AUGMENTATION OF MASSIVE IMPLANT FIXATION USING MESENCHYMAL STEM CELLS

Abstract

Introduction: The survival of massive endoprosthesis replacements is not as successful as conventional joint replacements. The main cause of failure of these implants is aseptic loosening. Bone in-growth onto the implant collar on the shaft of the prosthesis adjacent to the transaction site has been correlated with a decrease in radiolucent lines adjacent to the intramedullary stem and reduced implant loosening. We propose that bone contact and in-growth to the collar may be further enhanced with tissue engineering techniques. The hypothesis of this study was that autologous mesenchymal stem cells (MSCs) suspended within fibrin glue and sprayed onto hydroxyapatite (HA)-coated collars of massive prosthesis will augment bone growth and contact to the implant in an ovine model.

Materials and Methods: MSCs were isolated and expanded in vitro from the iliac crest of six adult sheep. Pre-implantation, 2 x 106 autologous MSCS were suspended in thrombin. During surgery, this mixture was combined with fibrinogen and sprayed onto the proximal and distal HA-coated collars of tibial midshaft prostheses using pressurized air. The implants were cemented into the right hind limb of twelve sheep, six of which received MSCs. Radiographs were taken at 2, 4 and 6 months and bone area within defined regions quantified using image analysis software. After six months, specimens were retrieved and processed for undecalcified histology. Transverse thin sections were prepared through the centre of each collar. Image analysis was used to quantify bone area and contact. Mann Whitney U tests were used for comparative statistical analysis, where p< 0.05 was classified as significant.

Results: Anterior-posterior (AP) radiographs taken at 2, 4, and 6 months showed that animals treated with MSCs produced more bone adjacent to the shaft of the implant. Analysis of bone area on both AP and medio-lateral (ML) radiographs taken after sacrifice showed that stem cell-treated implants encouraged significantly more total bone around the implants at 6 months than the control group (171.94 ± 29.04 mm2, and 87.51 ± 9.81 mm2 bone area, respectively, p = 0.016). Analysis of histological sections shows a significant increase in bone area around midshafts treated with MSCs, compared to the implant controls (53.99 ± 10.64 mm2, and 21.07 ± 7.34 mm2, respectively; p = 0.020). The average surface area contact between the midshaft and bone was almost doubled in the MSC-implant group (19.83 ± 8.73 % contact) than in the control group (8.667 ± 8.667 %, p = 0.196). In the MSC group bone was seen deep within the grooves of the HA coated collar whilst a fibrous soft tissue layer separated the newly formed bone in the control group.

Conclusion: Bone contact and in-growth to massive endoprostheses was significantly improved by spraying the implant with autologous MSCs suspended in fibrin glue. Enhanced fixation using stem cells may help prevent aseptic loosening in these massive implants.