Dataset Information

Sustained and localized in vitro release of BMP-2/7, RANKL, and tetracycline from FlexBone, an elastomeric osteoconductive bone substitute.

ABSTRACT: We tested the hypothesis that synthetic composites containing a high percentage of osteoconductive biominerals well-integrated with a hydrophilic polymer matrix can be engineered to provide both the structural and biochemical framework of a viable synthetic bone substitute. FlexBone, an elastic hydrogel-mineral composite exhibiting excellent structural integration was prepared by crosslinking poly(2-hydroxyethyl methacrylate) hydrogel in the presence of 25 wt% nanocrystalline hydroxyapatite and 25 wt% tricalcium phosphate. Biologically active factors tetracycline, BMP-2/7, and RANKL that stimulate bone formation and remodeling were encapsulated into FlexBone during polymerization or via postpolymerization adsorption. SEM and dynamic mechanical analyses showed that the encapsulation of tetracycline (5.0 wt%) did not compromise the structural integrity and compressive behavior of FlexBone, which could withstand repetitive megapascal-compressive loadings and be securely press-fitted into critical femoral defects. Dose-dependent, sustained in vitro release of tetracycline was characterized by spectroscopy and bacterial inhibition. A single dose of 40 ng BMP-2/7 or 10 ng RANKL pre-encapsulated with 50 mg FlexBone, released over 1 week, was able to induce local osteogenic differentiation of myoblast C2C12 cells and osteoclastogenesis of macrophage RAW264.7 cells, respectively. With a bonelike structural composition, useful surgical handling characteristics, and tunable biochemical microenvironment, FlexBone provides an exciting opportunity for the treatment of hard-to-heal skeletal defects with minimal systemic side effects.

SUBMITTER: Xu J

PROVIDER: S-EPMC3732452 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Sustained and localized in vitro release of BMP-2/7, RANKL, and tetracycline from FlexBone, an elastomeric osteoconductive bone substitute.

Xu Jianwen J Li Xinning X Lian Jane B JB Ayers David C DC Song Jie J

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20091001 10

We tested the hypothesis that synthetic composites containing a high percentage of osteoconductive biominerals well-integrated with a hydrophilic polymer matrix can be engineered to provide both the structural and biochemical framework of a viable synthetic bone substitute. FlexBone, an elastic hydrogel-mineral composite exhibiting excellent structural integration was prepared by crosslinking poly(2-hydroxyethyl methacrylate) hydrogel in the presence of 25 wt% nanocrystalline hydroxyapatite and ...[more]

PMID: 19350632

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Project description:Recombinant human BMP-2 (rhBMP-2) is a potent osteoinductive agent, but has been associated not only with bone formation, but also osteoclastogenesis and bone resorption. Osteoprotegerin (OPG) is a RANKL inhibitor that blocks differentiation and function of osteoclasts. We hypothesized that the combination of local BMP-2 (recombinant protein or a product of gene therapy) plus systemic OPG-Fc is more effective than BMP-2 alone in promoting bone repair. To test this hypothesis we used a mouse critical-sized femoral defect model. Col2.3eGFP (osteoblastic marker) male mice were treated with rhBMP-2 (group I), rhBMP-2 and systemic OPG (group II), rhBMP-2 and delayed administration of OPG (group III), mouse BM cells transduced with a lentiviral vector containing the BMP-2 gene (LV-BMP-2; group IV), LV-BMP-2 and systemic OPG (group V), a carrier alone (group VI) and administration of OPG alone (group VII). All bone defects treated with BMP-2 (alone or combined with OPG) healed, whereas minimal bone formation was noted in animals treated with the carrier alone or OPG alone. MicroCT analysis showed that bone volume (BV) in rhBMP-2+OPG and LV-BMP-2+OPG groups was significantly higher compared to rhBMP-2 alone (p<0.01) and LV-BMP-2 alone (p<0.001). Similar results were observed in histomorphometry, with rhBMP-2 alone defects exhibiting significantly lower bone area (B.Ar) compared to rhBMP-2+OPG defects (p<0.005) and LV-BMP-2 defects having a significantly lower B.Ar compared to all BMP-2+OPG treated groups (p≤0.01). TRAP staining demonstrated a major osteoclast response in the groups that did not receive OPG (rhBMP-2, LV-BMP-2 and sponge alone) beginning as early as 7days post-operatively. In conclusion, we demonstrated that locally delivered BMP-2 (recombinant protein or gene therapy) in combination with systemically administered OPG improved bone healing compared to BMP-2 alone in a mouse critical-sized bone defect. These data indicate that osteoclasts can diminish healing responses to BMP-2 and that RANKL inhibition may thus accentuate BMP-2 efficacy.

Dataset Information

Sustained and localized in vitro release of BMP-2/7, RANKL, and tetracycline from FlexBone, an elastomeric osteoconductive bone substitute.

Publications

Sustained and localized in vitro release of BMP-2/7, RANKL, and tetracycline from FlexBone, an elastomeric osteoconductive bone substitute.

Similar Datasets

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