DNA as a promising biomaterial for bone regeneration and potential mechanisms of action

DNA nanotechnology has created new possibilities for the use of DNA in tissue regeneration - an important advance for DNA use beyond its paradigmatic role as the hereditary biomacromolecule. Biomaterials containing synthetic or natural DNA have been proposed for several applications including drug and gene delivery, and more recently, as osteoconductive biomaterials. This review provides an in-depth discussion of studies that have used DNA-based materials for biomineralization and/or bone repair, with expansion on the topic of DNA hydrogels specifically, and the advantages they offer for advancing the field of bone regeneration. Four mechanisms of action for the osteoconductive capabilities of DNA-based materials are discussed, and a proposed model for degradation of these materials and its link to their osteoconductive properties is later presented. Finally, the review considers current limitations of DNA-based materials and summarizes important aspects that need to be addressed for future application of DNA nanotechnology in tissue repair. STATEMENT OF SIGNIFICANCE: Herein we summarize the developing field of DNA-based materials for biomineralization and bone repair, with a focus on DNA hydrogels. We first provide a comprehensive review of different forms of DNA-based materials described thus far which have been shown to enhance bone repair and mineralization (namely DNA coatings, DNA-containing pastes, DNA nanostructures and DNA hydrogels). Next, we describe four different mechanisms by which DNA-based materials could be exerting their osteogenic effect. Then, we propose a novel model that links DNA degradation and osteoconductivity. Lastly, we suggest possible research directions to enhance DNA-based materials for future clinical application. The suggested mechanisms and the proposed model can guide future research to better understand how DNA functions as a mineral- and bone-promoting molecule.