Schematics showing mechanisms of bone regeneration by immature osteoblasts. (A) Structures of the osteoblasts seeded scaffold constructs in the bone defect area following transplantation and healing of the defect site. (B) Molecular mechanism of bone remodeling by immature osteoblast. The immature osteoblasts under the influence of various cytokines such BMP2, SHH secreted from the bone matrix differentiate into osteoblasts. These osteoblasts produce various cell products, including enzymes alkaline phosphatase and collagenase, growth factors, osteocalcin, and collagen, part of the organic unmineralized component of bone. Few osteoblasts embed inside matrix to become osteocyte and others remain as a bone lining cells on the outer surface. Consequently, when osteoblasts lay down new matrix the osteoclast will differentiate from circulating monocytes/macrophages induced from osteoblasts secreted cytokines such as RANKL and M-CSF, as an inflammatory response to the bone defect from Osteoblasts. Simultaneously, angiogenic factors including VEGF are released from the osteoblasts to form new blood vessels.