces inflammation, while the HIF-1α plasmid stimulates essential neovascularization, promoting the formation of new blood vessels.

The patch’s integrated design allows for precise delivery, with NO tackling inflammation and the HIF-1α plasmid boosting new blood vessel formation.

Experimental Findings

In vitro experiments demonstrated the potent anti-inflammatory capabilities of NO released from Gel-SNO. It effectively reduced levels of pro-inflammatory cytokines such as IL-6 and TNF-α. Furthermore, HIF-1α plasmid nanoparticles successfully increased HIF-1α levels within the wounds, leading to enhanced vascular endothelial growth factor (VEGF) secretion and improved tissue regeneration.

In vivo studies conducted on diabetic mice showcased the remarkable efficacy of the MNs. The microneedles significantly accelerated wound closure, achieving an impressive 98% closure rate by day 10. Wounds treated with the MNs exhibited reduced inflammation, increased angiogenesis, and enhanced re-epithelialization. All animal procedures were rigorously authorized by the Animal Care and Use Committee of Nanjing Drum Tower Hospital.

Pathological evaluations provided further evidence of the MNs' positive impact. They promoted the formation of healthy granulation tissues and robust epithelial layers. Wounds treated with MNs also displayed denser collagen deposition, indicating improved extracellular matrix reconstruction and more effective tissue remodeling. Immunohistochemistry staining reinforced these findings, revealing lower IL-6 levels and higher VEGFA and CD31 levels in MN-treated wounds, confirming both reduced inflammation and enhanced angiogenesis.

Conclusion and Future Outlook

These compelling findings underscore the significant potential of MXene hydrogel microneedles in advanced wound healing and various other biomedical applications. The MNs' demonstrated ability to promote wound closure, mitigate inflammation, and foster tissue regeneration positions them as a strong candidate for the treatment of diabetic and other chronic wounds.

Further research is already planned to optimize the patch's design and mechanism, paving the way for eventual clinical application.

Study Reference:
Ding, W., et al. (2025). MXene Hydrogel Microneedles with Nitric Oxide and HIF-1α Plasmid Controllable Releasing for Wound Healing. Engineering. DOI: 10.1016/j.eng.2025.06.034.