Humans cannot regrow permanent teeth once they are lost, but for the first time in history, that biological limitation is being challenged in clinical trials. A Japanese research team began testing an antibody drug in 2024 that stimulates dormant tooth buds, while parallel efforts in stem cell biology and bioengineering are producing functional tooth-like structures in animal models. None of these approaches are available to the public yet, and the gap between a mouse growing an extra tooth and a person regrowing a molar is enormous. Still, the science has moved well past speculation.
Why Humans Cannot Regrow Teeth but Alligators Can
Most mammals, including humans, get exactly two sets of teeth: baby teeth and permanent teeth. Once a permanent tooth is gone, the dental lamina, the ribbon of tissue that originally gave rise to it, has already been used up and largely dissolved. Reptiles play by different rules. Alligators cycle through roughly 80 teeth over a lifetime. Researchers have mapped a population of dormant stem cells sitting in a bulge at the end of the alligator’s dental lamina. These cells stay quiet until a tooth falls out or is pulled, at which point they activate and generate a replacement.1PubMed Central. Specialized stem cell niche enables repetitive renewal of alligator teeth Leopard geckos operate similarly, relying on a stable pool of epithelial stem cells in their dental lamina to form new teeth on demand.2PubMed Central. Tooth Removal in the Leopard Gecko and the de novo Formation of Replacement Teeth
Even within mammals, there are hints that the regenerative machinery hasn’t completely vanished. Mouse incisors grow continuously throughout the animal’s life, powered by epithelial and mesenchymal stem cells tucked away at the base of each incisor.3PubMed Central. On the cutting edge of organ renewal: Identification, regulation, and evolution of incisor stem cells More detailed gene-mapping work has identified distinct stem cell pools in these incisors: one that renews the enamel-producing cells and another that maintains the tissue anchoring the tooth in the jaw.4eLife. Resolving stem and progenitor cells in the adult mouse incisor through gene co-expression analysis Humans lost this continuous-growth capability, but the signaling pathways that drive it still exist in our genome, silenced but not deleted. That is the opening that tooth regeneration researchers are trying to exploit.
The Anti-USAG-1 Antibody, the Closest Thing to a Tooth Regrowth Drug
The most advanced approach to regrowing whole teeth in humans targets a protein called USAG-1. In normal development, USAG-1 acts as a brake on the signaling pathways that tell cells to form teeth. When researchers knocked out the gene for USAG-1 in mice, the animals developed extra teeth because the molecular brakes were removed and dormant tooth buds that would normally be reabsorbed were allowed to develop instead.5PubMed. Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse The extra teeth formed from rudimentary tooth germs that exist in the jaw but are programmed to self-destruct during normal development.
Building on that discovery, a team at Kyoto University developed an antibody that blocks USAG-1 specifically in a way that boosts tooth-forming signals without broadly disrupting other organs. The key was finding an antibody that interfered with USAG-1’s binding to bone morphogenetic proteins (the growth signals for tooth development) while leaving its interaction with another receptor relatively untouched.6PubMed Central. Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling This selectivity matters because the pathways USAG-1 regulates are active in many tissues, and broadly blocking them could cause unwanted bone or tissue growth elsewhere.
The humanized version of this antibody, designated TRG035, is now in clinical testing.7PubMed. Imaging biomarkers as surrogate endpoints for clinical trials on permanent tooth regeneration in congenital tooth agenesis A phase I trial was initiated at Kyoto University Hospital in 2024, enrolling adults to evaluate safety and tolerability. The initial target population is people with congenital tooth agenesis, a condition in which some permanent teeth never develop because the tooth buds are present but fail to mature. If the drug works as intended, it would coax those dormant buds into completing development. Phase II studies focused on congenital tooth agenesis are anticipated by 2026, with broader trials and potential commercialization projected for around 2030.8PubMed Central. USAG‐1 and Regenerative Dentistry, Therapeutic Implications and Future Directions: Review of the Literature
There is an important caveat here that often gets lost in media coverage. The antibody works by waking up tooth buds that already exist but failed to develop. It does not create new tooth buds from scratch. For people who lost teeth due to injury or decay in adulthood, the original tooth buds are long gone, and this particular drug would not help. The initial clinical application is narrow: congenital tooth agenesis, which affects roughly 0.1% of the population. Whether the same approach could eventually be expanded to acquired tooth loss remains an open and much harder question.
