Recombinant human epidermal growth factor(Kyung Hee University)

Objectives: The delivery of growth factors for enhanced osseointegration depends on the effectiveness of the carrier systems at the bone–implant interface. This study evaluated the effect of solo and dual delivery of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF165) from biomimetically octacalcium phosphate‐coated implants on osseointegration.Materials and methods: Biomimetic implants, bearing either a single growth factor (BMP or VEGF) or their combination (BMP+VEGF), were established, and compared with acid‐etched (AE, control) and biomimetic implants without growth factor (CAP). Implants were placed into frontal skulls of nine domestic pigs. The quality of osseointegration was evaluated using microradiographic and histomorphometric analysis of bone formation inside four defined bone chambers of the experimental implant at 1, 2 and 4 weeks.Results: Biomimetic implants, either with or without growth factor, showed enhanced bone volume density (BVD) values after 2 and 4 weeks. This enhancement was significant for the BMP and BMP+VEGF group compared with the control AE group after 2 weeks (P<0.05). All biomimetic calcium‐phosphate (Ca‐P) coatings exhibited significantly enhanced bone–implant contact (BIC) rates compared with the uncoated control surface after 2 weeks (P<0.05). However, the combined delivery of BMP‐2 and VEGF did not significantly enhance BIC at the final observation period.Conclusion: It was concluded that the combined delivery of BMP‐2 and VEGF enhances BVD around implants, but not BIC. Therefore, it may be assumed that changes in the surface characteristics should be considered when designing growth factor‐delivering surfaces.To cite this article: 
Ramazanoglu M, Lutz R, Ergun C, von Wilmowsky C, Nkenke E, Schlegel K A. The effect of combined delivery of recombinant human bone morphogenetic protein‐2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium‐phosphatecoated implants on osseointegration.
Clin. Oral Impl. Res. xx, 2011; 000–000.
doi: 10.1111/j.1600‐0501.2010.02133.x

The hemolymphopoietic growth factors, including the colony-stimulating factors (CSF) and interleukins (IL), are described and categorized on the basis of their biological features in laboratory systems. Although these agents are varied and exceptions exist, in general they lack lineage specificity although they may express lineage-predominant activity. They act at multiple levels of hemolymphopoietic cell differentiation, demonstrate additive or synergistic effects when combined in vitro, require surface receptors on target cells to directly express their activity, and may be produced by a variety of cells. This framework of behavioral generalizations, completed by the specifics of each factor's activity, despite the artifactual and simplified nature of in vivo systems, forms the basis for concepts of in vitro activity and for clinical applications. Hemolymphopoietic growth factors studied in the clinic have demonstrated impressive and important activity, validating much of the in vitro data. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have clearly reduced neutropenia and infection rates when administered following conventional chemotherapy and high-dose chemotherapy followed by autologous bone marrow transplantation. To a varying degree, similar results with G-CSF and/or GM-CSF have been described in other diseases including acute myelogenous leukemia (AML) treated following induction chemotherapy, myelodysplastic syndrome, hairy cell leukemia, aplastic anemia, and chronic neutropenias. In preliminary studies IL-3 has been shown to have similar qualitative activities. However, these agents have not demonstrated a reproducible salutary impact on platelet or red cell lineages. Adverse effects on platelet counts and/or platelet recovery have been noted. Additionally, hemolymphopoietic growth factor receptors have been identified on malignant cells, suggesting that these factors could stimulate neoplastic growth. Studies with GM-CSF and IL-3 have demonstrated blast proliferation in some cases of AML and myelodysplasia, underscoring the capacity of these agents to stimulate the growth of myeloid leukemia. No clinically evident impact of these factors upon the growth of solid tumors has been identified but this issue has not been adequately studied. The toxicity of these agents has been surprisingly limited and appears to be related to their biologic activities. Hemolymphopoietic growth factors as single agents have broad clinical applications in cytopenias. Several methods for enhancing the clinical activity of these agents are under study, including the use of combinations of growth factors synergistic in vitro.