Abstract
Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration—culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch.
Highlights
Periodontal disease and periodontium defects, including irreversible destructions of alveolar bone, periodontal ligament (PDL) and other tissues surrounding and supporting tooth structure, eventually lead to tooth loss [1,2]
The regeneration process involves a series of interactions between cells comprising the complex periodontium tissue structure, i.e., alveolar bone, root cementum and PDL
In PDL, an important population of cells has been identified as stem cells which have a multipotency, and the cells are recognized to play essential roles in the regeneration process of the periodontal complex tissues, regulating osseous remodeling and ligament formation by differentiation into either cementoblasts or osteoblasts depending on the needs and conditions [6,7]
Summary
Periodontal disease (periodontitis) and periodontium defects, including irreversible destructions of alveolar bone, periodontal ligament (PDL) and other tissues surrounding and supporting tooth structure, eventually lead to tooth loss [1,2]. The regeneration process involves a series of interactions between cells comprising the complex periodontium tissue structure, i.e., alveolar bone, root cementum and PDL. PDL plays a central role in the regeneration process of periodontal pocket. In PDL, an important population of cells has been identified as stem cells which have a multipotency, and the cells are recognized to play essential roles in the regeneration process of the periodontal complex tissues, regulating osseous remodeling and ligament formation by differentiation into either cementoblasts or osteoblasts depending on the needs and conditions [6,7]. Many studies have demonstrated the PDL primary cells and the isolated stem cell populations showed osteoblastic differentiation in vitro in response to common osteogenic culture conditions [6,8,9]
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