Growing Teeth from Stem Cells
A separate line of research skips the antibody route entirely and instead tries to build teeth from cellular raw materials. Dental pulp stem cells, harvested from the soft tissue inside teeth (often extracted wisdom teeth or children’s baby teeth), have properties that make them attractive for regenerative work: they multiply readily, can differentiate into several tissue types, and survive long-term cryopreservation.9PubMed Central. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives Early clinical work has shown that transplanting stem cells from baby teeth into damaged permanent teeth can regenerate three-dimensional pulp tissue complete with blood vessels and sensory nerves, with follow-up showing stability over two years.10MedNEXT Journal of Medical and Health Sciences. Dental stem cells and tissue regeneration in odontology: a brief systematic review
But regenerating pulp inside an existing tooth is a different challenge from growing an entire new tooth. For whole-tooth bioengineering, researchers have tried recombining the two types of progenitor cells that build natural teeth, epithelial and mesenchymal cells, seeded onto scaffolds that mimic the architecture of a developing tooth bud. One approach used cells from pig tooth buds combined with human endothelial cells encapsulated in a hydrogel scaffold designed to replicate the layered structure of a natural tooth bud.11PubMed Central. Developing a biomimetic tooth bud model Another group used decellularized scaffolds made from actual tooth bud tissue, stripping away the original cells but preserving the three-dimensional protein framework, then repopulating them with new cells. The resulting constructs formed dentin, cementum, and periodontal ligament tissue that closely resembled natural tooth structures under the microscope.12PubMed Central. In vivo bioengineered tooth formation using decellularized tooth bud extracellular matrix scaffolds
The most dramatic proof-of-concept came from a Japanese group that transplanted bioengineered tooth germs into the jaws of mice. The resulting teeth erupted, developed correct internal structure, achieved functional hardness, and responded to pain and mechanical stress the way normal teeth do.13PubMed Central. Fully functional bioengineered tooth replacement as an organ replacement therapy A follow-up study showed that transplanting a complete bioengineered “tooth unit,” including the tooth, periodontal ligament, and surrounding bone, could integrate with the host jaw through normal bone remodeling and support chewing.14PubMed Central. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy These are mouse-scale achievements, and scaling them to human-sized teeth introduces a cascade of engineering problems. But they demonstrate that the biological recipe for a functional tooth can be followed outside of natural development.
Repairing Damaged Enamel Without Regrowing the Tooth
While whole-tooth regeneration remains a future prospect, a more modest goal is already being pursued: repairing enamel that has been damaged by decay or cracking, without drilling and filling. Enamel is the hardest substance in the human body but cannot repair itself once lost, because the cells that produce it are destroyed when teeth finish forming. Self-assembling peptides represent one attempt to cheat this limitation. These are short protein fragments that, when applied to a damaged area, spontaneously organize into a scaffold that attracts calcium and phosphate ions from saliva, promoting the formation of hydroxyapatite crystals, the same mineral that makes up natural enamel.15PubMed Central. Biomimetic Enamel Regeneration Using Self-Assembling Peptide P(11)-4
The results are mixed. One lab study found that a specific self-assembling peptide could seal natural tooth cracks with crystals whose hardness and composition matched natural enamel after 14 days of treatment.16PubMed Central. Morphological Characterizations and Mineralized Repair of Natural Tooth Cracks Via Self-Assembling Peptide Hydrogels But another study testing the same class of peptide on artificial enamel cavities found it could not significantly slow cavity progression or visually mask the damage, with a low-viscosity resin performing better on both counts.17PubMed. Effects of Self-Assembling Peptide P11-4, Fluorides, and Caries Infiltration on Artificial Enamel Caries Lesions in vitro The gap likely reflects differences in the severity and type of damage being repaired: sealing a crack in otherwise intact enamel is a different task from rebuilding a cavity. For now, self-assembling peptides are more useful for very early, superficial damage than for the kind of cavities that currently require fillings.
