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Updated: Jul 22, 2025
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Three-dimensional Inflammatory Human Tissue Equivalents of Gingiva
Published on: April 3, 2018
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Modeling periodontal host-microbe interactions using vascularized gingival connective tissue equivalents
Hardik Makkar1, Chwee Teck Lim2,3,4, Kai Soo Tan1,5
1Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore.
Biofabrication
|July 20, 2023
Summary
Researchers developed a new model of vascularized gingival connective tissue equivalents (CTEs) to study how oral bacteria affect gum health. This model reveals how different bacteria trigger immune responses and macrophage polarization, aiding in understanding periodontitis.
Area of Science:
- Biomaterials and Tissue Engineering
- Oral Biology and Periodontology
- Immunology and Host-Microbiome Interactions
Background:
- Gingival connective tissue and its vasculature are vital for immune response to oral microbiome and systemic health.
- Existing models lack the complexity to accurately mimic vascularized gingival tissue and its interaction with oral biofilms.
- This gap hinders understanding of periodontal health and disease mechanisms.
Purpose of the Study:
- To characterize vascularized gingival connective tissue equivalents (CTEs) as a biomimetic model.
- To investigate the host-microbiome interactions between oral biofilm colonizers and gingival tissues.
- To study the innate immune response in healthy and diseased periodontal states.
Main Methods:
- Generation of bi-cellular vascularized gingival CTEs using human fibrin-based matrix, gingival fibroblasts, and microvascular endothelial cells.
- Whole-mount immunolabeling and label-free confocal reflectance microscopy for characterization.
- Exposure of CTEs to early, intermediate, and late oral biofilm colonizers, followed by cytokine/chemokine analysis, invasion assessment, monocyte migration studies, and macrophage polarization assays.
- In silico analysis of protein and transcript associations with periodontitis and vascular diseases.
Main Results:
- Vascularized gingival CTEs were successfully generated, mimicking key tissue features.
- Early colonizers did not significantly alter CTE cytokine/chemokine production, maintaining a homeostatic state.
- Intermediate and late colonizers induced connective tissue and vascular invasion, increased monocyte migration, and differential immune responses.
- Late colonizers polarized macrophages towards a pro-inflammatory M1 phenotype, while early/intermediate colonizers promoted an M2-like phenotype.
- In silico analysis revealed strong associations between investigated factors and periodontitis/vascular diseases.
Conclusions:
- Vascularized gingival CTEs offer a biomimetic in vitro platform for studying host-microbiome interactions in periodontal health and disease.
- The model effectively recapitulates key aspects of the innate immune response to oral pathogens.
- This platform may facilitate the development and evaluation of novel periodontal therapeutics.
