Close-to-native bone repair via tissue-engineered endochondral ossification approaches

In order to solve the clinical challenges related to bone grafting, several tissue engineering (TE) strategies have been proposed to repair critical-sized defects. Generally, the classical TE approaches are designed to promote bone repair via intramembranous ossification. Although promising, strategies that direct the osteogenic differentiation of mesenchymal stem/stromal cells are usually characterized by a lack of functional vascular supply, often resulting in necrotic cores. A less explored alternative is engineering bone constructs through a cartilage-mediated approach, resembling the embryological process of endochondral ossification. The remodeling of an intermediary hypertrophic cartilaginous template triggers vascular invasion and bone tissue deposition. Thus, employing this knowledge can be a promising direction for the next generation of bone TE constructs. This review highlights the most recent biomimetic strategies for applying endochondral ossification in bone TE while discussing the plethora of cell types, culture conditions, and biomaterials essential to promote a successful bone regeneration process.