Collagen biomineralization: pathways, mechanisms, and thermodynamics

Over the past two decades, numerous studies have investigated and characterized the transient and amorphous phases in early stages of mineralization as well as their transition mechanisms to apatite crystals in buffered solutions. Recently more attention has been drawn to the identification and characterization of collagen structure and how it can affect mineralization in contact with non-collagenous protein and calcium phosphate clusters. This review highlights some of the pathways and mechanisms through which amorphous calcium phosphate clusters form. The conversion of these clusters into hydroxyapatite crystals is also reviewed. The thermodynamic aspects of nucleation and growth processes based on classical and non-classical nucleation theories related to hydroxyapatite are discussed. In addition, this paper is written to address the significant progress on mechanisms and pathways engaged in mineralization of collagen fibrils. Finally, it addresses some of the breakthroughs and limitations in the field of collagen biomineralization studies and new challenges in this field of study.