Objectives: The innate healing potential of periodontium has emerged as a new focus for regenerative therapies. Consequently, cell homing is appealing because it relies on attraction of the patient’s own stem cells. Stromal cell-derived factor-1 alpha (SDF-1α) plays a major role in this process. The aim of this study was to develop a construct for periodontal regeneration based on cell homing with SDF-1α, and to evaluate its effect on early and late wound healing in a periodontal defect model. Methods: For the preparation of the construct, gelatin sponge loaded with recombinant human SDF-1α was used. The release kinetics of SDF-1α were studied in vitro. A transwell migration model was used to test the in vitro homing capability of the SDF-1α construct for rat bone marrow stromal cells (BMSCs). Subsequently, constructs were tested for efficacy in a validated rat periodontal model. In 48 athymic nude rats, intrabony periodontal defects were created unilaterally and implanted with either (i) SDF-1α-loaded gelatin sponge, (ii) gelatin sponge, or (iii) left empty as a control for evaluation periods of 1 and 6 weeks (n=8). Evaluation consisted of descriptive histology, histomorphometry (epithelial downgrowth, inflammation, functional ligament length, new bone area, new bone height) and micro-CT (volume newly formed bone). In vivo recruitment of rat BMSCs to the defect site was tested immunohistochemically, whereby green fluorescent protein (GFP)-transgenic rat BMSCs were injected into the tail vein of the rats. GFP-positive cells in the defect site were quantified in situ by flow cytometry in 12 nude athymic rats using the same experimental set-up. All measurements were subjected to statistical analysis with ANOVA and differences were considered significant at p Results: The in vitro release experiment showed limited release of SDF-1α (picogram quantities following nanogram loading). The transwell migration model proved the site-homing capability of the SDF-1α construct in vitro for the rat BMSCs. At 1 week post-implantation, the histological tissue response in the defect was similar for all groups, with epithelial downgrowth, inflammation (30%), minor bone formation and no periodontal ligament formation. At 6 weeks post-implantation, SDF-1α constructs showed more newly formed bone area and height (0.4mm versus 0.2mm and 0.13mm versus 0.8mm), longer relative functional ligament (0.3mm versus 0.2mm) and less inflammation (6% versus 12%) compared to gelatin controls. However, the differences between the SDF-1α group and empty defects were not significant, except for newly formed bone height (14% versus 7%). Epithelial downgrowth was comparable for all groups at 1 and 6 weeks. The micro-CT data supported the histomorphometrical findings. The volume of the newly formed bone for SDF-1α constructs was significantly higher than for both gelatin and empty controls after 6 weeks (18% versus 10% and 8%). At 1 and 6 weeks post-implantation, no GFP-positive BMSCs were detected in the defect. Conclusion: The SDF-1α construct significantly improved periodontal wound healing at 6 weeks in terms of bone regeneration. In view of suboptimal release kinetics of SDF-1α from the gelatin sponge, alternative carriers need to be explored to maximise the potential for bone regenerative procedures via cell homing.

Gliederung: - Chirurgisches Wunddebridement - Sequestrotomie - Präparation des Weichgewebelagers - Plastischer, spannungsfreier, speicheldichter Wundverschluss Materialliste: Chirurgisches Grundset: - Skalpell - Präparierschere - Pinzette - Nahtmaterial