Another lab approach uses low-power laser light to trigger dentin repair from inside the tooth. Researchers showed that shining a specific wavelength of low-power laser onto exposed dentin activated a latent growth factor (TGF-β1) that was already present in the tissue, which then prompted resident stem cells to produce new dentin. This worked in rat teeth, producing measurable new dentin formation, and the effect was specifically dependent on the growth factor pathway, confirmed by the fact that it failed in genetically modified mice lacking the relevant receptor.18PubMed Central. Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration The appeal of this approach is that it uses the body’s own repair cells and growth signals rather than introducing outside materials. The limitation is that it works for dentin, the layer beneath enamel, and cannot regenerate enamel itself.
Why Growing a Whole Tooth Is So Much Harder Than It Sounds
A tooth is not a simple structure. It is an organ with at least four distinct hard and soft tissue types (enamel, dentin, cementum, and pulp), each produced by different cell lineages, all arranged in precise spatial relationships. On top of that, a tooth needs to be anchored in bone by a periodontal ligament whose fibers run perpendicular to the root surface, connected to a blood supply that keeps the pulp alive, and wired into the nervous system for sensation. Regenerating the three components of the periodontal attachment, cementum, ligament fibers, and bone, in their correct orientation remains one of the biggest unsolved challenges in dental tissue engineering.19PubMed Central. Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells
Then there is the problem of tooth shape. Human teeth are not interchangeable: an incisor, a canine, and a molar have completely different crown shapes, root numbers, and cusp patterns. During natural development, the shape of each tooth is determined by a cascade of molecular signals that differ depending on where in the jaw the tooth is forming. Subtle changes in the timing and intensity of these signals produce the difference between a pointed canine and a flat-surfaced molar.20PubMed Central. Morphoregulation of teeth: modulating the number, size, shape and differentiation by tuning Bmp activity Replicating this patterning artificially, so that a bioengineered tooth grows into the right shape for the right position, is a control problem that nobody has solved at human scale. In mouse experiments, bioengineered teeth have erupted and functioned, but a mouse molar is tiny and anatomically simpler than a human one.
Stiffness of the scaffold also matters in unexpected ways. Recent work on dental pulp stem cells showed that the mechanical properties of the three-dimensional material they grow in dramatically influence what kind of tissue they produce. By varying stiffness across different zones of a single scaffold, researchers were able to steer stem cells toward producing dentin in one region and pulp-like tissue in another, mimicking the natural layered organization of a real tooth.21PubMed Central. Three-dimensional matrix stiffness-based stem cell soil: Tri-phase biomechanical structure promoted human dental pulp stem cells to achieve pulpodentin regeneration This kind of fine-tuning is encouraging for the field, but it also illustrates how many variables need to be controlled simultaneously to get a recognizable tooth rather than a disorganized clump of dental tissues.
The Age Problem
Most people who need new teeth are not children. They are adults in their 50s, 60s, and beyond, and this creates a biological headwind for regenerative strategies that depend on stem cells. Dental stem cells age along with the rest of the body. Their ability to proliferate, differentiate, and respond to growth signals declines over time due to a combination of disrupted signaling pathways, metabolic changes, and accumulated modifications to how their genes are read. These age-related impairments diminish the regenerative potential of dental stem cells and limit how useful they might be in older patients who need them most.22PubMed Central. Decoding Dental Stem Cell Aging: Mechanisms, Therapeutic Strategies, and Beyond
This is one reason why some researchers are interested in banking dental stem cells early in life, harvesting them from extracted baby teeth or wisdom teeth in young adulthood, cryopreserving them, and potentially using them decades later when regenerative treatments become available. Dental pulp stem cells survive cryopreservation well.9PubMed Central. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives Whether cells frozen at age 20 will still perform optimally when thawed and deployed at age 70 is a question that won’t be answered for a long time, but the logic is sound: younger cells have better regenerative capacity, and if you know the technology is coming, preserving them is a reasonable hedge.
