BLT Regent Supports Diabetic Wound Healing: Sustained-Release Ulcer-Protective Microarray Patch With Dihydrocapsaicin for Diabetic Wound Regeneration

New progress has been made in diabetic wound regeneration therapy using sustained-release dihydrocapsaicin-loaded microneedle patches.

Professor Yihe Hu and Professor Xianzhu Zhang from the Department of Orthopedics, The First Affiliated Hospital of Zhejiang University School of Medicine, in collaboration with Professor Zonghan Xu from the Department of Orthopedics, Suzhou Municipal Hospital, published their findings in “ Exploration” (IF = 22.5, Q1 journal).

This study provides a new integrated transdermal therapeutic strategy for diabetic foot ulcer repair by constructing a multifunctional microneedle patch system that enables long-term dihydrocapsaicin delivery, antioxidant regulation, inflammation modulation, and vascular regeneration.

The global diabetic population has reached nearly 529 million, and diabetic foot ulcers (DFUs), as a severe and common complication of diabetes, can lead to persistent pain, impaired wound healing, amputation, and even death. Current clinical treatments face significant limitations, including antibiotic resistance, lack of biological activity in conventional dressings, and short half-lives of growth factors, making it difficult to simultaneously address excessive oxidative stress and impaired angiogenesis in diabetic wounds.

To overcome these challenges, this study developed a gelatin methacrylate (GelMA) hydrogel-based cerium metal-organic framework (Ce-MOF) microneedle delivery system, MN-MOF@DHC. Dihydrocapsaicin (DHC), which exhibits antioxidant, anti-inflammatory, and pro-angiogenic activities, was encapsulated into Ce-UiO-66-CH₃ nanoparticles and incorporated into a transdermal microneedle patch. By leveraging the enzyme-like catalytic activity and porous drug-loading structure of Ce-MOF, the system achieved sustained DHC release for up to 28 days. Through synergistic regulation of reactive oxygen species (ROS) clearance, macrophage M1/M2 polarization, and endothelial angiogenesis, MN-MOF@DHC simultaneously improved inflammation, oxidative damage, and vascular regeneration defects, providing an integrated multifunctional transdermal therapeutic strategy for comprehensive diabetic foot ulcer repair.

The study successfully developed the MN-MOF@DHC composite microneedle patch. The Ce-MOF nanocarrier demonstrated three types of antioxidant enzyme-like activities, while the composite microneedle exhibited excellent mechanical properties, swelling behavior, and transdermal performance, enabling long-term DHC release for up to 28 days with high biosafety. In vitro experiments showed that the system synergistically eliminated cellular and mitochondrial ROS, inhibited endothelial cell apoptosis, promoted macrophage polarization from pro-inflammatory M1 phenotype toward reparative M2 phenotype, and significantly enhanced endothelial cell migration and angiogenesis. The bidirectional synergy between Ce-MOF and DHC further amplified the tissue repair effects.

Both diabetic dorsal wound models and diabetic foot ulcer models in rats demonstrated that MN-MOF@DHC significantly accelerated wound closure, reduced tissue defects, and promoted organized collagen deposition. Meanwhile, the system effectively decreased oxidative stress levels, alleviated chronic inflammation, and inhibited tissue cell apoptosis. By activating the VEGF/Ang-1 signaling pathway, MN-MOF@DHC increased the density of newly formed and mature blood vessels, addressing the three major pathological challenges of diabetic foot ulcers: oxidative imbalance, persistent inflammation, and impaired vascular regeneration. This strategy provides a safe, efficient, and translationally promising approach for minimally invasive and integrated diabetic wound treatment.

Experiments using BLT Regent

In this study, Guangzhou Biolight Biotechnology’ s CCK-8 Kit was used to evaluate HUVEC cell viability. Cells from the control group, DHC group, MN-MOF group, and MN-MOF@DHC group were seeded into 24-well plates and cultured at 37℃ with 5% CO₂ under saturated humidity conditions. After 24 h of drug treatment, cell viability was measured. The results showed that on days 1, 3, and 5, no significant differences in cell viability were observed among the DHC, MN-MOF, and MN-MOF@DHC groups compared with the control group, confirming the excellent biocompatibility of MN-MOF@DHC and its suitability for wound repair applications.

DOI: org/10.1002/EXP.20250129