A living tooth in cross-section — mineral matter, a luminous vascular pulp, and a faint computational design-space converging.
Dental Pulp Regeneration · NUS Dentistry

Dental pulp regeneration · matter, tissue, innovation

Regenerating the Living Tooth.

The pulp is the living core of the tooth. It allows the tooth to sense injury, defend the dentin–pulp complex, form dentin in response to its environment and sustain root development in immature teeth.

Endodontic treatment controls infection, seals the canal and preserves teeth in function. Regenerative research asks a further question: can living, vascularized and dentin-forming tissue be engineered within the root?

Matter for Vitality is a research programme connecting bioactive materials, pulp tissue engineering and scientific innovation. It studies how materials shape the wound environment, how tissue organizes within root anatomy, and how new cellular and computational approaches expand what can be constructed, predicted and experimentally validated.

02  /  The programme

Matter. Tissue. Innovation.

Restoring pulp vitality brings together three connected dimensions: the material interface, the tissue that must form within the canal, and the innovations that expand how both can be constructed, predicted and tested.

Matter

Bioactive materials seal the exposure and shape the chemistry, surface and ion environment encountered by the injured pulp.

Tissue

Scaffolds, cells, matrix cues and vascular ingrowth must organize within the confined anatomy of the root to form viable pulp-like tissue.

Innovation

Tissue engineering, renewable experimental cell sources and computational material design expand what can be constructed, predicted, refined and experimentally validated.

Together, they frame pulp regeneration as a programme connecting material behaviour, tissue formation and scientific invention.

03  /  Matter · The biological interface

From filling to fulfilling.

A pulp-capping material seals the exposure and creates the first chemical, physical and biological conditions encountered by the injured pulp.

Cross-section of vital pulp therapy: a calcium-silicate cement caps the exposed pulp, a new dentin bridge forms beneath it, and the living vascular pulp responds.

At the pulp-capping interface, calcium-silicate cement seals the exposure while its chemistry, surface and released ions shape the local tissue response.

At the chairside, a pulp-capping material must handle predictably, set within a clinically useful time, seal the exposure, remain stable and remain visible radiographically.

At the tissue interface, the same material establishes a local chemistry, releases ions and presents a surface that influences cell survival, inflammatory response and mineralized tissue formation.

Clinical and biological requirements must operate together. Chemistry, alkalinity, ion release, microstructure and surface properties shape how the injured pulp encounters treatment and how repair progresses toward organized mineralized tissue formation.

At the wound interface, material performance becomes biological consequence.

Evidence · Material formulation and biological response
04  /  Tissue · Engineering pulp within the root

Tissue must organize across the canal.

Pulp regeneration depends on building a vascularized tissue system within the confined anatomy of the root.

Longitudinal section of a tooth root whose canal has been repopulated with living, vascularized pulp-like tissue connecting from the apex to the pulp chamber, lined by a forming odontoblast layer.

A conceptual longitudinal view of vascularized pulp-like tissue extending from the apical region toward the chamber, with an odontoblast-like interface forming along dentin.

In experimental models, injectable scaffolds carrying dental stem cells have supported vascularized pulp-like tissue and tubular dentin formation within full-length human root canals.

This tissue must develop across a narrow, elongated anatomy supplied from the apical region. Survival depends on vascular ingrowth, spatial organization and integration with the surrounding dentin.

The translational challenge is to reproduce this organization, integration and function within the tooth under clinically realistic conditions.

Tissue organization

Across the full canal

Vascularized pulp-like tissue and tubular dentin across full-length root-canal models.

Cell source

Toward odontoblast-like cells

A renewable experimental cell source capable of forming pulp-like tissue and tubular dentin.

Pulp tissue engineering

Complementary questions in tissue organization and cell source.

These approaches were investigated in distinct experimental models.

Explore the pulp-regeneration research

Tissue in formation

How tissue forms through the canal.

Tissue formation begins when a scaffold, cells, matrix cues and vascular ingrowth organize within the root as a connected biological system.

A conceptual sequence showing how matter, cells, vascular ingrowth and a dentin-forming interface contribute to pulp-like tissue organization.

Scroll ↓  follow tissue formation through the canal

00

The prepared canal

A confined anatomical space prepared to receive a tissue-engineering construct.
Design constraintCreating conditions for tissue survival across the full canal length.
Conceptual starting state
Cleaned, empty root canal Root canal filled with an injectable scaffold Scaffold seeded with stem cells Root canal with vascularized pulp-like tissue Regenerated canal with new tubular dentin
Experimental evidence
Rosa et al. · J Dent Res 2013

Full-length human root-canal model

Human premolar roots containing SHED delivered in hydrogels developed vascularized pulp-like tissue and tubular dentin in vivo.

Why it matters

The model demonstrated that tissue organization, vascularization and a dentin-forming interface could develop across the complete canal anatomy.

View J Dent Res 2013
Evidence linked to each stage
Root canal with vascularized pulp-like tissue

Regeneration rebuilds the biological conditions required for pulp-like tissue to survive, vascularize and interact with dentin.

Conceptual sequence based on experimental tissue-engineering models; it does not represent an established clinical procedure.

05  /  Innovation · From intuition to design

Design turns complexity into testable decisions.

Regeneration depends on interacting choices: cells, scaffolds, matrix cues, material composition, timing, vascular organization and biological response.

Biomaterials on the left feed a luminous computational design network that flows rightward and becomes the living vascular pulp inside a molar crown.

Biological and computational innovation expand the regenerative toolkit — from renewable odontoblast-like cell sources to target-driven material formulations validated at the bench.

Tissue engineering brings cells, scaffolds and matrix cues together to study how viable pulp-like tissue can form within root anatomy.

