From biomarkers to therapeutic targets: Biomaterial-mediated cfDNA scavenging in inflammation

Authors

• Shibo Liu, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
• Xu Cheng, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
• Linyi Liu, MaineHealth Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME, USA.
• En Luo, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
• Dan Shao, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
• Hanyao Huang, Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
• Hanghang Liu, MaineHealth Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME, USA.

Document Type

Article

Publication Date

10-13-2026

Institution/Department

Center for Molecular Medicine

Journal Title

Biomaterials

Abstract

Cell-free DNA (cfDNA) displays disease-dependent changes in abundance, fragmentation, composition, and tissue origin. Beyond serving as a noninvasive biomarker, persistent cfDNA can act as a damage-associated molecular pattern, activating TLR9, cGAS-STING, inflammasome signaling, and thromboinflammation. This review synthesizes advances in cfDNA biology, clinical applications, and therapeutic scavenging across inflammatory diseases. We critically evaluate the extent to which current clinical studies support diagnostic, prognostic, and causal conclusions while considering methodological heterogeneity. Particular emphasis is placed on how biomaterials transform cfDNA recognition into treatment. We trace the evolution from free nucleases and soluble cationic agents to nanostructured platforms that integrate DNA sequestration with retention, degradation, lesion targeting, or immunomodulation. Comparison of cationic polymers, dendrimers, core-shell nanoparticles, hydrogels, microneedles, nanosheets, and nuclease-enabled systems reveals how material architecture governs cfDNA accessibility, stability in biofluids, tissue distribution, and therapeutic efficacy. Localized and stimuli-responsive designs may improve selectivity and reduce systemic toxicity, but most efficacy evidence remains preclinical. Clinical translation therefore requires standardized cfDNA measurement, realistic biofluid testing, rigorous pharmacology, scalable manufacturing, and prospective demonstration that selective cfDNA removal improves outcomes without compromising host defense.

First Page

124700

Recommended Citation

Liu, Shibo; Cheng, Xu; Liu, Linyi; Luo, En; Shao, Dan; Huang, Hanyao; and Liu, Hanghang, "From biomarkers to therapeutic targets: Biomaterial-mediated cfDNA scavenging in inflammation" (2026). MaineHealth Maine Medical Center. 4710.
https://knowledgeconnection.mainehealth.org/mmc/4710