**3. Bone graft healing mechanism**

The main component of bone healing is the selection of the materials for the bone graft. Bone grafts have different bone-forming capacities; therefore, we need to understand the mechanisms of bone regeneration for the grafts used at the recipient regions. The requirement of the region can be determined in advance and the graft is chosen accordingly. Bone healing in the region where the graft is placed is supported through osteogenic, osteoconductive, and/or osteoinductive mechanisms.

#### **3.1. Osteogenesis**

Osteogenesis is defined as the formation of bone in the region where osteoblasts and osteoblast precursors do not have bone tissue. New bone formation occurs when osteoblasts and osteoblast precursors are produced by cancellous bone and bone marrow. Osteogenesis (bone formation) is characterized by the presence of living osteoblast cells in the graft material. The only bone graft with osteogenesis is the autogenous bone [20]. Autogenous bone grafts, also called autografts, are grafts transplanted from one site to another. The most effective type in terms of osteogenesis is cancellous bones, due to the migration of bone cells at high concentrations. Autografts have been observed to have bone formation capacity even when bone tissue is placed underneath the skin [21]. Vascularization of the graft site is necessary for continued osteogenesis. Some studies have reported loss of osteogenic properties of free autogenous grafts without vascular support within 5 days and that they continued osteoinductive and osteoconductive effects at the end of the study [20, 21]. Therefore, free autogenous bone grafts show osteogenic characteristics only for a few days. We should pay attention to the viability of the cells when placing the autogenous graft in the recipient region. Once the autogenous bone has been obtained, it should not be left in the dry area, and if possible, it should be used as soon as possible with saline in a sterile environment [22].

#### **3.2. Osteoinduction**

Osteoinduction is an active process in which the bone graft causes the bone-forming cells to penetrate the recipient region and stimulates them to form new bones. Osteoinduction refers to the ability of the graft to send a signal to attract, proliferate, and differentiate early-lineage cells (e.g., mesenchymal stem cells or osteoprogenitor cells) into bone-forming cells, resulting in the formation of a mineralized bone. Bone morphogenetic proteins (BMPs) support these signals. BMP is measured as the amount of picograms in the normal bone. In recent studies on osteoinduction, Urist et al. isolated BMP, a soluble glycoprotein. They described BMP as a growth factor of the transforming growth factor (TGF)-β family and as an inductive agent. They also reported that at least 15 different types of BMPs were found, and the most important were BMP-2 and BMP-7 [23]. BMP is naturally released during trauma or the regeneration process and acts as an osteoinductive agent.

the cells and blood vessels can reach the receiving region. The vascular support in the organization of the cancellous bone in the graft is 30% better than that in the cortical bone [26].

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Prostheses that are supported on maxillary dental implants are now the optimum way to give patients an admissible quality of life. In cases with a vertical insufficient alveolar bone, a maxillary sinus lift with a bone graft using a crestal or lateral approach is needed. Elevation of the sinus floor permits the correct number and length of endosseous implants to be applied

Previous studies proved that dental implants related to maxillary sinus augmentation have a satisfactory long-term success and survival rate [28]. Implant application may be simultaneously combined with maxillary sinus lifting procedure as a" one-stage" surgery, or sinus lifting may be conducted at first, and implants are then applied as a" two-stage" operation. There are many options for graft material to augment the maxillary sinus. Autogenous grafts can be harvested from the chin and ramus intraorally or iliac crest, calvarium, and tibia extraorally. The disadvantages of autogenous grafts are resorption rate and morbidity. Allografts (cadaveric bone) are harvested and different techniques such as irradiation and freeze-drying are used to reduce antigenicity. Allografts are found in tissue banks. Xenografts consist of anorganic bovine or equine bone. The organic components of these types of grafts are chemically removed and a mineral scaffold is obtained. Alloplasts are synthetic materials; there are many types of structures of alloplastic grafts such as micro- or macroporous, dense, amorphous, or crystalline grafts. Structure and porosity directly influence the performance of the material [29].

Following tooth extraction, alveolar bone remodeling begins by means of vertical and/or horizontal bone resorption [30] so that a proper prosthetic and esthetic position of dental implants can be influenced. Alveolar socket preservation techniques have been introduced to conserve

• In cases where implant placement needs to be postponed for >6 months for some reason;

There are various graft materials used in socket preservation surgery such as autografts, allografts, xenografts, alloplasts, or platelet concentrates. Allogenic bone is described as the

• Implant placement needs to be delayed for patient- or site-related reasons;

for adequate mechanical support of the atrophic posterior maxilla [27].

**4. Bone augmentation techniques**

**4.1. Sinus lifting**

**4.2. Socket preservation**

and

the alveolar bone vertically and horizontally [31].

Socket preservation could be considered when:

• If partially fixed pontic site is planned [32].

Demineralized bone matrix (DBM) allograft materials have osteoinductive healing mechanisms. DBM allografts can provide a matrix for bone cells to infiltrate and produce bone. Its healing mechanism manifests through osteoinductive pathways, and bioactive molecules stimulate mesenchymal cells to differentiate into bone-forming cells [24].

#### **3.3. Osteoconduction**

Osteoconduction is described as the growth of a superficial bone on a surface. Osteoconductive materials are biocompatible and have an osteoconductive surface: on its pores, in its ducts, or in its tubes. Materials with osteoconductive properties form a matrix and guide osteogenesis. Grafts with osteoconductivity have no bone formation capacity and can only function as a roof for bone formation. If osteoconductive materials are placed in ectopic areas such as subcutaneous bones, bone formation does not occur and the material remains unchanged or resurfaced [22]. Examples of osteoconductive properties are autografts, allografts, xenografts, calcium sulfates, calcium phosphate cements, ceramics, collagen, and synthetic polymers. It is also known that bone graft materials may be supplemented with materials such as exogenous growth factors, to create inductive effects [22].

#### **3.4. Creeping substitution**

Creeping substitution indicates the movement of new tissues through channels made by blood vessels invading a transplanted bone. The dynamic healing and reconstructive process of bone transplantation was described by Axhausen in 1907; he reported that bone transplants undergo necrosis. The necrotic bone is then replaced by the new bone via creeping substitution [25].

Improvement of the graft material differs according to graft type in terms of duration and content. Vascular support in the recipient region and the survival rate of cells in the graft have a direct impact on graft recovery. Morphologically, the cortical bone, which is the tight structure around the haversian and Volkmann channels, consists of circular, parallel, and interstitial bone lamellar. The cancellous bone is porous and trabecular in shape and contains the bone marrow. There is a less surface area in the cortical bone than in the cancellous bone; therefore, the cells and blood vessels can reach the receiving region. The vascular support in the organization of the cancellous bone in the graft is 30% better than that in the cortical bone [26].
