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Background <p>Peri-implant health depends on the complex interactions between the dental implant, surrounding soft/hard tissues and the oral microbial environment. However, existing 2D and monoculture models fail to replicate this complexity, limiting their clinical relevance. Therefore, this study aimed to develop a clinically relevant 3D in vitro model that integrates oral soft tissue, hard tissue and a titanium implant in a 3D setup to accurately replicate the peri-implant environment. In addition, the model was designed to integrate bacterial biofilms, in order to mimic incipient peri-implant infections.</p> Methods <p>As a hard tissue component, osteoblast-covered HA/TCP scaffold structures were developed and merged with peri-implant mucosa, resulting in a 3D in vitro peri-implant bone-mucosa composite model. The composite model was then cultivated for 2, 7 and 14 days. At each time point, histological analysis, live/dead staining and collagen immunofluorescence staining were performed to assess its structural integrity, osteoblast viability and bone ECM characteristics. To demonstrate proof-of-concept for suitability in simulating implant infection, an oral multispecies biofilm was integrated on top of the implant in the peri-implant bone-mucosa model.</p> Results <p>Cell viability and osteoblastic phenotype were maintained throughout the study period. Microscopic and histological analyses confirmed a homogenous structure, with a stratified epithelium overlying collagen-embedded human gingival fibroblasts closely connected to the underlying scaffold structure interspersed with bone cells. Combined with a living multispecies biofilm, this model represents several essential components observed in peri-implant interaction.</p> Conclusions <p>By combining oral soft tissue, hard tissue and a titanium implant in a 3D setup, this model represents the first and most complex model for evaluating innovative implant materials and novel treatment strategies as well as studying the development of peri-implant diseases. Incorporating different biofilms could enhance the model’s clinical relevance, enabling the study of pro-inflammatory responses to bacterial infections in a setting that includes both soft and hard tissue.</p>

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Establishment of a three-dimensional in vitro peri-implant bone-mucosa composite model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Behnaz Malekahmadi,
  • Marjan Kheirmand-Parizi ,
  • Carina Mikolai,
  • Andreas Winkel ,
  • Muhammad Imran Rahim,
  • Katharina Doll-Nikutta,
  • Andreas Kampmann ,
  • Nils-Claudius Gellrich ,
  • Dagmar Wirth ,
  • Henning Menzel ,
  • Meike Stiesch

摘要

Background

Peri-implant health depends on the complex interactions between the dental implant, surrounding soft/hard tissues and the oral microbial environment. However, existing 2D and monoculture models fail to replicate this complexity, limiting their clinical relevance. Therefore, this study aimed to develop a clinically relevant 3D in vitro model that integrates oral soft tissue, hard tissue and a titanium implant in a 3D setup to accurately replicate the peri-implant environment. In addition, the model was designed to integrate bacterial biofilms, in order to mimic incipient peri-implant infections.

Methods

As a hard tissue component, osteoblast-covered HA/TCP scaffold structures were developed and merged with peri-implant mucosa, resulting in a 3D in vitro peri-implant bone-mucosa composite model. The composite model was then cultivated for 2, 7 and 14 days. At each time point, histological analysis, live/dead staining and collagen immunofluorescence staining were performed to assess its structural integrity, osteoblast viability and bone ECM characteristics. To demonstrate proof-of-concept for suitability in simulating implant infection, an oral multispecies biofilm was integrated on top of the implant in the peri-implant bone-mucosa model.

Results

Cell viability and osteoblastic phenotype were maintained throughout the study period. Microscopic and histological analyses confirmed a homogenous structure, with a stratified epithelium overlying collagen-embedded human gingival fibroblasts closely connected to the underlying scaffold structure interspersed with bone cells. Combined with a living multispecies biofilm, this model represents several essential components observed in peri-implant interaction.

Conclusions

By combining oral soft tissue, hard tissue and a titanium implant in a 3D setup, this model represents the first and most complex model for evaluating innovative implant materials and novel treatment strategies as well as studying the development of peri-implant diseases. Incorporating different biofilms could enhance the model’s clinical relevance, enabling the study of pro-inflammatory responses to bacterial infections in a setting that includes both soft and hard tissue.