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Osteoinduction within BMP-2 transduced muscle tissue fragments with and without a fascia layer: implications for bone tissue engineering

Gene Therapy volume 26, pages 16–28 (2019)Cite this article

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Abstract

Bone can be engineered in vivo by implantation of gene-activated muscle tissue fragments. This expedited approach may be further improved by use of muscle tissue with attached fascia. The aim of this in vitro study was to provide an in depth comparison of the osteogenic differentiation capacity of muscle alone and muscle with fascia after BMP-2 transduction. Skeletal muscle tissue from rats was cut into pieces with and without a fascia layer on the surface. Adenoviral BMP-2 or GFP vectors were used for transduction. Osteogenic differentiation within the tissue fragments was evaluated and compared by qRT-PCR, alizarin red S staining, histomorphometry and immunohistology. Transduction efficiency and level of transgene expression were higher for muscle with fascia than muscle alone. Transduction with BMP-2 led to a significant upregulation of bone marker genes, proteins, and calcium deposition in both groups. Interestingly, histological evaluation revealed that osteoinduction did not occur within the fascia layer itself. The upregulation of bone marker genes in muscle with fascia was significantly lower after 2 weeks but similar after 4 weeks of in vitro culture in comparison to muscle alone. The fascia layer led to higher transduction efficiency and enhanced BMP-2 expression. Despite fascia’s lower capacity for osteogenic differentiation, muscle implants may benefit from the fascia layer by the improved ability to deliver BMP-2. The presented data may contribute to the development of a novel, cost-effective, single-surgery bone engineering technology and encourage the evaluation of the osteoregenerative potential of muscle with fascia in an animal model.

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Acknowledgements

This work was supported by the Friedrich-Baur-Foundation (LITE:P). BR received a fellowship from the china scholarship council (CSC) (No. 201406270144). The study sponsors did not influence the study design, the collection, analysis, and interpretation of data, the writing of the report or the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany

    Bin Ren, Volker M. Betz, Volkmar Jansson, Peter E. Müller & Oliver B. Betz

  2. Sirion Biotech GmbH, Am Klopferspitz 19, 82152, Martinsried, Germany

    Christian Thirion & Michael Salomon

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  1. Bin Ren
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  2. Volker M. Betz
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Correspondence to Bin Ren.

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CT and MS are shareholders of Sirion Biotech GmbH. Sirion Biotech GmbH produced the adenoviral vectors used in this study. All the remaining authors declare that they have no conflict of interest.

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Ren, B., Betz, V.M., Thirion, C. et al. Osteoinduction within BMP-2 transduced muscle tissue fragments with and without a fascia layer: implications for bone tissue engineering. Gene Ther 26, 16–28 (2019). https://doi.org/10.1038/s41434-018-0047-2

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  • DOI: https://doi.org/10.1038/s41434-018-0047-2

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