Osteoinductive bone graft substitutes

Ludwig, Steven C.; Kowalski, Joseph M.; Boden, Scott D.

doi:10.1007/pl00008317

Cited by 60 publications

(53 citation statements)

References 49 publications

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“…27,28 With recent advances in the knowledge regarding the availability of osteoinductive and osteoproliferative proteins, we have entered into an era of biologic manipulation of bone formation. [29][30][31] Many studies showed that the combination of biocompatible bone implants and growth factors can provide a sufficient construct for an improved regeneration of bone defects. [32][33][34][35][36] Nevertheless, up to now no data were available about the biological activity of growth factors after release from bone scaffolds, what is inalienable for understanding the observed in vivo effects and for improving bone scaffolds as delivery systems of osteogenic growth factors in the future.…”

Section: Discussionmentioning

confidence: 99%

Biological activity of recombinant human growth factors released from biocompatible bone implants

Ziegler

Anger

Krummenauer

et al. 2007

J Biomedical Materials Res

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The present investigation was performed to study the bioactivity of osteoinductive and osteoproliferative growth factors after release from biocompatible bone implants. Three types of porous carriers were used in this study: hydroxyapatite, alpha tricalcium phosphate, and a neutralized glass ceramic. Implants were loaded with recombinant human bone morphogenetic protein 2 (rh-BMP-2) and recombinant human basic fibroblast growth factor (rh-bFGF) in a concentration of 2 microg/150 microL PBS each. The released growth factors were then applicated into SAOS-2-cell cultures. After 3, 5, and 7 days cell differentiation was measured by the activity of alkaline phosphatase (ALP), cell proliferation by using a MTT assay as well as a cell counter. Rh-BMP-2 released during the first hour from the scaffolds led to a significant increase of the activity of ALP in the incubated SAOS-2-cell culture after 3, 5, and 7 days. However, the incubation with rh-BMP-2 released after 24 h was not found to increase the expression of ALP. The incubation of cell cultures with rh-bFGF released during the first hour led to a significant increase of cell number and of extinction in the MTT assay, whereas this increase was not observed after incubation with rh-bFGF released after 24 h. The in vitro measured biological activity of released growth factors from the surface of synthetic implants is time-depending. If prolonged osteoinductive and osteoproliferative potency of growth factors is desired, a modified application technique should be chosen to stabilize those proteins.

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Section: Discussionmentioning

confidence: 99%

Biological activity of recombinant human growth factors released from biocompatible bone implants

Ziegler

Anger

Krummenauer

et al. 2007

J Biomedical Materials Res

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“…Starting with Grafton ™ gel (Osteotech Inc., Eatontown, NJ), which was the first commercially available DBM preparation with a glycerol carrier, Grafton ™ is also currently supplied as a malleable putty (Grafton ™ Putty) and as flexible strips (Grafton ™ Flex). Although most clinical studies advocate DBM as an excellent bone substitute with osteoconductive or osteoinductive properties, [7][8][9] some authors report a local aseptic inflammatory tissue reaction after in vivo application of DBM or other bone ceramic substitutes. 10 -12 In contrast to the large number of in vivo data, there is no cell-culture study published dealing with the biocompatibility of Grafton ™ Putty or Grafton ™ Flex material in comparison with other bone substitutes to date.…”

Section: Introductionmentioning

confidence: 99%

Extensive H⁺release by bone substitutes affects biocompatibilityin vitrotesting

Jäger

Fischer

Schultheis

et al. 2005

J Biomedical Materials Res

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Bone substitutes are widespread in orthopedic and trauma surgery to restore critical bony defects and/or promote local bone healing. Cell culture systems have been used for many years to screen biomaterials for their toxicity and biocompatibility. This study applies a human bone marrow cell culture system to evaluate the toxic in vitro effects of soluble components of different bone substitutes, which are already in clinical use. Different specimens of tricalcium phosphates (TCP) (Vitoss, Cerasorb), nondecalcified bovine bone (Lubboc), demineralized human bone matrices (DBM) (Grafton Flex/Putty), and collagen I/III matrix (ACI-Maix) were tested in Dulbecco's modified Eagle's medium (DMEM) and MesenCult culture solution and compared with a biomaterial-free cell culture. Biocompatibility parameters were cell viability evaluated by phase-contrast microscopy and laser flow cytometry, morphology, and the local H(+) release by bone substitutes. There were significant differences (p < 0.05) between the tested biomaterials and culture solutions. Collagen I/III, non-demineralized bovine bone, and TCP materials showed advantages for cell survival over other tested biomaterials (average values of vital cells/mL MesenCult/DMEM: Collagen I/III: 1090/1083; Vitoss: 893/483; Cerasorb: 471/523; Lubboc: 815/410; Grafton Putty: 61/44; Grafton Flex: 149/57). Especially the DBM materials lead to a significant decrease of pH, which is considered to be a major factor for cell death. DMEM culture solution supports cell survival for those bone substitutes that induce an alkaline reaction, whereas MesenCult media promotes cell vitality in biomaterials, which leads to an acidification of culture solution.

