Complex in vitro model systems to understand the biointerfaces of dental implants

This narrative review aims to provide an overview of in vitro models to evaluate new materials or surface functionalities in dental implant research. The focus lies on concepts and models rather than specific materials or cell types.

Literature searches were conducted using PubMed, Web of Science, and google scholar. Major focus was on in vitro studies using mammalian cells that evaluated different implant materials with respect to soft tissue adhesion or osseointegration. Keywords were combinations of in vitro models, dental materials, dental implantology, cells, cell material interactions, or biointerfaces. A total of 147 articles are included in this review.

The majority of studies report on first-line in vitro evaluations with static 2D cell cultures on cylindrical discs of the material of interest. One step further, more advanced 2D models incorporated multiple cell types or studied signaling pathways and mechanisms. Only few publications reported on truly 3D models. A new category of dynamic culture models or integrated implant-on-a-chip systems is arising. We conclude that more research is needed to understand clinical observations on the cellular level and that standardized protocols are needed to evaluate new materials.

To accommodate patient-specific requirements, new technologies for surface treatments and functionalizations are required. Thereby, the portfolio of standard titanium or zirconia-based dental implants will undoubtedly be complemented with novel materials. In the scope of reducing, refining and replacing animal studies, preceding in vitro evaluations must be more predictive to account for the increasing demand for material evaluations and medical device regulations.