Mineralized DNA-collagen complex-based biomaterials for bone tissue engineering.

DNA is a highly polyanionic biomolecule that complexes with both collagen and hydroxyapatite. By combining these complexes, we synthesized nucleic-acid collagen complexes (NACC) mineralized with hydroxyapatite. The composite complexes were made using a short, monodisperse single-stranded DNA, type I collagen, and mineralizing medium. They rapidly self-assembled into both mineralized NACC microfibers and 3D NACC gels. At the nanoscale, these complexes are hierarchical, interwoven, curly nanofibrils resembling native extracellular matrix, which mineralized an interpenetrating nanocrystalline hydroxyapatite phase. Mineralization was able to be done either before or after NACC formation enabling temporal control of the process. In response to the NACC material, primary human osteoblasts took on an osteocyte-like morphology. Moreover, the cells agglomerated and remodeled the NACC gels into densified, tissue-like structures within 3 days. NACC fibers and gels have promise not only as osteoconductive coatings and scaffolds, but as coatings and scaffolds for any tissue using this new form of naturally-derived biomaterials.