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Combining electrical stimulation and tissue engineering to treat large bone defects in a rat model.

ABSTRACT: Bone Tissue engineering (BTE) has recently been introduced as an alternative to conventional treatments for large non-healing bone defects. BTE approaches mimic autologous bone grafts, by combining cells, scaffold, and growth factors, and have the added benefit of being able to manipulate these constituents to optimize healing. Electrical stimulation (ES) has long been used to successfully treat non-healing fractures and has recently been shown to stimulate bone cells to migrate, proliferate, align, differentiate, and adhere to bio compatible scaffolds, all cell behaviors that could improve BTE treatment outcomes. With the above in mind we performed in vitro experiments and demonstrated that exposing Mesenchymal Stem Cells (MSC)?+?scaffold to ES for 3 weeks resulted in significant increases in osteogenic differentiation. Then in in vivo experiments, for the first time, we demonstrated that exposing BTE treated rat femur large defects to ES for 8 weeks, caused improved healing, as indicated by increased bone formation, strength, vessel density, and osteogenic gene expression. Our results demonstrate that ES significantly increases osteogenic differentiation in vitro and that this effect is translated into improved healing in vivo. These findings support the use of ES to help BTE treatments achieve their full therapeutic potential.

SUBMITTER: Leppik L

PROVIDER: S-EPMC5910383 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Combining electrical stimulation and tissue engineering to treat large bone defects in a rat model.

Leppik Liudmila L Zhihua Han H Mobini Sahba S Thottakkattumana Parameswaran Vishnu V Eischen-Loges Maria M Slavici Andrei A Helbing Judith J Pindur Lukas L Oliveira Karla M C KMC Bhavsar Mit B MB Hudak Lukasz L Henrich Dirk D Barker John H JH

Scientific reports 20180420 1

Bone Tissue engineering (BTE) has recently been introduced as an alternative to conventional treatments for large non-healing bone defects. BTE approaches mimic autologous bone grafts, by combining cells, scaffold, and growth factors, and have the added benefit of being able to manipulate these constituents to optimize healing. Electrical stimulation (ES) has long been used to successfully treat non-healing fractures and has recently been shown to stimulate bone cells to migrate, proliferate, al ...[more]

PMID: 29679025

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Project description:BackgroundBone tissue engineering is not widely used in clinical treatment. Two main reasons hide behind this: (1) the seed cells are difficult to obtain and (2) the process of tissue engineering bone construction is too complex and its efficiency is still relatively low. It is foreseeable that in the near future, the problem of seed cell sources could be solved completely in tissue engineering bone repair. As for the complex process and low efficiency of tissue engineering bone construction, usually two strategies would be considered: (1) the construction strategy based on injectable bone tissue and (2) the construction strategy based on osteogenic cell sheets. However, the application of injectable bone tissue engineering (iBTE) strategy and osteogenic cell sheet strategy is limited and they could hardly be used directly in repairing defects of large segmental bone, especially load-bearing bone.MethodsIn this study, we built an osteogenic micro-tissue with simple construction but with a certain structure and composition. Based on this, we established a new iBTE repair strategy-osteogenic micro-tissue in situ repair strategy, mainly targeting at solving the problem of large segmental bone defect. The steps are as follows: (1) Build the biodegradable three-dimensional scaffold based on the size of the defect site with 3D printing rapid prototyping technology. (2) Implant the three-dimensional scaffold into the defect site. This scaffold is considered as the "steel framework" that could provide both mechanical support and space for bone tissue growth. (3) Inject the osteogenic micro-tissue (i.e., the "cell-extracellular matrix" complex), which could be considered as "concrete," into the three-dimensional scaffold, to promote the bone tissue regeneration in situ. Meanwhile, the digested cells were injected as the compared group in this experiment. After 3 months, the effect of in situ bone defect repair of osteogenic micro-tissue and digested cells was compared.ResultsIt is confirmed that osteogenic micro-tissue could achieve a higher efficiency on cell usage and has a better repair effect than the digested cells.ConclusionsOsteogenic micro-tissue repairing strategy would be a more promising clinical strategy to solve the problem of large segmental bone defect.

Dataset Information

Combining electrical stimulation and tissue engineering to treat large bone defects in a rat model.

Publications

Combining electrical stimulation and tissue engineering to treat large bone defects in a rat model.

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