Capture and Storage of Cell‐free DNA via Bio‐informational Hydrogel Microspheres

Abstract Excessive cell‐free DNA (cfDNA) can induce chronic inflammation by activating intracellular nucleic acid sensors. Intervention in cfDNA‐mediated “pro‐inflammatory signaling transduction” could be a potential alleviating strategy for chronic inflammation, such as in diabetic wounds. However, effectively and specifically downgrading cfDNA concentration in the pathological microenvironment remains a challenge. Therefore, this work prepares free‐standing polydopamine nanosheets through DNA‐guided assembly and loaded them into microfluidic hydrogel microspheres. The π─π stacking/hydrogen bonding interactions between polydopamine nanosheets and the π‐rich bases of cfDNA, along with the cage‐like spatial confinement created by the hydrogel polymer network, achieved cfDNA capture and storage, respectively. Catechol in polydopamine nanosheets can also assist in reducing reactive oxygen species (ROS) levels. Efficient cfDNA binding independent of serum proteins, specific interdiction of abnormal activation of cfDNA‐associated toll‐like receptor 9, as well as down‐regulation of inflammatory cytokines and ROS levels are shown in this system. The chronic inflammation alleviating and the pro‐healing effects on the mice model with diabetic wounds are also investigated. This work presents a new strategy for capturing and storing cfDNA to intervene in cell signaling transduction. It also offers new insights into the regulatory mechanisms between inflammatory mediators and biomaterials in inflammation‐related diseases.