3D-Bioprinted Human Periodontal/Osteoblastic Microfluidic Tissue-on-A-Chip System and Evaluation of Model Drug Interactions

While periodontal (PD) disease is among principal causes of tooth loss worldwide, regulation of concomitant soft and mineralized PD tissues, and PD pathogenesis have not been completely clarified yet. Besides, relevant pre-clinical models and in vitro platforms have limitations in accurately simulating human physiology. A periodontium-on-a-chip, emulating PD ligament-alveolar bone (PDL-AB) biointerface has not been developed to date. In this study, we have harnessed three-dimensional bioprinting (3DP) technology for developing such a system for the first time. PDL was modelled by using gelatin methacryloyl (Gel-MA) bioink for bioprinting human periodontal ligament fibroblasts. On the side, AB was modelled by using a composite bioink comprised of Gel-MA and hydroxyapatite-magnetic iron oxide nanoparticles (Gel-MA/HAp-MNPs) for bioprinting human osteoblasts. MNPs were incorporated to bring magnetic properties to the mineralized layer for use in prospective orthodontic mechanotransduction studies. The 3DP parameters of the composite microtissue were optimized; the physical, chemical, rheological, mechanical, and thermal properties of the constructs were assessed. Finally, preliminary evaluation of the model drug tetracycline interactions was performed. Thus, the effects of the tetracyclines on PDL-AB have clinical significance for treating PD diseases. This periodontium-on-a-chip model represents a reproducible in vitro platform for studying processes of healthy and diseased human PDL.