Native and biomimetic DNA structures have been demonstrated to impact materials synthesis under a variety of conditions but have only just begun to be explored in this role compared to other biopolymers such as peptides, proteins, polysaccharides, and glycopolymers. One selected DNA aptamer has been explored in calcium phosphate and calcium carbonate mineralization, demonstrating sequence-dependent control of kinetics, morphology, and crystallinity. This aptamer is here applied to a biologically-relevant bone model system that uses collagen hydrogels. In the presence of the aptamer, intrafibrillar collagen mineralization is observed compared to negative controls and a positive control using well-studied poly-aspartic acid. The mechanism of interaction is explored through affinity measurements, kinetics of calcium uptake, and kinetics of aptamer uptake into the forming mineral. There is a marked difference observed between the selected aptamer containing a G-quadruplex secondary structure compared to a control sequence with no G-quadruplex. It is hypothesized that the equilibrium interaction of the aptamer with calcium-phosphate precursors and with the collagen itself leads to slow kinetic mineral formation and a morphology appropriate to bone. This points to new uses for DNA aptamers in biologically-relevant mineralization systems and the possibility of future biomedical applications. STATEMENT OF SIGNIFICANCE: Collagen is the protein structural component that mineralizes with calcium phosphate to form durable bone. Crystalline calcium phosphate must be infused throughout the collagen fiber structure to produce a strong material. This process is assisted by soluble proteins that interact with both calcium phosphate precursors and the collagen protein and has been proposed to follow a polymer-induce liquid precursor (PILP) model. Further understanding of this model and control of the process through synthetic, biomimetic molecules could have significant advantages in biomedical, restorative procedures. For the first time, synthetic DNA aptamers with specific secondary structures are here shown to influence and direct collagen mineralization. The mechanism of this process has been studied to demonstrate an important equilibrium between the DNA aptamer, calcium phosphate precursors, and collagen.