Journal
BIOMATERIALS
Volume 54, Issue -, Pages 106-115Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.03.013
Keywords
Gene therapy; Implant rejection; Intracellular DNA sensors; Vaccines; Cancer therapy
Funding
- National Institutes of Health [R21EB007494]
- National Science Foundation CAREER Award [0748285]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0748285] Funding Source: National Science Foundation
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Biominerals (or microcalcification) deposited in soft tissues are associated with a number of pathogeneses and cancer progressions. Biominerals have also shown promise for DNA delivery and tissue engineering. Biominerals themselves may stimulate NALP3 inflammasomes, and DNA delivered by biominerals can potentially engage with intracellular DNA sensors, resulting in unwanted inflammatory responses. In this study, a library of biominerals doped with or without DNA is formed through surface-induced biomineralization. It is demonstrated that empty biominerals stimulate NALP3 inflammasomes and induce the production of IL-1 beta. They are also able to activate mouse embryonic fibroblasts (MEFs) and induce inflammatory cytokines, i.e. IL-6. DNA delivered by biominerals escapes the detection of TLR9, but activates DAI and inflammasomes. Furthermore, it is shown that the level of both IL-1 beta and IL-6 is correlated with the composition of biominerals, in particular the ratio of Mg(Sr) to Ca, and the pH sensitivity of biominerals. These results provide insights into the design of safe and effective DNA delivery systems and biocompatible implants as well as the understanding of the pathogeneses of biominerals deposited in soft tissues. (C) 2015 Elsevier Ltd. All rights reserved.
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