DNA-Based Hydrogels with Multidrug Sequential Release for Promoting Diabetic Wound Regeneration.
Wei LiHui XieLiping GouYe ZhouHao WangRuoqing LiYong ZhangShuyun LiuJingping LiuYanrong LuZhengliang Eric HeNan ChenJiang LiYing ZhuChengshi WangMin LvPublished in: JACS Au (2023)
Diabetic wound (DW) regeneration is highly challenging due to persistent bacterial infection, excessive production of reactive oxygen species (ROS), prolonged inflammatory response, and insufficient angiogenesis. Ideal management requires the integration and sequential release of bactericidal, antioxidative, anti-inflammatory, and angiogenic agents during DW repair. Here, we develop a DNA-based multidrug hydrogel, termed Agilegel, to promote the efficient healing of DW. Hierarchically structured Agilegel can precisely control the sequential release of vascular endothelial growth factor-alpha (VEGF- α ), silver nanoclusters (AgNCs), and interleukin-10 (IL-10) through covalent bonds in its primary structure (phosphate backbone), noncovalent bonds in its secondary structure (base pairs), and physical encapsulation in its advanced structure (pores), respectively. We demonstrate that Agilegel can effectively eliminate bacterial infection through AgNCs and mitigate ROS production through DNA scaffolds. Moreover, during the inflammatory phase, Agilegel promotes the polarization of macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype using IL-10. Subsequently, Agilegel stimulates cell proliferation, angiogenesis, and extracellular matrix formation through the action of VEGF- α , thereby accelerating the closure of DW. Our results indicate that DNA hydrogels confer the capacity to regulate the sequential release of drugs, enabling them to effectively manage the phased intervention of multiple drugs in the treatment of complex diseases within physiological environments.
Keyphrases
- wound healing
- vascular endothelial growth factor
- extracellular matrix
- anti inflammatory
- reactive oxygen species
- circulating tumor
- endothelial cells
- inflammatory response
- cell proliferation
- cell free
- single molecule
- drug delivery
- tissue engineering
- stem cells
- cell death
- randomized controlled trial
- dna damage
- drug resistant
- type diabetes
- hyaluronic acid
- oxidative stress
- gold nanoparticles
- physical activity
- mental health
- nucleic acid
- circulating tumor cells
- sensitive detection
- drug release
- signaling pathway
- immune response
- drug induced
- weight gain
- multidrug resistant