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J Gene Med. 2017 Sep;19(9-10). doi: 10.1002/jgm.2972. Epub 2017 Sep 22.

BMP-2 gene activated muscle tissue fragments for osteochondral defect regeneration in the rabbit knee.

Author information

1
University Center of Orthopaedics and Traumatology and Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany.
2
Department of Orthopaedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.
3
Department of Orthopaedics and Sportsorthopaedics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
4
Sirion Biotech GmbH, Martinsried, Germany.
5
DFG-Center for Regenerative Therapies Dresden, Dresden, Germany.

Abstract

BACKGROUND:

Previously published data indicate that BMP-2 gene activated muscle tissue grafts can repair large bone defects in rats. This innovative abbreviated ex vivo gene therapy is appealing because it does not require elaborative and time-consuming extraction and expansion of cells. Hence, in the present study, we evaluated the potential of this expedited tissue engineering approach for regenerating osteochondral defects in rabbits.

METHODS:

Autologous muscle tissue grafts from female White New Zealand rabbits were directly transduced with an adenoviral BMP-2 vector or remained unmodified. Osteochondral defects in the medial condyle of rabbit knees were treated with either BMP-2 activated muscle tissue implants or unmodified muscle tissue or remained empty. After 13 weeks, repair of osteochondral defects was examined by biomechanical indentation testing and by histology/imunohistochemistry applying an extended O'Driscoll scoring system and histomorphometry.

RESULTS:

Biomechanical investigations revealed a trend towards slightly improved mechanical properties of the group receiving BMP-2 activated muscle tissue compared to unmodified muscle treatment and empty defect controls. However, a statistically significant difference was noted only between BMP-2 muscle and unmodified muscle treatment. Also, histological evaluation resulted in slightly higher histological scores and improved collagen I/II ratio without statistical significance in the BMP-2 treatment group. Histomorphometry indicated enhanced repair of subchondral bone after treatment with BMP-2 muscle, with a significantly larger bone area compared to untreated defects.

CONCLUSIONS:

Gene activated muscle tissue grafts showed potential for osteochondral defect repair. There is room for improvement via the use of appropriate growth factor combinations.

KEYWORDS:

BMP-2; biomechanical indentation testing; cartilage repair; gene therapy; muscle tissue; osteochondral defect

PMID:
28744947
DOI:
10.1002/jgm.2972
[Indexed for MEDLINE]

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