Introduction: Periodontitis is a common chronic inflammatory disease that results in degradation of the supporting structures around teeth and in severe cases can lead to tooth loss. Current surgical treatments such as Guided Tissue Regeneration (GTR) are efficient at limiting the progression of the disease by controlling the inflammatory aspect of periodontitis but regeneration is not commonly achieved. Our groups have developed a tissue engineering strategy involving the utilisation of cell sheets combined with biphasic biomaterial scaffolds in order to enhance the regenerative capacity of GTR. The biphasic structures, composed of a bone and periodontal compartments, are specifically designed to recapitulate the highly organised and hierarchical architecture of the native periodontium composed of cementum, periodontal ligament, alveolar bone and gingival tissue. This paper provides an overview of the research we have performed in this area along with our latest advancements. Materials and Methods: Several generations of polycaprolactone (PCL) biphasic constructs were developed combining additive manufacturing methodologies such as Fused Deposition Modelling (FDM), solution electrospinning and Melt Electrospinning Writing (MEW). Our most recent research has resulted in the development of a fibre guiding scaffold manufactured by MEW for the bone compartment and by nanofabrication technologies for the creation aligned silk fibroin micro-channels for the periodontal compartment. Our constructs have been tested in vitro and in vivo into rodent and ovine models while testing several architectures and cell sources (gingival fibroblasts, periodontal ligament fibroblasts, and bone marrow mesenchymal stem cells). Results and Discussion: We have demonstrated that our biphasic scaffolds fulfilled the requirements for GTR; wound stabilisation, space maintenance and selective cell repopulation, and were capable of regenerating fraction or entire portion of the periodontium complex in a rodent ectopic model and in a surgically created periodontal one model. The presence of the cell sheets was also essential for the improved regeneration of the targeted organ. The incorporation of aligned channels into the biphasic scaffold design resulted in guiding the orientation of the newly formed periodontal ligament fibres. Conclusion: The development of multicompartment scaffolds for periodontal regeneration has been proven as an effective strategy when combined with cell delivery. Further to the delivery of cells, tissue guidance provided by topographical clues, is also essential and resulted in a physiologically relevant attachment of the newly formed periodontal fibres.
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