Self-Assembling Peptide P11-4

Karissa Grado and Morgan Fowler

LIT Dental Hygiene Program
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As dental professionals we know that dental caries is one of the most common dental

diseases among children and adults worldwide. Since caries are so prevalent we are always

trying to come up with new technology to treat this issue and stay on top of it to keep it under

control. Traditional treatment for caries is to apply a strong topical fluoride to the tooth, drill and

fill the cavity with an amalgam, TCR, crowns, or severe enough pull the tooth. A peptide is a

compound consisting of two or more amino acids linked in a chain. Self-assembling peptides are

peptides that undergo spontaneous assembly to form nanostructures and repair tissues. Peptide

P11-4 is a self-assembling peptide that treats white spot lesions in a non-invasive way that

requires no drilling on the tooth and is pain-free. Peptide P11-4 is similar in the way that it is

applied like a fluoride varnish or sealant on the tooth, but it works in a completely different way

and is 3x better. This new regenerative technology is painted on the surface of the carious lesion

and helps to stop the carious lesion from progressing any further. Peptide P11-4 has also been

shown to start the re-mineralization process of the tooth, as well as regenerate the tissues by

producing hydroxyapatite crystals beneficial in forming enamel. This material will be beneficial

for patients that have incipient lesions, chronic caries, and recurrent decay. By presenting this

research we hope to accomplish more widespread accepted treatment for caries. Since patients

will not have to go under the drill or receive injections, which is a main reason people put off

dental treatment. The advantages of this product are patients receive a non-surgical pain-free

treatment, which is welcomed among patients. The company Credentis has patented the

technology and named the product Curodont. The product is being widely used by dentists in

Europe and the company is awaiting approval for distribution of Curodont in the United States.

Once this technology is available for worldwide use in the field of dentistry, the way weve
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always known to treat caries will drastically change. We believe this change will be for the better

and greatly impact our field!

Researchers at the University of Leeds in England have developed a completely non-

invasive treatment that enables the patient to keep their natural teeth by combining peptide

monomers that form a three-dimensional matrix via hydrogen bonds (Credentis). Peptide P11-

4 is applied in a way that is very similar to a sealant. This magic fluid, Peptide P11-4, can be

prepared in water where it is considered as a low viscosity fluid. First, you will clean and dry the

tooth surface and use a 37% phosphoric acid for 30 seconds to roughen up the enamel surface for

the peptide to adhere to the lesion. After the tooth is prepped and ready, the next step is to paint

Curodont on the lesion and ensure moisture control until the solution is no longer visible. It

should take about 2 minutes for the peptide to no longer be visible on the surface. When painted

onto the incipient lesion, the fluid penetrates into the micro-pores caused by decay and the

presence of calcium ions trigger the self- assembly process, forming a scaffold (Kirkham). The

framework formed from Peptide P11-4 can attract calcium to promote the formation of new

hydroxyapatite crystals in the lesion, healing it from the inside out. The peptide then goes to

work on the enamel matrix [which] can be regenerated with calcium and phosphate ions from

the saliva (Jablonski-Momeni et al). This product however, requires that lesions be accurately

identified at an early stage of development (Jablonski-Momeni et al). Once this product is

applied, advise your patient not to brush the quadrant containing the treated tooth until Day 4.

The patients were asked to rinse the area of the mouth with a chlorhexidine mouthwash

(Brunton, et al). Once they can brush the quadrant use a soft bristle brush and toothpaste until

Day 8 when they go back for a review visit. After Day 8 the patient can return to their normal
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oral hygiene care. Peptide P11-4, also known as Curodont, is safe and has been approved for

clinical use within Europe.

The start of clinical development of peptides in dentistry began in 2007 and the first

clinical study for enamel regeneration began in 2010. Scientists have also been researching self-

assembling peptides in dentistry since 1997. Since then, many clinical trials have taken place to

prove this material to be safe and effective for repairing decayed areas on teeth. Seventy patients,

ages from eighteen to sixty-five, had to have qualified with two proximal carious lesions on

different teeth with at least one tooth in between (clinicaltrials.gov). The lesions must be fully

visible in the mouth and on radiographs. Any patients with a reduced salivary flow, significant

tooth wear, systemic disorder, pregnant, or involved with another clinical trial was not chosen for

this experiment. Lesions tested during the trial were on the occlusal, proximal, cervical 1/3 of the

tooth. It was also tested on white spot lesions. First the tooth was moistened with a 2% sodium

hypochlorite solution and rinsed. The surfaces were then slightly corroded with 37% phosphoric

acid and dried. Curodont was applied and allowed to work for about 5 minutes (Jablonski-

Momeni et al.). The results from these trials have shown that P11-4 can indeed reverse the

damage and regenerate the tooth tissue (University of Leeds). Outcomes of the product going to

work on a decayed lesion are significant changes in the color of the lesion, as well as the size.