The anti-USAG-1 antibody approach partially sidesteps the aging problem by working with dormant tooth buds rather than requiring exogenous stem cells. But even that approach depends on a local tissue environment capable of supporting tooth development, and the jawbone of a 70-year-old is not the same as that of a teenager. Bone density, blood supply, and the surrounding soft tissue all change with age and with conditions like diabetes or osteoporosis, making the host environment less hospitable for any regenerative process.
What Supernumerary Teeth Tell Us
Some people already grow more teeth than the standard 32. Supernumerary teeth, extra teeth beyond the normal count, occur in a small percentage of the population and are sometimes associated with genetic conditions such as cleidocranial dysostosis and Gardner’s syndrome. These extra teeth form because the developmental program that normally shuts down after producing the correct number of teeth fails to fully shut off. In a sense, people with supernumerary teeth are naturally doing a version of what the anti-USAG-1 antibody is trying to achieve pharmacologically: allowing additional tooth buds to develop rather than be reabsorbed.
The existence of supernumerary teeth is actually encouraging for the regeneration field, because it proves that human jaws retain latent capacity to produce teeth beyond the two standard sets. The extra teeth are often malformed, poorly positioned, or problematic enough to require extraction, which highlights the difficulty of controlling where and how new teeth form. But they demonstrate that the fundamental cellular machinery for tooth production can still be activated in humans, given the right (or, in the case of these genetic conditions, the unintentionally altered) signaling environment.
How Dental Implants Compare
For people losing teeth today, titanium dental implants remain the gold standard. They are durable, well-studied, and can last decades with proper maintenance. But they have real limitations that a regenerated biological tooth would not share. Implants do not have a periodontal ligament, so they connect rigidly to bone rather than through the slight cushion that natural teeth have. This makes them less responsive to biting forces and can lead to progressive bone loss around the implant over time. They cannot sense temperature or pressure the way a natural tooth does. They are susceptible to peri-implantitis, a destructive inflammatory condition at the implant-bone interface that is surprisingly common in long-term follow-up. And they need adequate bone volume for placement, which means patients with significant jawbone loss often require bone grafting procedures first.
A regenerated tooth, if the technology ever matures, would theoretically solve all of these problems. It would have its own periodontal ligament, its own nerve supply for sensation, and the capacity to remodel alongside the surrounding bone naturally. Mouse studies have already demonstrated that bioengineered tooth units can achieve periodontal ligament function and respond to pain stimuli after transplantation.14PubMed Central. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy The practical question is not whether a biological tooth would be better than a titanium one; it’s whether the technology can be made reliable, affordable, and scalable enough to compete.
Realistic Timelines and What to Watch For
The most aggressive public timeline comes from the Japanese group behind the USAG-1 antibody, who have projected potential commercialization around 2030 pending regulatory approval.8PubMed Central. USAG‐1 and Regenerative Dentistry, Therapeutic Implications and Future Directions: Review of the Literature That timeline, if met, would apply only to congenital tooth agenesis, not to routine tooth replacement for cavities or trauma. For the broader population of adults missing teeth due to decay, gum disease, or injury, the honest answer is that clinically available tooth regeneration is likely decades away, not years. Whole-tooth bioengineering has not yet been demonstrated in any animal larger than a mouse. Scaling up from mouse to human involves not just bigger scaffolds and more cells, but solving the patterning, vascularization, and integration problems described above at a size that makes them orders of magnitude harder.
If you are a patient making decisions today, none of this changes your options yet. Dental implants, bridges, and dentures remain the practical solutions for missing teeth. But the pipeline is real and worth watching. The phase I safety trial results for TRG035 should begin emerging within the next few years and will be the first concrete signal of whether pharmacological tooth regeneration in humans is possible or remains confined to laboratory animals. For the stem cell and bioengineering approaches, the milestones to look for are successful demonstrations in larger animal models, particularly pigs or non-human primates, with functional teeth that persist long-term. Until those milestones are met, the field remains firmly in the territory of promising but unproven.