Enhancement of bone ingrowth by transforming growth factor-beta.

Sumner, Dale R.; Turner, Thomas M.; Purchio, A. F.; Gombotz, Wayne R.; Urban, Robert M.; Galante, Jorge O.

doi:10.2106/00004623-199508000-00001

Cited by 197 publications

(119 citation statements)

References 74 publications

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“…54 Several biological factors, such as TGFb, BMP, FGF, PDGF, IGF, and LMP-1, have been investigated for their potential use in bone regeneration and skeletal repair. [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] BMPs have been shown to be the most promising, and clinical trials with recombinant BMP-2 and -7 are ongoing. 54,[70][71][72][73] These BMPs have shown varying degrees of success in the clinical setting and further study on their mechanisms of action and optimal formulations is required to optimize effectiveness of this strategy for promoting osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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“…TGF-β is produced by osteoblasts and is stored in the bone matrix, making bone the largest reservoir of TGF-β in the body [ Whereas BMPs induce bone in heterotopic sites, stimulation of bone formation by TGF-β depends on orthotopic application, for example, subperiosteal injection [65]. TGF-β1 enhances the healing of experimentally created defects of the skull in rabbits [11,47] and bone ingrowth in porous titanium rods [64] and tricalcium phosphate coated implants in dogs [40].…”

Section: Tgf-βmentioning

confidence: 99%

Growth factors in bone

Solheim¹

1998

International Orthopaedics

171

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“…Although some encouraging results have been reported [4][5][6], a major drawback with the adsorption method is that it provides little, if any, control over delivery, including retention and orientation, of molecules. Proteins are initially retained on the surface by weak physisorption forces, and then, depending on the implant microenvironment, which varies among anatomical sites and among patients, the molecules desorb from the surface in an uncontrolled manner to interact with cells.…”

Section: Introductionmentioning

confidence: 99%

Immobilization of glycoproteins, such as VEGF, on biodegradable substrates

Sharon

Puleo

2008

Acta Biomaterialia

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Attachment of growth factors to biodegradable polymers, such as poly(lactide-co-glycolide) (PLGA), may enhance and/or accelerate integration of tissue engineering scaffolds. Although proteins are commonly bound via abundant amino groups, a more selective approach may increase bioactivity of immobilized molecules. In this research, exposed carboxyl groups on acid-terminated PLGA were modified with dihydrazide spacer molecules. The number of hydrazide groups available for subsequent attachment of protein was dependent on dihydrazide length, with shorter molecules present at significantly greater surface densities. The potent angiogenic glycoprotein vascular endothelial growth factor (VEGF) was oxidized with periodate and the aldehyde moieties allowed to react with the hydrazide-derivatized PLGA. Derivatization initially affected the amount of protein bound to the surfaces, but differences were substantially reduced following overnight incubation in saline. More importantly, use of shorter dihydrazide spacers significantly enhanced accessibility of immobilized VEGF for binding neutralizing antibody and soluble VEGR receptor. Furthermore, immobilized growth factor enhanced endothelial cell proliferation, with surfaces having the shortest and longest spacers stimulating greater effects. The present work has not only demonstrated an alternative approach to immobilizing growth factors on biodegradable materials, but the scheme can be used to alter the amount of protein bound as well as its availability for subsequent biointeractions.

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Enhancement of bone ingrowth by transforming growth factor-beta.

Cited by 197 publications

References 74 publications

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

Growth factors in bone

Immobilization of glycoproteins, such as VEGF, on biodegradable substrates

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