3D human cell culture models in periodontal research: A scoping review

Despite the increasing use of 3D in vitro models in periodontal research, there is currently no comprehensive synthesis explicitly mapping how effectively these models translate structural achievements into functional biological fidelity. Thus, this scoping review aims to map the existing literature while critically evaluating the biological complexity and translational value of current human 3D in vitro periodontal models.

PubMed, Cochrane Library, and Web of Science databases were searched to identify relevant original studies detailing the development and application of human 3D in vitro models in periodontal research.

A substantial increase in publications since 2018 was observed, reflecting a growing interest in physiologically relevant in vitro systems. However, our analysis highlights a critical gap between structural innovation and biological fidelity. Most studies (76.2%) employ single-cell-type culture systems, predominantly utilizing periodontal ligament stem cells. Methodologically, conventional fabrication techniques remain dominant (84.8%), particularly solid scaffolds and hydrogels, whereas scaffold-free approaches are less frequent. Only 23.8% of the models incorporate multiple cell types, and the integration of immune components is mostly absent. Furthermore, complex dysbiotic microbial communities, which play a central role in periodontal pathogenesis, are rarely included.

While the structural biofabrication of periodontal models has significantly advanced, their functional biological relevance remains restricted. To better recapitulate disease mechanisms and enhance clinical predictivity, future models must shift toward integrating multicellular microenvironments, immune system components, and dynamic host-microbiome interactions.