gms | German Medical Science

Objectives: Large bone defects, secondary to open fractures, non-unions, infections and tumors are a major challenge in Orthopedics and Trauma Surgery. Current treatments use autologous and allogenous bone to repair these defects and while effective are associated with several problems and complications. Tissue engineering (TE) and electrical stimulation (ES) techniques have been used separately both in pre-clinical and clinical settings with promising results. In this study we tested the hypothesis, that combining TE and ES will create a synergy that results in better outcomes than is achieved with either treatment individually. We tested this hypothesis in a rat femur critical size defect (CSD) treated with adipose tissue derived mesenchymal stem cells (AT-MSC), calcium phosphate scaffold material (ß-TCP) and ES.

Methods: Rat femur CSDs treated with AT-MSC + Beta-TCP scaffold material and exposed to ES with a custom-made implantable ES device. Quality of bone healing was assessed 1 and 8 weeks post surgery in 3 groups (Control = ß-TCP alone; Sham = ß-TCP + AT-MSC + deactivated ES device; Experimental = ES + ß-TCP + AT-MSC) of 40 animals by histological characterization, gene-expression analysis and 3-point breaking test.

Results and Conclusion: One week after surgery endochondral ossification centers were observed only in the ES treated defects. At 8 weeks histology revealed newly formed bone (all groups), hypertrophied cartilage (ES group) and fibrous tissue (sham and control groups). Analysis of osteogenic marker gene expression in the defect area, using qRT-PCR, showed that ES caused an increase in RunX2 and Osteopontin expression as early as 1 week after surgery and Osterix, TGF-ß1, Calmodulin expression at 8 weeks after surgery. Evaluation of mechanical properties of newly formed bone in the defect at 8 weeks showed that the sham group presented lower elastic modulus and higher deformation compared to the control and ES groups. However sham and control curves showed longer strain zone after reaching the elastic limit and before fracture.

Based on our histology and gene expression analysis data, ES appears to enhance MSC osteogenic differentiation and consequently bone healing in our rat femur model. These findings suggest that ES enhances bone healing in the TE treatment approach we tested, and therefore could be used to improve bone TE based treatments in the clinical setting.