PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration

Chang, Ping-Chuan; Seol, Yang‐Jo; Cirelli, Joni Augusto; Pellegrini, G; Jin, Qiming; Franco, Lea M.; Goldstein, Steven A.; Chandler, Lois A.; Sosnowski, Barbara A.; Giannobile, William V.

doi:10.1038/gt.2009.117

Cited by 93 publications

(89 citation statements)

References 36 publications

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“…Among them, there are fibroblast growth factor-2 (FGF-2), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), TGF-b, and vascular endothelial growth factor A (VEGFA). [5][6][7][8][9][10][11] However, little is known about their bone regeneration capacity relative to BMP-2.…”

Section: Introductionmentioning

confidence: 99%

A Comparative Analysis of the Osteogenic Effects of BMP-2, FGF-2, and VEGFA in a Calvarial Defect Model

Behr

Sorkin

Lehnhardt

et al. 2012

Tissue Engineering Part A

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The utilization of growth factors for bone regeneration is a widely studied field. Since the approval of bone morphogenetic protein-2 (BMP-2) for therapeutic use in humans, the concept of utilizing growth factors for bone regeneration in translational medicine has become even more attractive. Despite many studies published on individual growth factors in various bone models, comparative analysis is largely lacking. The aim of our study was to compare three different proosteogenic factors under identical in vivo conditions. Thus, we tested the bone regeneration capacity of the three different growth factors BMP-2, fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor A (VEGFA) in a calvarial defect model. We demonstrated that BMP-2 and VEGFA had similar bone healing capacities, resulting in complete calvarial healing as early as week 3. FGF-2 also showed a significantly higher bone regeneration capacity; however, the healing rate was lower than with BMP-2 and VEGFA. Interestingly, these findings were paralleled by an increased angiogenic response upon healing in BMP-2-and VEGFA-treated calvarial defects as compared with FGF-2. Immunohistochemistry for proliferating and osteoprogenitor cells revealed activity at different points after surgery among the groups. In conclusion, we demonstrated an efficient bone regeneration capacity of both BMP-2 and VEGFA, which was superior to FGF-2. Moreover, this study highlights the efficient bone regeneration of VEGFA, which was comparable with BMP-2. These data provide a valuable comparative analysis, which can be used to further optimize growth factor-based strategies in skeletal tissue engineering.

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Section: Introductionmentioning

confidence: 99%

A Comparative Analysis of the Osteogenic Effects of BMP-2, FGF-2, and VEGFA in a Calvarial Defect Model

Behr

Sorkin

Lehnhardt

et al. 2012

Tissue Engineering Part A

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“…Upotreba matičnih ćelija masnog tkiva može biti brzo sprovedena, čak u roku od 24 sata, zahvaljujući posebnoj metodi tkivnog inžinjeringa i daje pozitivne rezultate u zarastanju koštanih defekata 48 . Osim zarastanja rane, neki autori predlažu i upotrebu faktora rasta u lečenju alveolita 49 , bolju oseointegraciju implanata 50 , augmentaciju alveolarnog grebena 51 . Postoje podaci da je postoperativno zarastanje bilo bolje kao i da je postoperativni bol slabiji kod pacijenata tretiranih faktorima rasta bogatim plazmom 52 .…”

Section: Primena Faktora Rasta U Zarastanju Ekstrakcione Raneunclassified

“…The fat tissue stem cells application can be carried out as promptly as within 24 hours owing to a special method of tissue engineering, and has positive results in healing bone defects 48 . In addition to wound healing, some authors propose the use of growth factors in the treatment of alveolitis 49 , implant osseointegration 50 and alveolar ridge augmentation 51 . There is evidence that the postoperative healing was better and postoperative pain lower in patients treated with growth-factors-rich plazma 52 .…”

