The End of 'Drill and Fill': How Biomimetic Science and Regrowth Drugs Are Transforming Dentistry

For over a century, the fundamental philosophy of dentistry has been subtractive. When a tooth is damaged by decay or trauma, the standard protocol is to drill away the disease, remove compromised tissue, and replace it with inert synthetic materials like amalgam, porcelain, or titanium. It is a mechanical solution to a biological problem, often trapping patients in a cycle of increasingly invasive procedures—from fillings to crowns, root canals, and eventually extractions. But a profound paradigm shift is currently sweeping through dental science. Driven by advances in molecular biology and adhesive technologies, the era of "drill and fill" is giving way to the regenerative era.[1][5][6]

The most dramatic evidence of this shift is unfolding in clinical trials across Japan, where researchers are testing the world's first tooth-regrowing drug. Developed by Toregem Biopharma, a biotech startup spun out of Kyoto University, the experimental intravenous drug aims to do what was long considered scientifically impossible: stimulate the human body to grow a brand-new, natural tooth from scratch. Following successful animal trials in mice and ferrets, and initial Phase 1 safety trials in adult men in late 2024, the treatment has advanced to a critical new phase.[2][4]

The drug, currently known as TRG035, works by targeting a specific protein called Uterine Sensitization Associated Gene-1, or USAG-1. In human biology, USAG-1 acts as a natural brake on tooth development. While humans are born with the cellular blueprints for primary (baby) and permanent (adult) teeth, we also possess dormant "third" tooth buds. Under normal circumstances, the USAG-1 protein suppresses these dormant buds, preventing humans from growing continuous sets of teeth like sharks or alligators do.[3][4]

Toregem's breakthrough was developing a monoclonal antibody that temporarily inhibits the USAG-1 protein. By neutralizing this biological brake, the drug allows Bone Morphogenetic Proteins (BMPs)—signaling molecules that regulate bone and organ development—to freely stimulate those dormant tooth buds. In laboratory settings, a single dose of the antibody was enough to trigger the formation of a complete, structurally sound tooth.[2][3][4]

The immediate focus of the ongoing 2025 and 2026 clinical trials is not the general public, but children aged two to six who suffer from congenital tooth agenesis (anodontia). This genetic condition affects roughly 0.1% of the global population, leaving children entirely without permanent tooth buds. For these patients, the absence of teeth causes severe functional difficulties with chewing and speech, alongside significant psychological and developmental challenges. Currently, their only options are poorly fitting pediatric dentures or waiting until adulthood for invasive titanium implants.[1][3][4]

If TRG035 proves safe and effective in these pediatric trials, Toregem Biopharma hopes to eventually expand the treatment to adults who have lost teeth due to severe cavities, gum disease, or trauma. The prospect of replacing a lost molar with a biologically identical, lab-stimulated natural tooth would fundamentally disrupt the $5 billion global dental implant market, offering a seamless biological cure rather than a prosthetic patch.[1][2]

However, clinical skeptics caution that regrowing teeth in adults presents massive biological hurdles. Dr. Mary MacDougall, a leading dental researcher at the University of British Columbia, has noted that while young children possess abundant dental epithelial cells necessary for tooth formation, adults who have been missing teeth for years may lack the cellular foundation required for the drug to work.[2][7]

Furthermore, targeting the therapy remains a complex pharmacological challenge. Because the drug is administered systemically, researchers must ensure that inhibiting USAG-1 only triggers tooth growth in the specific, desired empty socket, rather than causing unwanted supernumerary teeth to erupt elsewhere in the jaw or disrupting bone development in other parts of the body.[2][7]

While systemic tooth regeneration remains in the trial phase, the underlying philosophy of working with the body's biology—rather than against it—is already transforming everyday dental clinics through a movement known as "biomimetic dentistry." Derived from "bio" (life) and "mimetic" (to mimic), this approach abandons the aggressive mechanical retention techniques of the past in favor of preserving maximum natural tooth structure.[5][6]

Traditional dentistry often relies on geometry to keep restorations in place. To fit a conventional crown, a dentist must grind down the tooth into a small peg, frequently removing up to 70% of healthy, structurally sound enamel and dentin just to create room for the porcelain cap. This aggressive reduction traumatizes the living nerve inside the tooth, significantly increasing the likelihood that the patient will eventually need a root canal.[1][5]

Biomimetic dentists view the natural tooth as a masterpiece of engineering that cannot be perfectly replicated by any synthetic material. Instead of grinding down a compromised tooth for a crown, they use advanced adhesive protocols to bond composite resins or ceramic onlays directly to the remaining healthy structure. Techniques like Immediate Dentin Sealing (IDS) protect the freshly exposed inner tooth layer from bacterial invasion and sensitivity, while Deep Margin Elevation (DME) allows dentists to restore deep cavities without cutting away healthy bone.[5][6]

The goal of these biomimetic restorations is to replicate the exact biomechanics of a natural tooth. Natural teeth are not rigid; they flex microscopically under the immense pressures of chewing, thanks to the shock-absorbing properties of the dentino-enamel junction. Traditional stiff crowns disrupt this flexibility, often leading to catastrophic root fractures. Biomimetic materials are layered specifically to mimic this natural flexibility, absorbing stress and preventing the tooth from cracking down the middle.[5][6]

This biological approach is also reshaping preventative home care. For decades, the standard for cavity prevention has been fluoride, which hardens existing enamel. Today, biomimetic oral care products are increasingly utilizing nano-hydroxyapatite—the exact calcium-phosphate mineral that makes up 97% of human tooth enamel. Rather than just hardening the surface, these biomimetic toothpastes actively remineralize the tooth, filling in microscopic scratches and reversing early decay before a cavity can fully form.[1]

Ultimately, the shift toward biomimetic and regenerative dentistry represents an ethical and economic realignment in oral healthcare. By prioritizing right-sized, evidence-informed care over aggressive overtreatment, the industry is moving toward a model where patients keep their natural teeth longer, experience fewer complications, and avoid the painful, expensive cascade of structural dental failure. Whether through advanced adhesives that mimic natural enamel or groundbreaking antibodies that regrow missing teeth entirely, the future of dentistry is undeniably biological.[1][5][6]