Artikel
Can pretreating stem cells with electrical stimulation prior to their use in bone tissue engineering improve outcomes?
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Autoren
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Liudmila Leppik
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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Kari-Leticia Klein
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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Jakob Wolf
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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Alexander Schaible
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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Santiago Bianconi
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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Karla Mychellyne Costa Oliveira
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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John Howard Barker
- Frankfurt Initiative for Regenerative Medicine, Uniklinikum Frankfurt, Goethe Universität Frankfurt, Frankfurt am Main, Germany
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Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
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Dirk Henrich
- Department of Trauma, Hand and Reconstructive Surgery, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany
| Veröffentlicht: | 23. Oktober 2023 |
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Gliederung
Text
Objectives: Electrical stimulation alone or in combination with bone tissue engineering (BTE) approaches was shown to stimulate bone healing, however the need to surgically implant, monitor, and explant the ES deviceslimit its translation into clinic. Several in vitro studies suggest that ES pro-healing effect could be due to effect on cell migration, proliferation, alignment, differentiation, and attachment to scaffold materials. In our previous study we have shown that combination of ES with BTE improves bone healing in vivo, and that exposing MSC to ES for 1 h/day for 7 days, and then stopping ES exposure, has positive osteogenic effects persisted long after ES treatment is discontinued. Based on these findings, we hypothesized that pretreating BTE constructs (MSC + Scaffold) with ES ex vivo can stimulate a sustained long-lasting increase in osteogenic activity when used to treat large bone defects. If successful, this approach will help to use the beneficial effects of the ES and avoid implantation of the device.
Methods: Femur critical size bone defects were created in 120 Sprague-Dawley rats and treated with MSC + β-TCP scaffold constructs, pre-exposed or not (control group) to ES for 7 days in 2D- or 3D-culture in vitro. Bone healing was evaluated at 1, 4, and 8 weeks post-surgery via µCT, mechanical test, histological and Immunohistochemical stainings and gene expression analysis.
Results: All animals well tolerated the treatments, bone healing continuously increased with time, however no significant difference among different treatment groups was found. All analyzed bone-healing parameters (amount of new bone, cartilage, fibrocartilage; bone mineral density, vascularization), were slightly better in defects treated with constructs pre-exposed to ES in 3D. These findings show that pre-treatment approach is unlikely to improve bone healing. As bone healing is a complex multicellular process, ES-stimulation of the MSC is not sufficient and most probably local stimulation of the bone defect area is needed.
Conclusion: Pretreating stem cells with electrical stimulation for 7 days prior to their use in bone tissue engineering is not efficient to improve bone healing outcomes. Thus, ES seems to be more effective during bone healing as indicated in further studies.
