Chapter 29: Emerging Technologies — CPP-ACP, Bioactive Glasses, and the Future¶

The remineralization landscape is evolving rapidly. Beyond fluoride and nano-hydroxyapatite, several technologies are emerging that may define the next generation of dental care. Some are already available; others remain in the research pipeline. All of them share a common philosophy: work with the natural chemistry of teeth rather than just killing bacteria and hoping for the best.

Let me walk you through the most promising developments.

CPP-ACP: Milk Proteins for Your Teeth¶

One of the more elegant remineralization technologies emerged from an unexpected source: milk.¹ Specifically, a protein fragment derived from casein—the primary protein in dairy.

The Science¶

Casein phosphopeptide (CPP) is a portion of the casein protein that has a remarkable property: it can bind and stabilize calcium and phosphate ions in solution, preventing them from precipitating while keeping them bioavailable.

Amorphous calcium phosphate (ACP) is a non-crystalline form of calcium phosphate—the raw material for enamel, but in a form that remains available for remineralization rather than immediately crystallizing.

Together, CPP-ACP creates a delivery system that:

Carries high concentrations of calcium and phosphate
Binds to dental plaque, tooth surfaces, and soft tissues
Creates a local reservoir of remineralization ions
Releases calcium and phosphate when pH drops (exactly when needed)

It's like having a smart mineral supplement that deposits its payload precisely when and where demineralization threatens.

The Products¶

MI Paste (GC America) is the primary commercial CPP-ACP product, developed from research at the University of Melbourne. It's available in:

Standard formulation (CPP-ACP alone)
MI Paste Plus (CPP-ACP + 900 ppm fluoride)

The combination product is particularly interesting: fluoride for acid resistance plus CPP-ACP for mineral delivery. They appear to be synergistic.

The Evidence¶

Multiple clinical trials support CPP-ACP:

White spot lesion remineralization: A 2008 study in Caries Research showed significantly better remineralization of white spots in orthodontic patients using MI Paste compared to placebo.²

Caries prevention: Mixed results. Some studies show benefit; others don't. The evidence isn't as strong as for fluoride, but the mechanism is sound.

Sensitivity: Good evidence for reducing dentin hypersensitivity.

Erosion protection: Some evidence that CPP-ACP buffers against erosive acid exposure.

Who Benefits Most¶

CPP-ACP is particularly valuable for:

Orthodontic patients (high white spot risk)
Post-bleaching sensitivity
Early enamel lesions visible as white spots
High-risk patients wanting additional protection
Those who want a remineralization boost beyond toothpaste

Limitations¶

Milk allergy: CPP is derived from casein, making MI Paste unsuitable for those with milk protein allergies.

Cost: MI Paste is significantly more expensive than toothpaste, typically $20+ per tube.

Application method: It's meant to be applied with a finger or tray and left on teeth—not a toothpaste, but a topical treatment.

Bioactive Glasses: Controlled Mineral Release¶

In 1969, Larry Hench at the University of Florida was trying to develop materials for implants when he accidentally created a glass that bonded to bone.³ That discovery led to Bioglass, and eventually to bioactive glasses for dental use.

The Chemistry¶

Bioactive glasses are silica-based materials with specific compositions (typically including sodium, calcium, and phosphate oxides) that react with aqueous environments in predictable ways:

Ion exchange: Glass surface releases sodium and calcium ions while taking up hydrogen
pH rise: Local alkalinity increases, potentially buffering acid
Silica gel formation: A hydrated silica-rich layer forms
Calcium phosphate precipitation: Hydroxyapatite-like material deposits on the glass surface

The result is a material that "actively" participates in mineralization rather than being an inert filler.

Dental Products¶

NovaMin (now owned by GSK) is a bioactive glass formulation used in:

Sensodyne Repair & Protect (in some markets)
Various professional desensitizing treatments

BioMinF is a newer bioactive glass that incorporates fluoride into the glass structure, providing slow-release fluoride in addition to calcium and phosphate.

The Evidence¶

Bioactive glasses show promise for:

Sensitivity: Good evidence for tubule occlusion and sensitivity reduction.

Remineralization: Promising in vitro data; clinical evidence growing.

Biofilm modification: Some evidence that the alkaline surface environment affects plaque composition.

Advantages¶

Controlled, sustained ion release
Alkaline surface effect (buffers acid)
Can incorporate fluoride (BioMinF)
Different mechanism from conventional remineralization—potentially complementary

Limitations¶

Less established than fluoride or n-HAp
Limited product availability in some markets
Higher cost than standard toothpaste

Arginine and Alkali-Generating Technologies¶

We touched on arginine earlier when discussing the ecological paradigm. As a remineralization technology, arginine represents something different: rather than providing minerals directly, it supports the bacteria that create favorable conditions for natural remineralization.

The Mechanism Revisited¶

Arginolytic bacteria (S. gordonii, S. sanguinis, etc.) metabolize arginine through the arginine deiminase system:

\[\text{Arginine} \rightarrow \text{Ornithine} + \text{NH}_3 + \text{CO}_2 + \text{ATP}\]

The ammonia (NH₃) produced raises plaque pH, counteracting acid from sugar-fermenting bacteria. Higher pH = more favorable remineralization conditions.

The Products¶

Colgate's "Sugar Acid Neutralizer" technology contains 1.5% arginine + calcium carbonate + fluoride.

