Stem cell Janus patch for periodontal regeneration

Abstract Periodontitis places a substantial burden on healthcare worldwide. Due to the complexity of the periodontium, regenerative periodontal therapy in healing periodontal tissue damage caused by periodontitis has long been difficult using traditional tissue engineering techniques. The current clinical treatment, guided tissue regeneration (GTR), has shown limitations in reconstructing an osteogenic microenvironment. Here, we designed a stem cell-containing patch (stem cell “Janus” patch; SCJP) to acclimatize stem cells in the osteogenic and odontogenic microenvironment for periodontal regeneration. The SCJP promoted periodontal regeneration within its functional layer, while its barrier layer blocked gingival epithelial cells (GECs) invasion. Specifically, embedded dental pulp stem cells (DPSCs) in the functional layer facilitated the regeneration of dentin, cementum and alveolar bone, all of which orchestrated complete periodontal structure regeneration. We characterized the biophysical properties of the SCJP barrier layer, which has a compact structure and appreciable resistance to mechanical stress, suggesting the patch may be effective in preventing epithelium invasion. Successful ectopic mineralization and further osteogenic and odontogenic differentiation in mouse, rat and swine periodontal defect models further validated the patch’s potential in accelerating periodontal tissue regeneration. Our study describes a safe and effective stem cell-base strategy for a therapeutic that not only realizes periodontal repair but also protects the restoring periodontium from epithelial cell invasion.