**11. Growth factors in bone regeneration**

augmentation followed by using classic GBR procedure to restore the remaining defects

**Figure 19.** A, The atrophic ridge of posterior mandible is selected as the recipient site. B, Lateral ramus bone graft is harvested as an OBG. C, The OBG is fixed to augment the defect vertically. D, Bone materials are used to reconstruct

Approximately after 6 months the surgical site is ready to install the implant fixtures. The average bone gain presented in the literature is 4.3 mm after performing this procedure [43]. **Indications.** This procedure is suitable for small to moderate defects in partial edentulous patients. This technique is usually indicated in combined defects to reconstruct horizontal and

**Advantages.** This procedure can be performed under local anesthesia. This technique removes

**Disadvantages.** This technique is not for large defects. The high failure rate of this technique

Although the autograft is accepted as the gold standard for the treatment of bone defects, some drawbacks of autogenous bone grafts such as limited graft accessibility, prolonged operation time and donor site morbidity as well as high costs, continue to drive the quest for development of alternative methods for bone regeneration and repair. Three new strategies are recently

**Stem cell therapy**; the transplantation of cultured osteogenic cells from host tissues like bone

the horizontal defect by GBR procedure. E, The surgical site is ready for insertion of implant fixtures.

vertical defects. The common indication of this technique is in the anterior maxilla.

the need for harvesting extraoral bone grafts and reduces discomfort of the patient.

in posterior of mandible is one of the major drawbacks of this technique [54].

**10. Regenerative cell therapy**

undergoing investigation:

marrow.

(Figure 19).

534 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

Protein therapy has demonstrated the most practical promise, mainly incorporating osteoinductive morphogens. Several osteoinductive cytokines have been suggested and investigated in the literature including bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and transform‐ ing growth factor beta (TGF-β). Bone morphogenetic proteins have the most experimental and practical potential. Some studies however have shown the efficacy of other growth factors on bone reconstruction[55]. Synergic effects of two or more growth factors have been evaluated in some studies [56, 57].

**Bone morphogenic proteins (BMPs).** BMP is a large family of growth factors released naturally from different human tissues and acts in regenerating bone and cartilage tissue. The efficacy of BMP has been evaluated in several investigations [58-60]. After producing recombi‐ nant human BMP (rhBMP) the use of this cytokine became more popular in clinical studies. BMP can be applied in the surgical site by a carrier namely absorbable collagen sponge (ACS) or poly lactic glycolic acid (PLGA). The positive influence of BMP on bone regeneration in defects of the oral and maxillofacial area has been shown in most studies [55].

**Platelet-derived growth factor (PDGF).** PDGF promotes new bone formation. This facilitating bone regeneration factor is suggested to be used in maxillofacial defects where bone grafting is needed [61, 62]. PDGF improves the new bone formation by three main methods including mitogenesis, angiogenesis macrophage activation. The major role of PDGF is in differentiation of pre-osteoblasts to osteoblasts and proliferation of mesenchymal stem cells (MSCs). The usual carrier for PDGF has a mineral part in most investigations [55].

**Vascular endothelial growth factor (VEGF).** VEGF is an angiogenic factor which usually is released in response to hypoxia or tissue damage. VEGF has been used in different studies with both polymeric scaffolds and ceramic carriers [63, 64]. This growth factor is sometimes applied in combination with other promoting factors like BMP and PDGF to improve it's the regenerative features [65-67]. Despite all the important roles of VEGF investigated and presented in the literature most studies showed that this growth factor is less inductive than BMP in bone regeneration [55.[

**Basic fibroblast growth factor (bFGF).** bFGF is an important growth factor in wound healing, formation of granulation tissue and remodeling [68]. Several studies evaluated the effect of bFGF in bone regeneration; however its role is not as important as other factors like BMP [55].

**Transforming growth factor beta (TGF-β).** TGF-β is a group of proteins released from several tissues including macrophages and plays an important role in healing. The bone regenerative features of rhTGF- β1, rhTGF-β2, and TGF-β3 have been evaluated in different investigations. The usual carrier for the delivery of this growth factor in these studies is a gelatinous matrix. Some of these researches have shown the positive influence of this growth factor in bone regeneration [55].

**Indications.** The most common usage of growth factors is in implant surgery. The defects created during the procedure or post-operative bone dehiscences may be corrected with the application of growth factors. **Advantages.** Growth factors are presented as an alternative for bone grafts in reconstruction of maxillofacial defects. These proteins reduce the morbidity of the patients by removing the need of harvesting bone grafts. These factors are responsible for the major events in regeneration including angiogenesis, cell differentiation, mitogenesis, and bone formation [69]. Furthermore the combination of these proteins with bone grafts promotes the generation of new bone and facilitates healing of the defects.

**Disadvantages.** The high costs of producing growth factors are the major limitations for using these materials in humans. Production of recombinant growth factors as rhBMP and rhPDGF requires a period of time and high costs [70]. Application of growth factures is very technique sensitive and the clinician should be an expert in this procedure. Choosing a slow releasing scaffold is still a challenge among surgeons to use with the growth factor as a carrier. The appropriate dosage and useful concentration of these proteins in bone regeneration is another controversial issue which should be resolved. The excess amount of growth factor or wrong application of them may lead to ectopic bone formation and result in insufficient correction of the deficiencies.
