A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats

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A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats. / Kolk, Andreas; Tischer, Thomas; Koch, Christian; Vogt, Stephan; Haller, Bernhard; Smeets, Ralf; Kreutzer, Kilian; Plank, Christian; Bissinger, Oliver.

In: J BIOMED MATER RES A, Vol. 104, No. 10, 10.2016, p. 2441-55.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Kolk, A, Tischer, T, Koch, C, Vogt, S, Haller, B, Smeets, R, Kreutzer, K, Plank, C & Bissinger, O 2016, 'A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats', J BIOMED MATER RES A, vol. 104, no. 10, pp. 2441-55. https://doi.org/10.1002/jbm.a.35773

APA

Kolk, A., Tischer, T., Koch, C., Vogt, S., Haller, B., Smeets, R., Kreutzer, K., Plank, C., & Bissinger, O. (2016). A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats. J BIOMED MATER RES A, 104(10), 2441-55. https://doi.org/10.1002/jbm.a.35773

Vancouver

Bibtex

@article{fcc23b7e0f5f44d6889934c41659ea36,
title = "A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats",
abstract = "The osseointegration of bone implants, implant failure, and the bridging of critical-size bone defects are frequent clinical challenges. Deficiencies in endogenous bone healing can be resolved through the local administration of suitable recombinant growth factors (GFs). In preclinical models, gene-therapy-supported bone healing has proven promising for overcoming certain limitations of GFs. We report the dose-dependent bridging of critical-size mandibular bone defects (CSDs) in a rat model using a non-viral BMP-2-encoding copolymer-protected gene vector (pBMP-2) embedded in poly(d, l-lactide) (PDLLA) coatings on titanium discs that were used to cover drill holes in the mandibles of 53 male Sprague Dawley rats. After sacrificing, the mandibles were subjected to micro-computed tomography (µCT), micro-radiography, histology, and fluorescence analyses to evaluate bone regeneration. pBMP-2 in PDLLA-coated titanium implants promoted partial bridging of bone defects within 14 days and complete defect healing within 112 days when the DNA dose per implant did not exceed 2.5 µg. No bridging was observed in untreated control CSDs. Thus, the delivery of plasmid DNA coding for BMP-2 appears to be a potent method for controlled new-bone formation with an inverse dose dependency. {\textcopyright} 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2441-2455, 2016.",
keywords = "Journal Article",
author = "Andreas Kolk and Thomas Tischer and Christian Koch and Stephan Vogt and Bernhard Haller and Ralf Smeets and Kilian Kreutzer and Christian Plank and Oliver Bissinger",
note = "{\textcopyright} 2016 Wiley Periodicals, Inc.",
year = "2016",
month = oct,
doi = "10.1002/jbm.a.35773",
language = "English",
volume = "104",
pages = "2441--55",
journal = "J BIOMED MATER RES A",
issn = "1549-3296",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

RIS

TY - JOUR

T1 - A novel nonviral gene delivery tool of BMP-2 for the reconstitution of critical-size bone defects in rats

AU - Kolk, Andreas

AU - Tischer, Thomas

AU - Koch, Christian

AU - Vogt, Stephan

AU - Haller, Bernhard

AU - Smeets, Ralf

AU - Kreutzer, Kilian

AU - Plank, Christian

AU - Bissinger, Oliver

N1 - © 2016 Wiley Periodicals, Inc.

PY - 2016/10

Y1 - 2016/10

N2 - The osseointegration of bone implants, implant failure, and the bridging of critical-size bone defects are frequent clinical challenges. Deficiencies in endogenous bone healing can be resolved through the local administration of suitable recombinant growth factors (GFs). In preclinical models, gene-therapy-supported bone healing has proven promising for overcoming certain limitations of GFs. We report the dose-dependent bridging of critical-size mandibular bone defects (CSDs) in a rat model using a non-viral BMP-2-encoding copolymer-protected gene vector (pBMP-2) embedded in poly(d, l-lactide) (PDLLA) coatings on titanium discs that were used to cover drill holes in the mandibles of 53 male Sprague Dawley rats. After sacrificing, the mandibles were subjected to micro-computed tomography (µCT), micro-radiography, histology, and fluorescence analyses to evaluate bone regeneration. pBMP-2 in PDLLA-coated titanium implants promoted partial bridging of bone defects within 14 days and complete defect healing within 112 days when the DNA dose per implant did not exceed 2.5 µg. No bridging was observed in untreated control CSDs. Thus, the delivery of plasmid DNA coding for BMP-2 appears to be a potent method for controlled new-bone formation with an inverse dose dependency. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2441-2455, 2016.

AB - The osseointegration of bone implants, implant failure, and the bridging of critical-size bone defects are frequent clinical challenges. Deficiencies in endogenous bone healing can be resolved through the local administration of suitable recombinant growth factors (GFs). In preclinical models, gene-therapy-supported bone healing has proven promising for overcoming certain limitations of GFs. We report the dose-dependent bridging of critical-size mandibular bone defects (CSDs) in a rat model using a non-viral BMP-2-encoding copolymer-protected gene vector (pBMP-2) embedded in poly(d, l-lactide) (PDLLA) coatings on titanium discs that were used to cover drill holes in the mandibles of 53 male Sprague Dawley rats. After sacrificing, the mandibles were subjected to micro-computed tomography (µCT), micro-radiography, histology, and fluorescence analyses to evaluate bone regeneration. pBMP-2 in PDLLA-coated titanium implants promoted partial bridging of bone defects within 14 days and complete defect healing within 112 days when the DNA dose per implant did not exceed 2.5 µg. No bridging was observed in untreated control CSDs. Thus, the delivery of plasmid DNA coding for BMP-2 appears to be a potent method for controlled new-bone formation with an inverse dose dependency. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2441-2455, 2016.

KW - Journal Article

U2 - 10.1002/jbm.a.35773

DO - 10.1002/jbm.a.35773

M3 - SCORING: Journal article

C2 - 27176560

VL - 104

SP - 2441

EP - 2455

JO - J BIOMED MATER RES A

JF - J BIOMED MATER RES A

SN - 1549-3296

IS - 10

ER -