The impact of immune response on endochondral bone regeneration

Schematic overview of the cell types involved in the endochondral ossification process induced by an allogeneic tissue engineered construct and the immune response elicited. After implantation, the phenotype of MSC-derived chondrocytes progresses until the late hypertrophic stage, a stage that is characterized by increased secretion of proangiogenic factors and MMPs to promote matrix remodeling and new bone formation. However, the implantation of a biomaterial, together with the presence of allogeneic cells, at the same time induces the recruitment of host immune cells. In particular, the immune response against the carrier biomaterial (left panel) is mainly characterized by the presence of cells from the innate branch of the immune system while the presence of allogeneic cells triggers mostly an adaptive response (right panel). Nonetheless, the recruited cells can influence each other through the engagement of common players (e.g., dendritic cells and the complement system) and through the secretion of soluble factors such as cytokines that can promote the induction of a pro-inflammatory or anti-inflammatory environment. The final outcome of the bone regeneration process is determined by the balance between the promotion of endochondral ossification and the exacerbation of the immune response by the allogeneic construc