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“…[1][2][3][4]14,32,33 BMP-2 and -7 have been introduced clinically for treatment of open tibial fractures. 13,34,35 Although there is some appreciation of sequential expression of these potent GFs in fracture healing 2,3,19,20 and in single-type cell culture models, 14,[16][17][18] little is known about their associations with the final amount of bone formation during osteogenesis. Moreover, the knowledge on the relationships between the production levels of GFs during osteogenesis is limited as well.…”

Section: Introductionmentioning

confidence: 98%

The Sequential Production Profiles of Growth Factors and their Relations to Bone Volume in Ossifying Bone Marrow Explants

Gürkan

Gargac

Akkuş

2010

Tissue Engineering Part A

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Osteogenesis is a complex process that involves the synergistic contribution of multiple cell types and numerous growth factors (GFs). To develop effective bone tissue engineering strategies employing GFs, it is essential to delineate the complex and interconnected role of GFs in osteogenesis. The studies investigating the temporal involvement of GFs in osteogenesis are limited to in vitro studies with single cell types or complex in vivo studies. There is a need for platforms that embody the physiological characteristics and the multicellular environment of natural osteogenesis. Marrow tissue houses various cell types that are known to be involved in osteogenesis, and in vitro cultures of marrow inherently undergo osteogenesis process. Self-inductive ossification of marrow explants in vitro can be employed as a representative multicellular and three-dimensional model of osteogenesis. Therefore, the aims of this study were to employ the rat bone marrow explant ossification model to determine (1) the temporal production profiles of key GFs involved in osteogenesis, (2) the relation between GF production and ossification, and (3) the relations between the GF levels throughout ossification. Temporal production profiles of transforming GF beta-1 (TGF-beta1), bone morphogenetic protein-2 (BMP-2), vascular endothelial GF (VEGF), and insulin-like GF-1 (IGF-1) and the bone-related proteins alkaline phosphatase and osteocalcin were obtained by enzyme-linked immunosorbent assays conducted at days 2, 7, 12, 14, 19, and 21. The final amount of ossification (ossified volume [OV]) was measured by microcomputed tomography at day 21. TGF-beta1, BMP-2, VEGF, IGF-1, alkaline phosphatase, and osteocalcin were produced by the ossifying marrow explants differentially over time. The early production of IGF-1 (day 2) correlated positively (r = 0.868) with OV; however, latent production of IGF-1 correlated negatively (day 14: r = -0.813; day 19: r = -0.865) with OV. OV also correlated with VEGF levels at day 12 (r = 0.988) and at day 14 (r = 0.970). Production of GFs also correlated to each other across time points, which indicates the complex and interconnected contribution of various GFs in osteogenesis. Therefore, tissue engineering strategies toward bone regeneration should consider the richness of GFs involved in osteogenesis and their dynamically varying participation over time.

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Osteoinductive bone graft substitutes

Cited by 60 publications

References 49 publications

Biological activity of recombinant human growth factors released from biocompatible bone implants

Biological activity of recombinant human growth factors released from biocompatible bone implants

Extensive H⁺release by bone substitutes affects biocompatibilityin vitrotesting

The Sequential Production Profiles of Growth Factors and their Relations to Bone Volume in Ossifying Bone Marrow Explants

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Osteoinductive bone graft substitutes

Cited by 60 publications

References 49 publications

Biological activity of recombinant human growth factors released from biocompatible bone implants

Biological activity of recombinant human growth factors released from biocompatible bone implants

Extensive H+release by bone substitutes affects biocompatibilityin vitrotesting

The Sequential Production Profiles of Growth Factors and their Relations to Bone Volume in Ossifying Bone Marrow Explants

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Product

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Extensive H⁺release by bone substitutes affects biocompatibilityin vitrotesting