Gene therapy for the regeneration of bone

Evans, Christopher H.

doi:10.1016/j.injury.2011.03.032

Cited by 60 publications

(57 citation statements)

References 72 publications

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“…In a second step we performed a quantitative analysis of newly formed bone within the defect area. Bone volume was expressed in mm 3 per defect.…”

Section: Imagingmentioning

confidence: 99%

“…Despite encouraging results in clinical routine therapy costs still are high and the local use of highly increased BMP concentrations raises safety concerns [2]. An alternative strategy is the delivery of BMP transgenes instead of recombinant growth factors in order to generate a local sustained release of host-cell produced, highly bioactive growth factors [3][4][5][6]. Recent experimental data showed a synergistic effect of BMP2 and BMP7 therapeutic gene co-delivery [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Kaipel

Schützenberger

Hofmann

et al. 2014

International Orthopaedics (SICOT)

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PURPOSE: Treatment of large segmental bone defects still is a challenge in clinical routine.Application of Gene-activated matrices (GAMs) based on fibrin, BMP 2/7 plasmids and nonviral transfection reagents (cationic polymers) could be an innovative treatment strategy to overcome this problem.The aim of this study was to determine the therapeutic efficacy of fibrin GAMs with or without additional transfection reagents for bone morphogenic protein (BMP)2 and BMP7 plasmid co-delivery in a rat femur non-union model. METHODS:In this experimental study a critical size femoral defect was created in 27 rats. At 4 weeks after the surgery animals were separated into 4 groups and underwent a second operation. Fibrin clots containing BMP2 and BMP7 plasmids with and without cationic polymer were implanted into the femoral defect. Fibrin clots containing recombinant human (rh) BMP2 served as positive and clots without supplement as negative controls.RESULTS: At 8 weeks animals which received GAMs containing the cationic polymer and BMP 2/7 plasmids showed decreased bone volume compared to animals treated with GAMs and BMP2/7 only. Application of BMP2 and BMP7 plasmids in fibrin GAMs without cationic polymer lead to variable results. Animals which received rhBMP 2 protein showed increased bone volume and osseous unions were achieved in 2 out of 6 animals.2 CONCLUSIONS: Cationic polymers decrease therapeutic efficiency of fibrin GAM based BMP2/7 plasmid co-delivery in bone regeneration. Non-viral gene transfer of BMP2/7 plasmids needs alternative promoters (e.g. by sonoporation, electroporation) to promise beneficial clinical effects.

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“…In a second step we performed a quantitative analysis of newly formed bone within the defect area. Bone volume was expressed in mm 3 per defect.…”

Section: Imagingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Kaipel

Schützenberger

Hofmann

et al. 2014

International Orthopaedics (SICOT)

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“…16 In addition, gene therapy concepts with good prospects are required for future treatment options based on intracellular manipulation. 17 Due to the great potential for nanoparticles in the applications indicated here, these topics are discussed against the background of bone cells and tissue.…”

Section: Applications Of Nanoparticles In Bonementioning

confidence: 99%

Nanoparticles and their potential for application in bone

Tautzenberger¹,

Kovtun²,

Ignatius³

2012

IJN

163

137

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Abstract:Biomaterials are commonly applied in regenerative therapy and tissue engineering in bone, and have been substantially refined in recent years. Thereby, research approaches focus more and more on nanoparticles, which have great potential for a variety of applications. Generally, nanoparticles interact distinctively with bone cells and tissue, depending on their composition, size, and shape. Therefore, detailed analyses of nanoparticle effects on cellular functions have been performed to select the most suitable candidates for supporting bone regeneration. This review will highlight potential nanoparticle applications in bone, focusing on cell labeling as well as drug and gene delivery. Labeling, eg, of mesenchymal stem cells, which display exceptional regenerative potential, makes monitoring and evaluation of cell therapy approaches possible. By including bioactive molecules in nanoparticles, locally and temporally controlled support of tissue regeneration is feasible, eg, to directly influence osteoblast differentiation or excessive osteoclast behavior. In addition, the delivery of genetic material with nanoparticulate carriers offers the possibility of overcoming certain disadvantages of standard protein delivery approaches, such as aggregation in the bloodstream during systemic therapy. Moreover, nanoparticles are already clinically applied in cancer treatment. Thus, corresponding efforts could lead to new therapeutic strategies to improve bone regeneration or to treat bone disorders.

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“…They promote enhanced therapeutic outcome by providing controlled release of bioactive molecules, such as growth factors or anticancer drugs (Allen and Cullis, 2004). In addition, gene therapy concepts with good prospects are required for future treatment options based on intracellular manipulation (Evans, 2011).…”

Section: Biomaterials As Supportmentioning

confidence: 99%