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Reconceptualizing gingival keratinization: from epithelial autonomy to artificial intelligence-driven therapeutic
Delfin Lovelina Francis1, Saravanan Sampoornam Pape Reddy2, Pradeep Kumar Yadalam3
1Department of Public Health Dentistry, Saveetha Dental College & Hospitals, Saveetha University, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, 600077, India.
Odontology
|September 12, 2025
Summary
Gingival keratinization, crucial for periodontal health, is now understood to be primarily regulated by epithelial factors, not connective tissue (CT). This research highlights epithelial-intrinsic mechanisms for better soft tissue regeneration therapies.
Area of Science:
- Periodontal Biology
- Epithelial Biology
- Tissue Regeneration
Background:
- Gingival keratinization is essential for maintaining periodontal health.
- Traditionally, connective tissue (CT) was believed to drive this process.
- Recent evidence suggests epithelial-intrinsic factors play a dominant role.
Purpose of the Study:
- To critically review the role of connective tissue (CT) in gingival keratinization.
- To evaluate recent hypotheses emphasizing keratinocyte autonomy.
- To shift the paradigm from a CT-driven to an epithelial-mediated model of keratinization.
Main Methods:
- Comprehensive literature review of animal models, human studies, and genetic research.
- Analysis of studies on heterotopic gingival grafts and growth factor signaling.
- Utilized artificial intelligence for predictive modeling of gingival keratinization.
Main Results:
- Gingival keratinization is not solely dictated by connective tissue (CT).
- Epithelial factors, including signaling molecules, growth factors (TGF-β, KGF), and keratinocyte genetic regulation, are dominant.
- Keratinocyte differentiation can occur independently of CT signals.
Conclusions:
- The paradigm of gingival keratinization is shifting from a CT-driven to an epithelial-mediated process.
- Epithelial-intrinsic factors are the primary regulators of keratinization.
- Modulating epithelial factors is crucial for effective periodontal regenerative therapies and soft tissue regeneration.
