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Guided Endodontics: Three-Dimensional Planning and Template-Aided Preparation of Endodontic Access Cavities

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Microenvironmental Challenges in Regenerative Endodontic Procedures: Disinfection, Tissue Engineering and Future

Sahng G Kim¹, Prasanna Neelakantan^2,3,4,5,6, Maobin Yang⁷

¹Division of Endodontics, Columbia University College of Dental Medicine, New York City, New York, USA.

International Endodontic Journal

|March 10, 2026

Summary

True regeneration of the pulp-dentine complex via regenerative endodontic procedures (REPs) is hindered by disinfection and regeneration microenvironment limitations. Novel strategies integrating infection control with advanced tissue engineering are needed for true biological regeneration.

Keywords:

biofilm microenvironment regenerative endodontic procedures revitalisation scaffold stem cells of the apical papilla tissue engineering

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Area of Science:

Biomaterials Science
Regenerative Medicine
Endodontics

Background:

Regenerative endodontic procedures (REPs) aim for true pulp-dentine complex regeneration, but clinical outcomes often reflect tissue repair.
Current REPs face challenges in optimizing the microenvironment for both disinfection and regeneration stages.

Purpose of the Study:

To review the limitations of the current regenerative microenvironment in REPs.
To discuss emerging strategies for integrating infection control with tissue engineering in REPs.

Main Methods:

Literature review focusing on disinfection and regeneration challenges in REPs.
Analysis of stem cell interactions, biomaterial limitations, and microenvironmental factors.
Exploration of novel antimicrobial and tissue engineering approaches.

Main Results:

Endodontic biofilms resist disinfection, impacting stem cell odontogenic potential.
Immune cells (macrophages) modulate stem cell regenerative capacity.
Scaffolds and microenvironmental conditions (hypoxia, nutrient restriction) limit tissue organization and vascularization.

Conclusions:

Current REPs protocols are insufficient for true regeneration due to microenvironmental limitations.
Advanced strategies involving multifunctional biomaterials are crucial for overcoming these challenges.
Novel antimicrobial approaches and sophisticated tissue engineering designs are essential for achieving true biological regeneration of the pulp-dentine complex.