New cellular approaches expand the biological resources available to this work. Reprogramming dental pulp stem cells into induced pluripotent stem cells established a renewable experimental route toward odontoblast-like cells while preserving tissue engineering as the broader regenerative strategy.

Computational design approaches the material problem from the target backwards. Models map how formulation variables influence setting, strength, radiopacity, alkalinity, ion release and biological response, then identify recipes predicted to balance these properties. This allows clinical, physicochemical and biological trade-offs to be considered together.

Each prediction returns to the bench for physicochemical and biological validation.

Computational material design
1 · Map
Link formulation variables to material behaviour.
2 · Predict
Estimate performance across the formulation space.
3 · Prescribe
Select recipes that match target properties.
4 · Validate
Test predicted behaviour at the bench.
The design cycle closes when predicted behaviour is confirmed experimentally.
Explore Biomaterials & AI
06  /  Reading the field · How evidence is built

The models shape the questions.

Scientific progress depends on knowing what each model makes visible—and what it may distort.

One piece of living pulp biology at the centre, seen through three overlapping circular lenses: one faithful, one distorted, one partial.
Faithful Distorted Partial

The same pulp biology viewed through three experimental lenses: faithful, distorted and partial.

Models and assays determine which part of the biology becomes visible. A cell model may simplify the tissue it represents; a biomaterial may alter the chemistry or optics of an assay; and a comparison may appear meaningful until its controls and limitations are examined.

This work asks which models suit each question, which comparisons are valid, which readouts capture function, and where material interference or experimental artefacts may distort interpretation.

A field matures when it can distinguish a biological effect from an artefact introduced by the model, assay or comparison used to measure it.
Methodological guidance · Dental Materials 2025
07  /  Published work

Evidence across the programme.

A published trajectory across matter, tissue, innovation and evidence.

2013
J Dent Res 92(11)
Tissue

Dental Pulp Tissue Engineering in Full-Length Human Root Canals

What changed — Demonstrated vascularized pulp-like tissue and tubular dentin formation across full-length human root-canal models.

Rosa V, Zhang Z, Grande RHM, Nör JE. · J Dent Res 2013;92(11):970–975.

View Paper
2015
J Appl Oral Sci
Matter

Bioactivity, Physical and Chemical Properties of MTA Mixed with Propylene Glycol

What changed — Showed how a formulation change could improve flowability and calcium release without automatically improving cellular bioactivity.

Natu VP, Dubey N, Loke GCL, Tan TS, Ng WH, Yong CW, Cao T, Rosa V. · J Appl Oral Sci 2015.

View Paper
2018
J Dent Res 97(1)
Tissue · Cell source

Functional Odontoblastic-Like Cells Derived from Human iPSCs

What changed — Established a renewable experimental route to odontoblast-like cells capable of forming pulp-like tissue and tubular dentin in a subcutaneous dentin-disc model.

Xie H, Dubey N, Shim W, Ramachandra CJA, Min KS, Cao T, Rosa V. · J Dent Res 2018;97(1):77–83.

View Paper
2020
J Biomed Mater Res B
Tissue · Innovation

Taguchi’s Methods to Optimize the Properties and Bioactivity of 3D-Printed Polycaprolactone/Mineral Trioxide Aggregate Scaffolds

What changed — Used Taguchi design to identify which scaffold variables controlled pH, degradation, porosity and mechanical behaviour, then confirmed the predictions experimentally.

Bhargav A, Min KS, Lu WF, Fuh JYH, Rosa V. · J Biomed Mater Res B Appl Biomater. 2020;108B:629–637.

View Paper
2022
Int Endod J
Reading the field

A Critical Analysis of Research Methods and Biological Experimental Models to Study Pulp Regeneration

What changed — Mapped how cell, tissue and animal models shape the questions, strengths and limitations of pulp-regeneration research.

Rosa V, Sriram G, McDonald N, Cavalcanti BN. · Int Endod J 2022.

View Paper
2022
Dent Clin N Am 66
Tissue

Regenerating the Dental Pulp — Scaffold Materials and Approaches

What changed — Connected cell-based, cell-homing and scaffold strategies to the biological requirements of pulp tissue formation.

Soares DG, Rosa V. · Dent Clin N Am 2022;66:643–657.

View Paper
2023
J Dent Res 102(13)
Innovation · Computational design

Designing Calcium Silicate Cements with On-Demand Properties for Precision Endodontics

What changed — Demonstrated target-driven, multi-property prediction of calcium-silicate cement recipes followed by experimental validation.

Cahyanto A, Rath P, Teo TX, Tong SS, Malhotra R, Cavalcanti BN, Lim LZ, Min KS, Ho D, Lu WF, Rosa V. · J Dent Res 2023;102(13):1425–1433.

View Paper
2025
Dental Materials 41
Reading the field

Guidance for Evaluating Biomaterials’ Properties and Biological Potential for Dental Pulp Tissue Engineering and Regeneration Research

What changed — Connected material characterization, biological models, functional outcomes and reporting quality within a unified evaluation framework.

Rosa V, Cavalcanti BN, Nör JE, Tezvergil-Mutluay A, Silikas N, Bottino MC, Kishen A, Soares DG, Franca CM, Cooper PR, Duncan HF, Ferracane JL, Watts DC. · Dental Materials 2025;41:248–264.

View Paper
2025
Dental Materials 41(12)
Innovation · Predictive modelling

pH Prediction in Commercial and Experimental Calcium Silicate Cements via Material Informatics

What changed — Predicted long-term alkalinity from early pH measurements and specimen surface area, then validated the model across commercial and experimental calcium-silicate cements.

Sabino CF, Grymak A, Silikas N, Rosa V. · Dental Materials. 2025;41(12):1600–1608.

View Paper