Three-dimensional cell-laden collagen scaffolds: From biochemistry to bone bioengineering

The bones can be viewed as both an organ and a material. As an organ, the bones give structure to the body, facilitate skeletal movement, and provide protection to internal organs. As a material, the bones consist of a hybrid organic/inorganic three-dimensional (3D) matrix, composed mainly of collagen, noncollagenous proteins, and a calcium phosphate mineral phase, which is formed and regulated by the orchestrated action of a complex array of cells including chondrocytes, osteoblasts, osteocytes, and osteoclasts. The interactions between cells, proteins, and minerals are essential for the bone functions under physiological loading conditions, trauma, and fractures. The organization of the bone's organic and inorganic phases stands out for its mechanical and biological properties and has inspired materials research. The objective of this review is to fill the gaps between the physical and biological characteristics that must be achieved to fabricate scaffolds for bone tissue engineering with enhanced performance. We describe the organization of bone tissue highlighting the characteristics that have inspired the development of 3D cell-laden collagenous scaffolds aimed at replicating the mechanical and biological properties of bone after implantation. The role of noncollagenous macromolecules in the organization of the collagenous matrix and mineralization ability of entrapped cells has also been reviewed. Understanding the modulation of cell activity by the extracellular matrix will ultimately help to improve the biological performance of 3D cell-laden collagenous scaffolds used for bone regeneration and repair as well as for in vitro studies aimed at unravelling physiological and pathological processes occurring in the bone.