The use of Fluorohydroxyapatite:

Wang L, Zhang H, Deng Y, Luo Z, Liu X, Wei S. Study of oral microbial adhesion and biofilm formation on the surface of nano-fluorohydroxyapatite/polyetheretherketone composite. Zhonghua Kou Qiang Yi Xue Za Zhi. 2015 Jun;50(6):378-82. 

Abstract. Objective: To develop novel polyetheretherketone (PEEK) based nanocomposites which possess the favorable antibacterial property, and to investigate the oral microbial adhesion and biofilm formation on the surfaces of PEEK, nano-fluorohydroxyapatite (n-FHA)-PEEK and nano-hydroxyaptite (n-HA)-PEEK. Methods: The bacterial adhesion and biofilm formation on the surfaces of n-FHA-PEEK, n-HA-PEEK were investigated via microbial viability assay kit and laser scanning confocal microscope (LSCM), respectively, with pure PEEK as control group.....Conclusions: The combination of n-HA, especially for the n-FHA could inhibit the bacteria adhesion and accelerate the bacterial death, eventually may have an influence on the structure of biofilms and reduce the risk of peri-implantitis. Therefore, n-FHA-PEEK nanocomposites presented a good prospect for clinical applications as dental implant materials.

Tahriri M, Moztarzadeh F. Preparation, characterization, and in vitro biological evaluation of PLGA/nano-fluorohydroxyapatite (FHA) microsphere-sintered scaffolds for biomedical applications. Appl Biochem Biotechnol. 2014 Mar;172(5):2465-79. doi: 10.1007/s12010-013-0696-y. 

Abstract. In this research, the novel three-dimensional (3D) porous scaffolds made of poly(lactic-co-glycolic acid) (PLGA)/nano-fluorohydroxyapatite (FHA) composite microspheres was prepared and characterize for potential bone repair applications. We employed a microsphere sintering method to produce 3D PLGA/nano-FHA scaffolds composite microspheres. The mechanical properties, pore size, and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLGA/nano-FHA ratio. The experimental results showed that the PLGA/nano-FHA (4:1) scaffold sintered at 90 °C for 2 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, MTT assay and alkaline phosphatase activity (ALP activity) results ascertained that a general trend of increasing in cell viability was seen for PLGA/nano-FHA (4:1) scaffold sintered at 90 °C for 2 h by time with compared to control group. Eventually, obtained experimental results demonstrated PLGA/nano-FHA microsphere-sintered scaffold deserve attention utilizing for bone tissue engineering.

Tahriri M, Moztarzadeh F. Preparation, characterization, and in vitro biological evaluation of PLGA/nano-fluorohydroxyapatite (FHA) microsphere-sintered scaffolds for biomedical applications. Appl Biochem Biotechnol. 2014 Mar;172(5):2465-79. doi: 10.1007/s12010-013-0696-y. 

Abstract. In this research, the novel three-dimensional (3D) porous scaffolds made of poly(lactic-co-glycolic acid) (PLGA)/nano-fluorohydroxyapatite (FHA) composite microspheres was prepared and characterize for potential bone repair applications. We employed a microsphere sintering method to produce 3D PLGA/nano-FHA scaffolds composite microspheres. The mechanical properties, pore size, and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLGA/nano-FHA ratio. The experimental results showed that the PLGA/nano-FHA (4:1) scaffold sintered at 90 °C for 2 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, MTT assay and alkaline phosphatase activity (ALP activity) results ascertained that a general trend of increasing in cell viability was seen for PLGA/nano-FHA (4:1) scaffold sintered at 90 °C for 2 h by time with compared to control group. Eventually, obtained experimental results demonstrated PLGA/nano-FHA microsphere-sintered scaffold deserve attention utilizing for bone tissue engineering.

Borzabadi-Farahani A, Borzabadi E, Lynch E. Nanoparticles in orthodontics, a review of antimicrobial and anti-caries applications. Acta Odontol Scand. 2014 Aug;72(6):413-7. doi: 10.3109/00016357.2013.859728. 

