## 2 Bone Grafting Physiology  
The integration of a bone graft is conditioned by three distinct processes: osteoinduction, osteoconduction and osteogenic capacities. Depending on the type of graft, these processes may interfere or may not be present one or another.  
_Osteoconduction_ is the process of the ingrowth of the host capillaries, connective tissue and mesenchymal stem cells (MSCs) in an implanted scaffold with a structure similar to that of host bone. Consequently to this ingrowth process, the graft is incorporated into the host's bone [4]. There are different models of this process according to the type of implanted scaffold. For fresh bone autograft, osteoconduction is facilitated by associated osteoinduction. Allograft is treated mechanically (removal of soft tissues), chemically (ethanol) and physically (gamma radiation) in order to sterilize it, so any osteogenic and osteoinductive properties are compromised. For this kind of graft, osteoconduction is the main process of integration, similar to synthetic bone substitutes which lack osteoinductive factors as well [5]. The difference between nonviable biologic scaffolds and synthetic structures is about the speed of integration, which is higher for the first ones.  
_Osteoinduction_ represents the recruiting process of the MSCs from the host in order to differentiate into chondroblasts and osteoblasts, which produce new bone by endosteal ossification. Osteoinduction is initiated and controlled by exogenous growth-factors, natural proteins or hormones that stimulate cellular differentiation, proliferation and growth [6]. The most important are -2, -4 and -7 bone morphogenetic proteins (BMP); platelet derived growth factor (PDGF); interleukins; fibroblast growth factors (FGF); granulocyte-macrophage colony-stimulating factors; and vascular endothelial growth factor (VEGF) [7].  
_Osteogenic capabilities_ of bone grafts are their ability to synthesize new bone by donor cells from either the host or graft donor; the cells involved are MSCs, osteoblasts and osteocytes. Only fresh autologous grafts or allografts and bone marrow have this property [6]. Cancellous bone has more osteogenic elements compared with cortical bone, so the osteogenic capabilities are higher.  
Bone graft incorporation has two phases: the first phase is represented by the formation of hematoma at the level of the graft-host tissue interface, and the release of inflammatory factors (cytokines and growth factors) at this level, responsible for recruitments of MSCs and macrophages; the second stage is represented by inflammatory processes with the development of fibrovascular tissue. Due to their structural difference and the vascularization of cancellous and cortical bone, the speed and the amount of integration is can differ.  
For cancellous autograft, the necrotic graft tissue is slowly removed by the macrophages, a neovascularization is developed, and the osteoblasts derived from MSCs are aligned at the host graft interface, producing osteoid. After a complex process that takes 6 to 12 months, this osteoid is mineralized, which generates new bone [6]. For cancellous allograft, the inflammatory response of the host produces a fibrous layer around the graft, making it more challenging for the surrounding bone host to deposit new osteoid and bone at this level [7].  
The mechanism of cortical bone incorporation, mediated predominantly by osteoclasts as opposed to osteoblasts, is defined as creeping substitution. This process of almost complete resorption of the graft, with simultaneous deposition of new, viable bone, begins at the graft-host tissue interface, progressing along the long axis of the cortical graft. It is defined by a quick loss of mechanical strength of the graft in the initial period of resorption and a long period (years) before completion [8].