A model for human calcium pyrophosphate crystal deposition disease: crystallization kinetics in a gelatin matrix

A model for the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in cartilage observed in human CPPD crystal deposition disease has been developed using diffusion of calcium and pyrophosphate ions through a denatured collagen matrix environment at physiologic pH. This model system uses biological grade gelatin and has allowed for the study of crystal deposition over a wide range of calcium and pyrophosphate concentrations, including physiologic levels. The model has reproducibly formed the two crystallographic dimorphs observed clinically: triclinic and monoclinic calcium pyrophosphate dihydrate. In addition, amorphous calcium pyrophosphate has been identified, and is the first species to form in the crystallization process and transforms to orthorhombic calcium pyrophosphate tetrahydrate. This in turn dissolves with a very localized increase in available pyrophosphate leading to the formation of triclinic and monoclinic calcium pyrophosphate dihydrate. The denatured collagen matrix has allowed for the formation of the two in vivo crystals at pyrophosphate concentrations lower than previously reported in solution studies.