Abstract. Nanoparticles (NPs) are insoluble particles smaller than 100 nm in size. In order to prevent microbial adhesion or enamel demineralization in orthodontic therapy, two broad strategies have been used. These are incorporating certain NPs into orthodontic adhesives/cements or acrylic resins (nanofillers, silver, TiO2, SiO2, hydroxyapatite, fluorapatite, fluorohydroxyapatite) and coating surfaces of orthodontic appliances with NPs (i.e. coating bracket surfaces with a thin film of nitrogen-doped TiO2). Although the use of NPs in orthodontics can offer new possibilities, previous studies investigated the antimicrobial or physical characteristic over a short time span, i.e. 24 hours to a few weeks, and the limitations of in vitro studies should be recognized. Information on the long-term performance of orthodontic material using nanotechnology is lacking and necessitates further investigation and so do possible safety issues (toxicity), which can be related to the NP sizes

Zhao H, Wang F, Chen X, Wei Z, Yu D, Jiang Z. The formation mechanism of the beta-TCP phase in synthetic fluorohydroxyapatite with different fluorine contents. Biomed Mater. 2010 Aug;5(4):045011. doi: 10.1088/1748-6041/5/4/045011. 

Abstract. Synthetic hydroxyapatite (HAP) and fluorohydroxyapatite (F(x)AP) products may form the beta-tricalcium phosphate (beta-TCP) phase in a calcination process. The beta-TCP phase has a greater tendency for degradation in vivo than HAP and F(x)AP. Hence, controlling the content of the beta-TCP phase in the apatite is a pivotal factor to affect their lifetime and stability in vivo. It is particularly important to explore the formation mechanism of the beta-TCP phase in synthetic apatite. In this work, F(x)AP products with a chemical composition of Ca(10)(PO(4))(6)(OH)(2-x)F(x) are synthesized, with x = 0, 0.4, 0.8, 1.2, 1.6 and 2.0, using a precipitation method and a calcination process. The effect of fluorine substitution for hydroxyl is investigated by using x-ray diffraction analysis, Fourier transform infrared spectroscopy, and thermogravimetry and differential thermal analysis. The results show that addition of fluorine forms F(x)AP that exhibits high thermal stability. The beta-TCP phase produced as a result of the structural refinement by heat treatment is gradually reduced and dramatically suppressed with the fluorine content.

Lee CY, Rohrer MD, Prasad HS, Stover JD, Suzuki JB. Sinus grafting with a natural fluorohydroxyapatite for immediate load: a study with histologic analysis and histomorphometry. J Oral Implantol. 2009;35(4):164-75. doi: 10.1563/1548-1336-35.4.164.

Abstract. The goal of this retrospective study was to evaluate the survival rates of dental implants placed in sinuses grafted with a 50:50 composite ratio of autogenous bone and a natural flourohydroxyapatite (FHA) combined with platelet-rich plasma (PRP) using an immediate-load protocol. The authors hypothesized that a 50:50 composite ratio of FHA and autogenous bone combined with PRP would permit immediate loading without compromising implant survival rates. Eleven patients with bilateral partial edentulism of the posterior maxilla were enrolled in this retrospective study. Autogenous bone used in the graft procedure was harvested from the tibia of the left lower extremity. Each patient was grafted with a 50:50 composite ratio of autogenous bone and FHA. Membranes were not used to cover the lateral wall osteotomy site. Platelet-rich plasma was added to the graft material to accelerate and enhance bone regeneration. Four to 6 months after the grafting procedure, 37 hydroxyapatite-coated dental implants were surgically placed and immediately loaded between 72 hours and 5 days later with custom titanium abutments and acrylic provisional restorations placed out of functional occlusion. Six months later, definitive ceramometal restorations were cemented on to the custom abutments. Patients were observed over a 52-week period. The overall implant survival rate was 97.3%. Histologic and histomorphometric analysis of core samples revealed formation of new vital bone in different graft specimens ranging from 23% to 34%. In each core bone sample, 100% of the bone sample was determined to be vital. In the grafted maxillary sinus, the natural FHA combined with autogenous bone in a 50:50 composite ratio with PRP is a suitable graft material permitting immediate load without compromising implant survival rates while decreasing the overall healing time.

Klongnoi B, Rupprecht S, Kessler P, Zimmermann R, Thorwarth M, Pongsiri S, Neukam FW, Wiltfang J, Schlegel KA. Lack of beneficial effects of platelet-rich plasma on sinus augmentation using a fluorohydroxyapatite or autogenous bone: an explorative study. J Clin Periodontol. 2006 Jul;33(7):500-9. doi: 10.1111/j.1600-051X.2006.00938.x. 

