In addition, VEGF is necessary for a specific bone regeneration pathway called intramembranous ossification, where mesenchymal tissue is directed towards bone formation. This involves the direct differentiation of bone progenitors to osteoblasts (contrary to a cartilage intermediate in endochondral ossification). Many primary literature papers have demonstrated that a loss-of-function experiment against VEGF in the osteoblast precursors significantly reduces ossification in craniofacial bone structures,[27][28][29] highlighting the essential role of VEGF in craniofacial regeneration.