Dentistry of the Future: Lab-Grown Teeth and the Evolution of Natural Tooth Regeneration

Researchers from King’s College London and Imperial College London have made a remarkable discovery that could potentially transform the future of dentistry: a bioengineered system capable of regrowing human teeth using stem cells and slow-release signaling technology. Published in the journal ACS Macro Letters, the revelation offers a natural substitute for traditional dental treatments ⁽³⁾ such as fillings and implants, focusing on replacing damaged or missing teeth with living, self-renewing tissue.

History of Tooth Repair

Humans have struggled with tooth decay for millennia. Archaeological evidence shows that as early as 13,000 years ago, Palaeolithic people used bitumen, plant fibers, and hair to fill cavities. By 6,500 years ago, beeswax was used as a dental filler in Slovenia. Roman scholar Pliny the Elder described similar ancient remedies in his Naturalis Historia.

Current dental fillings, typically composed of synthetic materials, are a temporary solution that can fail over time, weaken tooth structure, and cause sensitivity or further decay.

Advantages of Bioengineered Teeth

• Fully integrates with the natural jawbone

• Created from the patient’s cells — no immune rejection

• Self-repairing and longer-lasting

• Avoids complications from artificial implants

The Science Behind the Breakthrough

In the human embryo, teeth are formed by interacting stem cells⁽¹⁾, specifically epithelial and mesenchymal stem cells. These cells communicate through molecular signaling, initiating the differentiation of cell types such as ameloblasts, odontoblasts, and fibroblasts, which ultimately form enamel, dentin, and pulp, respectively.

Unlike sharks and crocodiles, humans do not retain these regenerative stem cells and cannot continuously grow new teeth. This limitation appears after the permanent dentition is established.

Hydrogels: Recreating Nature’s Developmental Environment

The new research presents a hydrogel⁽⁴⁾ matrix that mimics the original environment and replicates the conditions of early tooth development. This soft, water-absorbent scaffold allows cells to:

• Release signals incrementally (not all at once, as in past failed attempts)

• Synchronize the timing and location of signal exchange

• Differentiate into proper tooth-forming cells

This slow-release system supports organized tissue development, forming structures resembling natural teeth.

Methodology of the Study

Scientists utilized embryonic stem cells from lab mice and suspended these cells in the newly developed 3D hydrogel matrices to create a desired environment. This attempt successfully created well-organized, tooth-like structures, including dentin-pulp complexes—a key milestone in regenerative dentistry.

Challenges and Limitations

Several hurdles remain before these innovations become practical:

• The current results are derived from mouse cells, and human odontogenesis is more complex.

• Lab-grown teeth lack blood vessels and neural networks for real-life function.

• The regenerated tooth structure is in its initial developmental stages and may have incomplete structural maturity.

• The hydrogel’s biocompatibility, degradation rate, and immune response in human tissue are not fully understood. The unknown scaffold behavior of the matrix in humans should be addressed.

• Implanting and aligning lab-grown teeth within the jawbone remains technically challenging.

The Future of Regenerative Dentistry

Clinical Applications and Next Steps

Dr. Xuechen Zhang explained that the next step is to determine how to translate lab success to real patients. Two main options are being explored:

• Transplanting immature tooth cells into the jaw and allowing them to grow in place

• Growing complete teeth in the lab, then implanting them into patients

Both approaches require starting the earliest stages of tooth formation in the lab.

Advancing Customized Dental Care

This technique leads to customized dental care using a patient’s cells, enabling biologically matched tooth regeneration ⁽²⁾ that is:

• Minimally rejected

• Mimics natural form and function

• More durable than synthetic materials

Similar Global Studies

GelMA-Based Bioengineered Tooth Bud (2018, Tufts University School of Dental Medicine, Boston)
Developed tooth bud models using gelatin methacryloyl (GelMA) hydrogels, seeded with dental stem cells and later implanted in pigs. Tooth-like structures, including dentin-pulp complexes, were formed.

Injectable Microcarrier-Hydrogel Composites for Dental Stem Cells (2023, National University of Singapore)
Demonstrated that injectable hydrogel composites assist in the delivery and differentiation of dental pulp stem cells (DPSCs) for pulp regeneration.

PLGA Hydrogel Scaffolds with Dental Pulp Stem Cells (2024, University of Medical Science, Tehran, Iran)
Showed that PLGA scaffolds enhance the regenerative capacity of human DPSCs for dental tissue formation.

3D-Printed HA/PLA Scaffolds in Canine Models (2021, Tufts University School of Dental Medicine, Boston)
Used hydroxyapatite/poly (lactic acid) scaffolds in dogs, demonstrating enhanced mineralization and early dental tissue regeneration.

Hydrogel-Loaded Dental Stem Cells for Tissue Regeneration (Review)
Reviewed various hydrogels combined with dental stem cells for regenerating both soft and hard dental tissue.

Tooth Regrowth Therapy Trials for TRG-035 (2024, Kitano Hospital and Kyoto University Hospital)
Initiated the first human clinical trials for TRG-035, a drug targeting the USAG-1 protein that suppresses natural tooth development.

Expert Opinions

MedBound times connected with Dr. Rakhi Ajith and Dr. Arulvizhi M for their insights on regenerative dentistry.

A Revolution in Tooth Restoration Techniques

This research marks a major milestone toward recreating traditional dentistry with bioengineered, living teeth. Future research is inevitable, especially involving human cells, vascularized systems, and long-term trials. A future where tooth loss is no longer permanent but treatable with biologically integrated solutions is on the horizon.

The journey from ancient fillings to live, lab-grown teeth could soon be accomplished—ushering in a new era of regenerative dentistry.

References:

1. Thomson, Jess. “Lab-Grown Teeth Could Offer Alternative to Fillings and Implants, Scientists Say.” Live Science, April 25, 2025. Accessed May 9, 2025. https://www.livescience.com/health/lab-grown-teeth-could-offer-alternative-to-fillings-and-implants-scientists-say.

2. Nield, David. “Lab-Grown Teeth Are Another Step Closer to Reality, Scientists Reveal.” ScienceAlert, April 26, 2025. Accessed May 9, 2025. https://www.sciencealert.com/lab-grown-teeth-are-another-step-closer-to-reality-scientists-reveal.=

3. King's College London. “Lab-Grown Teeth Might Become an Alternative to Fillings Following Research Breakthrough.” King's College London News, April 14, 2025. Accessed May 9, 2025. https://www.kcl.ac.uk/news/lab-grown-teeth-might-become-an-alternative-to-fillings-following-research-breakthrough.Medical Xpress+2King's College London+2Reddit+2

(Input from various sources)

(Rehash/Dr. Anjaly KTK/MSM)