Section: The Use Of Growth Factors In Extraction Wound Healingmentioning

confidence: 99%

The role of growth factors in extraction wound healing

Stojanović¹,

Tijanić²,

Jovanović³

et al. 2015

Acta stomatologica Naissi

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SažetakZarastanje rane je složeni proces koji uključuje hemostazu, inflamaciju, proliferaciju i remodelaciju tkiva. Faktori rasta su prirodni biološki posrednici koji regulišu najznačajnije ćelijske procese uključene u regeneraciju tkiva, kao što su DNA sinteza, angiogeneza, metabolička aktivnost, migracija, hemotaksa, proliferacija, diferencijacija UvodZarastanje rane je složeni proces koji uključuje hemostazu, inflamaciju, proliferaciju i remodelaciju tkiva. U procesu zarastanja rane učestvuju različiti tipovi ćelija, složena signalizaca događaja i brojni faktori rasta.Faktori rasta su prirodni biološki posrednici koji regulišu najznačajnije ćelijske procese uključene u regeneraciju tkiva, kao što su DNA sinteza, angiogeneza, metabolička aktivnost, migracija, hemotaksa, proliferacija, diferencijacija i sinteza matriksa. Faktori rasta su ćelijski specifični, što znači da svaki faktor deluje na određenu vrstu ćelija 1 . Najznačajniji faktori rasta koji učestvuju u zarastanju ekstrakcione rane i regeneraciji koštanog tkiva su: 1. trombocitni faktor rasta -PDGF; 2. transformacioni faktor rasta -TGF β superfamilija; 3. insulinu sličan faktor rasta -IGF; 4. koštani morfogenetski proteini -BMP -2, BMP -7 ; 5. vaskularni endotelijalni faktor rasta -VEGF; 6. fibroblastni faktor rasta -FGF;Polipeptidni faktori rasta ispoljavaju svoje dejstvo vezujući se za target ćelije preko svojih aktivnih krajeva "dimera" za tirozinkinazu, transmembranski receptor na površini ćelijske membrane 2 . Aktivirani T-K transmembranski receptor pokreće energetsku aktivnost ćelije podizanjem intracelularne koncentracije cirkularnog adenozin-monofosfata i dovodi do oslobađanja intracitoplazmatičnih proteina prenosioca signala. Oslobođeni od transmembranskih receptora tirozin-kinaze, proteini prenosioci signala odlaze do nukleusa, gde otključavaju specifičnu genetsku sekvencu za kontrolu ćelijske funkcije i indukciju ekspresije normalne genetske aktivnosti.Povreda tkiva praćena je inflamatornim odgovorom, aktiviranjem komplemenata i oštećenjem krvnih sudova koje uzrokuje krvaranje. Posle povrede tkiva, pokreće se kaskadni proces koagulacije krvi koji vodi u formiranje fibrinske mreže kao osnove za nakupljanje uobličenih krvnih elemenata. Na mestu povrede tkiva dolazi do adhezije i agregacije trombocita, a njihovom degranulacijom oslobađaju se mnogobrojni glikoproteini i faktori rasta kao što su faktor rasta poreklom iz trombocita (PDGF), epidermalni faktor rasta (EGF), transformišući faktor rasta beta (TGF-β), vaskularni endotelijalni faktor rasta (VEGF) i bazni fibroblastni faktor rasta (bFGF) 3,4 . Мnoštvo faktora rasta oslobođenih tokom hemostaze ima različite uloge, uključujući

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“…70 Moreover, it has been implicated in the formation of new bone in several in vivo studies. [71][72][73][74][75][76] Interestingly, fully differentiated macrophages cultured on Fg also evidenced enhanced secretion of angiogenic-associated proteins. This suggests that when triggered by Fg, macrophages influence different key steps, are able to modulate the inflammatory response, and also contribute to new bone formation and angiogenesis, both of which were stimulated with Fg-adsorbed Ch scaffolds in vivo.…”

Section: Figmentioning

confidence: 99%

Adsorbed Fibrinogen Enhances Production of Bone- and Angiogenic-Related Factors by Monocytes/Macrophages

Maciel

Oliveira²,

Colton

et al. 2014

Tissue Engineering Part A

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Macrophages are phagocytic cells with great importance in guiding multiple stages of inflammation and tissue repair. By producing a large number of biologically active molecules, they can affect the behavior of other cells and events, such as the foreign body response and angiogenesis. Since protein adsorption to biomaterials is crucial for the inflammatory process, we addressed the ability of the pro-inflammatory molecule fibrinogen (Fg) to modulate macrophage behavior toward tissue repair/regeneration. For this purpose, we used chitosan (Ch) as a substrate for Fg adsorption. Freshly isolated human monocytes were seeded on Ch substrates alone or previously adsorbed with Fg, and allowed to differentiate into macrophages for 10 days. Cell adhesion and morphology, formation of foreign body giant cells (FBGC), and secretion of a total of 80 cytokines and growth factors were evaluated. Both substrates showed similar numbers of adherent macrophages along differentiation as compared with RGD-coated surfaces, which were used as positive controls. Fg did not potentiate FBGC formation. In addition, actin cytoskeleton staining revealed the presence of punctuate F-actin with more elongated and interconnecting cells on Ch substrates. Antibody array screening and quantification of inflammation-and wound-healing-related factors indicated an overall reduction in Ch-based substrates versus RGD-coated surfaces. At late times, most inflammatory agents were downregulated in the presence of Fg, in contrast to growth factor production, which was stimulated by Fg. Importantly, on Ch + Fg substrates, fully differentiated macrophages produced significant amounts of macrophage inflammatory protein-1delta (MIP-1d), platelet-derived growth factor-BB, bone morphogenetic protein (BMP)-5, and BMP-7 compared with Ch alone. In addition, other important factors involved in bone homeostasis and wound healing, such as growth hormone, transforming growth factor-b3, and insulin-like growth factor-binding proteins, as well as several angiogenic mediators, including endocrine gland-derived vascular endothelial factor, fibroblast growth factor-7, and placental growth factor, were significantly promoted by Fg. This work provides a new perspective on the inflammatory response in the context of bone repair/regeneration mediated by a pro-inflammatory protein (Fg) adsorbed onto a biomaterial (Ch) that does not otherwise exhibit osteogenic properties.

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PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration

Cited by 93 publications

References 36 publications

A Comparative Analysis of the Osteogenic Effects of BMP-2, FGF-2, and VEGFA in a Calvarial Defect Model

A Comparative Analysis of the Osteogenic Effects of BMP-2, FGF-2, and VEGFA in a Calvarial Defect Model

The role of growth factors in extraction wound healing

Adsorbed Fibrinogen Enhances Production of Bone- and Angiogenic-Related Factors by Monocytes/Macrophages

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