Bioprinting-Based PDLSC-ECM Screening for in Vivo Repair of Alveolar Bone Defect Using Cell-Laden, Injectable and Photocrosslinkable Hydrogels

Periodontitis is an inflammatory disease worldwide that may result in periodontal defect (especially alveolar bone defect) and even tooth loss. Stem-cell-based approach combined with injectable hydrogels has been proposed as a promising strategy in periodontal treatments. Stem cells fate closely depends on their extracellular matrix (ECM) characteristics. Hence, it is necessary to engineer an appropriate injectable hydrogel to deliver stem cells into the defect while serving as the ECM during healing. Therefore, stem cell-ECM interaction should be studied for better stem cell transplantation. In this study, we developed a bioprinting-based strategy to study stem cell–ECM interaction and thus screen an appropriate ECM for in vivo repair of alveolar bone defect. Periodontal ligament stem cells (PDLSCs) were encapsulated in injectable, photocrosslinkable composite hydrogels composed of gelatin methacrylate (GelMA) and poly­(ethylene glycol) dimethacrylate (PEGDA). PDLSC-laden GelMA/PEGDA hydrogels with varying composition were efficiently fabricated via a 3D bioprinting platform by controlling the volume ratio of GelMA-to-PEGDA. PDLSC behavior and fate were found to be closely related to the engineered ECM composition. The 4/1 GelMA/PEGDA composite hydrogel was selected since the best performance in osteogenic differentiation in vitro. Finally, in vivo study indicated a maximal and robust new bone formation in the defects treated with the PDLSC-laden hydrogel with optimized composition as compared to the hydrogel alone and the saline ones. The developed approach would be useful for studying cell–ECM interaction in 3D and paving the way for regeneration of functional tissue.