Effects of Polyacrylic Acid with Different Molecular Weights on Stress Generation through Regulating the Growth of Calcium Carbonate within Collagen

Mineralized collagen fibrils are the building blocks of bone, and the mineralization of collagen fibrils is generally regulated by noncollagenous proteins (NCPs). However, the functions of NCPs are difficult to investigate in vivo. Here, we use poly(acrylic acid) (PAA) with different molecular weights (5, 50, 450, and 4000 kDa) as analogs of NCPs and explore their effects on collagen mineralization in vitro. All the PAA molecules can promote the intrafibrillar mineralization of calcium carbonate (CaCO₃) following these steps: the precursors infiltrate the gap zones of collagen, and transform into organized calcite nanocrystals within collagen. An increase in molecular weight significantly accelerates the mineralization rate of collagen films, approximately 0.67 μm min^-1 at 4000 kDa, four times that of 5 kDa (0.16 μm min^-1). However, the generation of contractile stress via intrafibrillar mineralization in tendons exhibits a contrary tendency. It reaches 24.2 MPa at 5 kDa, much higher than that of 4000 kDa (8.3 MPa), due to rapid mineralization causing severe extrafibrillar precipitation around the tendon. The controllable mineralization of collagen matrices may inspire the development of bone repair and regeneration in the future.