Introduction: Despite advances in endoprosthesis fixation by implant surface alteration, the problem of aseptic implant loosening still exists. Especially in patients with revisions osseointegration and filling of gaps at the bone-implant interface is mandatory for implant survival. Simple BMP-2 immersion has been introduced previously to act as an osteoinductive coating for advanced osseointegration. However, because of the uncontrolled release kinetics and subsequent molecular action and activity of BMP-2, purely osteoinductive actions are hard to differentiate from osteoclastic BMP-actions leading to bone remodelling, which could counteract the implant fixation process and might be the reason for failed attempts to use BMP-2 for implant fixation. In this study we investigated the osteoinductive potency of BMP-2 bound to titanium surfaces by a highly controlled molecular coupling with specifically designed polymers, allowing a slow controlles release kinetics. We present the first results of two different polymers that were implanted in the tibia and femora of New Zealand White Rabbits.

Methods: In this study we designed cylindrical titanium-implants with an inner thread (Ti6-Alï·& #8220;4V, 3 mm hight x 3 mm diameter) and an electropolished outer surface that were coated with different polymers. The polymers were fixed to the surface using the photochemical method of grafting. The implants were implanted in the proximal tibia and distal femora of New Zealand White Rabbits. The anatomical locations of the implants were alternated to test their osseointegration in different quality of bone (cancellous vs. cortical bone). After 4 weeks the animals were sacrificed and DEXA-scans (Dual-energy X-ray absorptiometry), micro-CT and histological analysis were performed. ANOVA and t-test were used for statistic analysis.

Results: In high-resolution DEXA-scans we found a difference in bone mineral density (BMD) between PVBP and a control implant in the distal femora (PVBP 0,720 g/cm², control 0,661 g/cm²) and in the proximal tibia (PVBP 0,633 g/cm², control 0,431 g/cm²) with an increase of bone mineral density. In the histological investigation we found an increase of osteoblasts around the implants coated with PVBP and PVBP-Co-Acryloxysuccimid. Furthermore, the micro-CT scans showed an increase of BV/TV (bone volume/total volume) for both polymers.

Discussion: In this study we present the first results of the investigation of polymer-coated titanium-implants implanted in the proximal tibia and distal femora of New Zealand White Rabbits. The results of DEXA-scans, micro-CT and histological analysis showed an increase of osseointegration. We suggest that controlled release kinetics after coupling of these polymers with BMP-2 can additionally increase osseointegration. To get a closer look on the polymers, their characteristics in-vivo, and coupling with BMP-2 further investigations are conducted.

Introduction: New biotechnologies create opportunities for gene therapy to promote rotator cuff healing. We have previously demonstrated that genetically engineered mesenchymal stem cells (MSCs) over expressing BMP-2 and SMAD8 signaling molecule differentiate to tenocytes in vitro and in vivo. Therefore, we hypothesized that rotator cuff defect could be regenerated using genetically engineered MSCs.

Method: Nonviral methods were utilized to establish genetically engineered MSCs that co-express BMP-2 and the Smad8 signaling molecule. A previously validated animal model was utilized to examine rotator cuff healing. A 2mm x2mm full thickness defect was created in the infraspinatus tendon of 8 nude rats. A collagen-I biomembrane (TissueMend) containing 3 x 10⁶ engineered cells was sewn into the defect. An identical control procedure was repeated on the contralateral side with biomembrane containing non-engineered MSCs.

Results: 4 weeks post implantation the area of implantation was isolated and analyzed by light microscopy and histochemical staining. Analysis of the engineered implants revealed the formation of dense connective tissue with parallel-organized fibers and spindle shaped cells, unlike the control samples. Proton Double Quantum Filtered Magnetic Resonance Imaging technique of the rotator cuff tendons demonstrated an increased presence of organized collagen fibers within the engineered rotator cuff tissue when compared with either native rotator cuff or those treated with non-engineered MSCs.

Conclusion: This is the first report showing rotator cuff tendon repair using genetically engineered MSCs. Moreover these findings may have considerable importance for tendon healing and may indicate a clinical gene therapy platform to augment surgical repair.