Several studies show:⁴

Reduced demineralization in acid challenge models
Actual caries reduction in clinical trials
A 20% reduction in new caries lesions compared to fluoride alone

This is genuinely impressive. Adding arginine to fluoride toothpaste provides additional benefit beyond fluoride alone—a true synergy.

The Ecological Angle¶

What I particularly appreciate about arginine technology is that it works through the microbiome. Rather than ignoring or attacking oral bacteria, it feeds the beneficial ones. It's prebiotic dentistry.

This represents where I believe oral care is heading: understanding the ecosystem well enough to nudge it in favorable directions rather than burning it down and hoping for the best.

Peptide Technologies¶

Emerging research is exploring synthetic peptides designed to interact with tooth surfaces:

Amelogenin-Derived Peptides¶

Amelogenin is the primary protein in developing enamel, guiding crystal formation. Researchers have created peptide fragments that mimic amelogenin's function:

Promote ordered hydroxyapatite crystal growth
May regenerate enamel-like structures on demineralized surfaces
Still largely experimental

Statherin-Derived Peptides¶

Statherin controls mineralization in saliva, preventing premature precipitation while enabling controlled deposition on teeth. Synthetic statherin analogues are being explored for:

Enhanced calcium/phosphate delivery
Improved pellicle formation
Controlled remineralization

The Future of Peptide Therapy¶

These technologies are years from commercialization, but they represent a shift toward true regeneration rather than just remineralization. The holy grail would be a treatment that regrows enamel completely—something that seemed impossible a generation ago but now appears theoretically achievable.

Laser and Phototherapy¶

Emerging physical interventions may enhance remineralization:

Low-Level Laser Therapy (LLLT)¶

Some research suggests that specific wavelengths of light can:

Accelerate remineralization when combined with fluoride
Modify enamel surface properties
Potentially seal early lesions

The evidence is early, and clinical application remains limited.

Photodynamic Therapy¶

Already used for periodontal infections, photodynamic therapy uses light-activated compounds to generate reactive oxygen species that kill bacteria. Research is exploring less aggressive applications that might modulate biofilm composition rather than sterilize.

Probiotic Technologies¶

We discussed oral probiotics in the botanical section. From a technology perspective, the field is evolving:

Current Products¶

S. salivarius K12 and M18 lozenges (BLIS)
Various probiotic-containing toothpastes (variable quality)
Probiotic gums and mints

Future Directions¶

Engineered probiotics: Genetically modified bacteria designed to outcompete pathogens without producing acid. The SMaRT Replacement Therapy (S. mutans that can't make lactic acid) has been in development for 20+ years and may eventually reach market.⁵

Synbiotic approaches: Combining probiotics with prebiotics (like arginine) to give beneficial bacteria a competitive advantage.

Targeted bacteriocins: Antimicrobial peptides that kill specific pathogens while sparing commensals—precision weapons rather than broad-spectrum destruction.

Summary: The Remineralization Arsenal¶

Technology	Mechanism	Availability	Evidence	Best Use Case
Fluoride	Fluorapatite formation	Universal	Excellent	General population
n-HAp	Biomimetic mineral deposition	Growing	Good	Fluoride-avoiders, sensitivity
CPP-ACP	Stabilized mineral delivery	Moderate	Good	White spots, orthodontics
Bioactive glass	Controlled ion release	Limited	Moderate	Sensitivity, adjunctive use
Arginine	Microbiome-mediated pH	Growing	Good	Ecological approach, high risk
Peptides	Guided mineralization	Experimental	Early	Future regenerative therapy
Probiotics	Competitive colonization	Emerging	Moderate	Ecological management

The Future I See¶

After watching dental technology evolve for longer than your species has had dentistry, I can see where this is heading:

Personalization: Based on individual microbiome composition, genetic caries risk, dietary patterns, and salivary factors, interventions will be tailored rather than one-size-fits-all.

Ecological management: The antiseptic era will be remembered as a well-intentioned wrong turn. The future belongs to microbiome management—prebiotics, targeted probiotics, and environmental modifications.

True regeneration: Technologies that genuinely regrow lost enamel will eventually emerge. Not just remineralization of early lesions, but actual regeneration of structure.

Prevention over treatment: As we understand caries initiation better, prevention will become more effective. The need for restorative dentistry may decline substantially.

I find this genuinely hopeful. After millennia of watching humans lose teeth that could have been saved, I'm starting to see a future where dental decay becomes rare rather than common.

It can't happen soon enough. I'm tired. But for the first time in centuries, I think I might finally get back to my true work—the garden, the herbs, the teaching. The work that calls to me when I'm not called to your bedsides.

Reynolds, E. C. (1997). Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions. Journal of Dental Research, 76(9), 1587-1595. ↩
Andersson, A., et al. (2007). Effect of a dental cream containing amorphous cream phosphate complexes on white spot lesion regression assessed by laser fluorescence. Caries Research, 41(4), 268-273. ↩
Bioglass — Wikipedia. Larry Hench discovered the first bioactive glass at the University of Florida in 1969. ↩
Kraivaphan, P., et al. (2013). Two-year caries clinical study of the efficacy of novel dentifrices containing 1.5% arginine. Caries Research, 47(6), 582-590. ↩
Hillman, J. D., et al. (2007). Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie van Leeuwenhoek, 82(1), 361-366. ↩