Interactive fibroblast-keratinocyte co-cultures: an in vivo-like test platform for dental implant-based soft tissue integration.

For clinicians, soft connective tissue integration (STI), one of the critical issues for dental implant success, is usually tested using the fibroblasts monolayer regime. Therefore, we aimed at an extension of this regime by employing interactive gingival fibroblast-keratinocyte cocultures (CCs) as an in vivo-like test platform. In the extended regime, 13 STI-relevant genes were analyzed in response to five different titanium implant biomaterial surfaces. The genes quantitated by real-time polymerase chain reaction were categorized as pro supportive or contra supportive, that is, nonsupportive for cell growth on an engineered surface. Monocultures had higher levels of contra supportive gene expression, but the fibroblast-keratinocyte CC had two out of five of the titanium surfaces with more pro supportive gene expression than contra supportive gene expression. We defined this change from contra supportive gene expression to pro supportive gene expression by developing the "relative supportive difference" index. Hence, interactive CCs exhibit valuable supportive effects on the expression of STI-relevant genes, possibly via physiological cell-to-cell-interactions. Our results render interactive gingival CCs suitable as a test platform for dental implant-related STI under more in vivo-like conditions.