Schematic representation of top-down approaches to generation of bioactive constructs for bone tissue engineering. In the natural route for the top-down approaches, a native bone can be decellularized and demineralized to obtain a natural matrix in various forms (e.g., powder, paste, putty, injectable; not shown) devoid of cells that can be utilized for generating engineered bone. For the synthetic route, scaffold-ECM hybrid matrices are developed by culturing of cell-seeded scaffolds for a limited duration of time often under engineered culture conditions and subsequently scaffold-ECM hybrid matrices are obtained after decellularization to produce a biologically active matrix that can be used for engineering bone tissue.