Modification of surfaces mimicking unique chemical and physical features of mineralized tissues is of major interest for obtaining biomaterials for replacing and regenerating biological tissues. Here, human salivary statherin-inspired genetically engineered recombinamers (ELRs, HSS) on biomedical surfaces regulates mineralization to form an amorphous-calcium-phosphate (ACP) layer that reproduces the original substrate nanotopography. The HSS-ELRs carry a statherin-derived peptide with high affinity to tooth enamel. They are tethered to nanorough surfaces and mineralized using an enzyme-directed process. A homogeneous layer of ACP-minerals forms on HSS-coated surfaces retaining the original nanotopography of the substrate. In contrast, biomineralization of control surfaces results in uncontrolled growth of minerals. This suggest the statherin-inspired ELRs have ability to induce and control growth of the minerals on the biofunctional surfaces. Likely, the HSS-ELR coating have similar bioactivity to that of statherin in human saliva. The hybrid nanorough surfaces improve adhesion and differentiation of preosteoblasts and show potential for dental and orthopedic implants integration. This method enables the combination and tailoring of nanotopographical and biochemical cues to design functionalized surfaces to investigate and potentially direct the stem cell fate.