Emerging cell-free DNA scavenging biomaterials for inflammatory diseases: From mechanisms to therapies

Cell free deoxyribonucleic acids (cfDNA), fragments of DNA released by cell death or active secretion, has emerged as an inflammatory mediator closely associated with many inflammatory diseases. cfDNA-scavenging biomaterials could effectively capture or degrade cfDNA in body fluids, avoiding the activation of cellular innate and adaptive immune responses and thus inhibiting the development of inflammatory process. The development of cfDNA-scavenging biomaterials is in its infancy yet fast-growing. In this review, after a brief introduction of the dynamic balance of cfDNA production and clearance under physiological conditions, we outline three pro-inflammatory signaling pathways of cfDNA and identify the relationship between these signaling pathways and various inflammatory diseases. Then, we systematically summarize the category, scavenging mechanisms, and anti-inflammatory applications of existing cfDNA-scavenging biomaterials. We also propose the basic design principles of cfDNA-scavenging biomaterials for potential clinical translation. Finally, we provide personal perspectives on remaining challenges and future opportunities of cfDNA-scavenging biomaterials for anti-inflammation. STATEMENT OF SIGNIFICANCE: cfDNA (cell free deoxynucleic acids) has emerged as an important inflammatory mediator closely associated with many inflammatory diseases. In this review, we first introduce the dynamic balance of cfDNA production and clearance under physiological conditions. Then, we outline three pro-inflammatory signaling pathways of cfDNA and identify the relationship between these signaling pathways and various inflammatory diseases. Next, we systematically summarize the category, scavenging mechanisms, and anti-inflammatory applications of existing cfDNA-scavenging biomaterials. Finally, we provide personal perspectives on remaining challenges and future opportunities of cfDNA-scavenging biomaterials for anti-inflammation. This review provides a comprehensive overview of cfDNA-scavenging biomaterials for researchers and clinicians, facilitating the development of novel anti-inflammatory agents for inflammatory diseases.