Essentially, after 180 days of treatment the white spot lesion significantly disappears, showing

repair of the lesion. The study also showed that if the lesion was not completely gone, there was

at least a significant difference in the size and color was almost back to the normal color of the

rest of the tooth. Just to clarify, Curodont Repair is not a filler and should not be a substitute for a

filler. Curodont it needs to be applied before the white spot cavitates. Initially, Curodont is

between classical prevention and a filler, with the aim of avoiding (or at least significantly
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delaying) the filling and thus conserving the natural tooth structure. In general, the more active

the spots are the better the result, but if you are looking for perfect esthetics, a filling would be

best. Curodont repair is all about preserving the natural tooth structure and avoiding the deadly

cycle of restorations. These findings offer additional motivation for patients to keep their teeth

healthy (Jablonski-Momeni et al.). Since patients in the study felt comfortable with this non-

invasive treatment and followed specific criteria to care for the tooth once Curodont was applied,

patients felt more in control for their overall oral hygiene practices.

Curodont has been approved for use in dental offices in Europe and has been proven to be

safe and effective for treating and repairing carious lesions. Since the product has been shown to

be safe, there are a few side effects that can occur. During the trial, eleven adverse effects were

reported, but the two that were judged by the investigator as probably related to the protocol

used in the trial (Brunton, et al.) were dental hypersensitivity and sensitivity with corsodyl

mouth rinse. The other nine events reported during the trial were deemed not related to the study.

In the study, there was nothing said about what would happen if the product was applied wrong

or proper protocol procedures were not followed. In response, we feel that if the product was

applied wrong or proper care instructions were not followed, the effect would be that the lesion

would not have significant repair or show any changes at all. We believe Curodont is safe,

effective, and will be the go-to product for caries treatment.

The benefits of this product are that it is non-invasive, non-surgical, and pain-free.

Patients like that they do not have to get injections or go under the drill to repair their incipient

lesions. One main advantage of Curodont is that once its been applied it begins to work to

preserve and repair your natural tooth enamel by producing hydroxyapatite crystals. The cost of

the product is three hundred U.S. dollars or two hundred and fifty Euros for a box of 10
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applicators (good to treat 10 teeth). As we have discussed earlier, Curodont is being widely used

across Europe in their dental offices and is currently awaiting United States approval for

distribution. It could possibly take months or years before the FDA approves Curodont for use in

the United States. So far, dentists in Europe love the product and have not had any negative

feedback about Curodont. Since researching this product we feel that once it is approved for use

in the US, it will become a booming business and will dramatically impact the typical treatment

for incipient lesions. We feel that as long as you can work to preserve your natural tooth

structures and save your original teeth, this is best route to try first. This treatment for lesions

will become greatly accepted among patients for it being so simple, easy, and non-invasive.

Once this technology comes out on the market we conclude that the field of dentistry will

drastically change in the way we perform fillings on carious lesions. We believe this change will

definitely be for the better!

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References

Brunton, P. A., Davies, R. P. W., Burke, J. L., Smith, A., Aggeli, A., Brookes, S. J., &
Kirkham, J. (2013, August 23). Treatment of early caries lesions using biomimetic self
assembling peptides - a clinical safety trial. British Dental Journal, 215(4), 6.
doi:http://dx.doi.org.libproxy.lamar.edu/10.1038/sj.bdj.2013.741

Jablonski-Momeni, A., & Heinzel-Gutenbrunner, M. (2014, May 15). Efficacy of the self
assembling peptide P11-4 in constructing a remineralization scaffold on
artificially-induced enamel lesions on smooth surfaces. Journal Of Orofacial
Orthopedics/Fortschritte Der Kieferorthopadie, 75(3), 175.
doi:10.1007/s00056-014-0211-2

Prakash, A., Parsons, S.J., Kyle, S., & McPherson, M. J. (2012, July 3). Recombinant
production of self-assembling structured peptides using SUMO as a fusion
partner. Microbial Cell Factories, 11(1), 92-101. doi:10.1186/1475-2859-11
92

Schmidlin, P., Zobrist, Katja., Attin, Thomas., Wegehaupt, Florian. (2015, November 2). In vitro
re-hardening of artificial enamel caries lesions using enamel matrix proteins or self-
assembling peptides. Journal of Applied Oral Science Vol. 24 No.
http://dx.doi.org/10.1590/1678-77572015052

University of Leeds. (2011, August 23). Filling without drilling: Pain-free way of
tackling dental decay reverses acid damage and re-builds teeth. ScienceDaily.
Retrieved October 25, 2016 from
www.sciencedaily.com/releases/2011/08/110823115402.htm

http://clinicaltrials.gov/ct2/show/NCT02101255?term=peptide+p11-4&rank=4
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References: continued

http://credentis.com Regenerating Teeth: The New dimension of Self-Assembling Peptides.

(2017. Jan)