The nanostructure of bone has been replicated using a polymer-induced liquid-precursor (PILP) mineralization process. This polymer-mediated crystallization process yields intrafibrillar mineralization of collagen with uniaxially-oriented hydroxyapatite crystals. The process-directing agent, an anionic polymer which we propose mimics the acidic non-collagenous proteins associated with bone formation, sequesters calcium and phosphate ions to form amorphous precursor droplets that can infiltrate the interstices of collagen fibrils. In search of a polymeric agent that produces the highest mineral content in the shortest time, we have studied the influence of various acidic polymers on the in vitro mineralization of collagen scaffolds via the PILP process. Among the polymers investigated were poly-L aspartic acid (PASP), poly-L-glutamic acid (PGLU), polyvinylphosphonic acid (PVPA), and polyacrylic acid (PAA). Our data indicate that PASP and the combination of PGLU/PASP formed stable mineralization solutions, and yielded nano-structured composites with the highest mineral content. Such studies contribute to our goal of preparing biomimetic bone graft substitutes with composition and structure that mimic bone.