Abstract. Background: Maxillary sinus augmentation is frequently necessary before placement of dental implants in the posterior maxilla. Besides autogenous bone graft, various bone substitutes have been used, with favourable results. Although platelet-rich plasma (PRP) has been used in the field of oral and maxillofacial surgery for years, its beneficial effects on osseous regeneration still remain unclear. The aim of this study was to evaluate the short and long time effects of PRP on single-stage sinus augmentation using autogenous bone or a fluorohydroxyapatite (Algipore) in a randomized prospective animal study....Results: The grafting materials chosen showed increasing levels of BIC and newly formed bone throughout the period of observation in both PRP and non-PRP groups. Adding PRP resulted in lower BIC and newly formed bone compared with autogenous bone grafts or Algipore alone. However, a statistical significance was not found. The percentages of the remaining bone substitute in both the PRP and non-PRP groups were closely comparable in all observation periods. Conclusions: The application of PRP could not reveal significant beneficial effects on the BIC, the percentage of the newly formed bone and the remaining bone substitute in this study.

Schopper C, Moser D, Sabbas A, Lagogiannis G, Spassova E, König F, Donath K, Ewers R. The fluorohydroxyapatite (FHA) FRIOS Algipore is a suitable biomaterial for the reconstruction of severely atrophic human maxillae. Clin Oral Implants Res. 2003 Dec;14(6):743-9. doi: 10.1046/j..2003.00959.x. 

Abstract. Grafting of the maxillary sinus is an established treatment modality to provide sufficient bone for the fixation of dental implants. We stated the hypothesis that the porous fluorohydroxyapatitic (FHA) biomaterial FRIOS Algipore could be used as a suitable biomaterial for sinus grafting in severely atrophic maxillae. To investigate the accuracy of our hypothesis, 69 trephine specimens from 26 patients who received maxillary sinus grafting with FRIOS Algipore were retrieved during the installation of dental implants. The specimens were processed undecalcified and subjected to histomorphological and histomorphometrical examination. After a mean healing time of 7 months, 23.0% (+/-8.3) new bone had formed around the implanted particles. Bone formation was also evident within the pores of the particles. Statistical analysis indicated that bone formation originated from the sinus floor. Particles provided scaffolding for the promotion of newly formed bone towards apical sinus portions. Mineral dissolution from the walls of the pores was observed prior to and during bone apposition. Thereafter, portions of the particles were resorbed during bone remodeling and replaced by newly formed bone. The present investigation shows that the biomaterial FRIOS Algipore is a suitable biomaterial for sinus grafting of severely atrophic maxillae.

Effects of incorporation of nano-fluorapatite or nano-fluorohydroxyapatite on a resin-modified glass ionomer cement.
Lin J, Zhu J, Gu X, Wen W, Li Q, Fischer-Brandies H, Wang H, Mehl C.
Acta Biomater. 2011 Mar;7(3):1346-53. doi: 10.1016/j.actbio.2010.10.029.

Alshemary AZ, Pazarçeviren EA, Dalgic AD, Tezcaner A, Keskin D, Evis Z. Nanocrystalline Zn2+ and SO42- binary doped fluorohydroxyapatite: A novel biomaterial with enhanced osteoconductive and osteoinconductive properties. Mater Sci Eng C Mater Biol Appl. 2019 Nov;104:109884. doi: 10.1016/j.msec.2019.109884. Epub 2019 Jun 12. PMID: 31500005. 

Fluorohydroxyapatite is also known as fluorapatite.

The amount of fluoride and fluorine in bones is influenced by several factors, including age.  Fluoride is incorporated in teeth, bones and, by replacing the hydroxyl ion in hydroxyapatite, fluorohydroxyapatite is formed, which is present for example in tooth enamel.

 is a mineral similar to hydroxyapatite, a form of calcium phosphate naturally found in teeth and bones, but with added fluoride. This ingredient is widely used in oral care products, such as toothpaste and dental treatments, for its remineralizing and strengthening properties. Fluorohydroxyapatite helps reinforce tooth enamel, prevent cavities, and promote the repair of small dental lesions.

Chemical Composition and Structure
Fluorohydroxyapatite is a variant of hydroxyapatite where some hydroxide ions (OH-) are replaced by fluoride ions (F-). This substitution enhances the acid resistance of fluorohydroxyapatite, improving its ability to protect teeth from demineralization and acid attacks produced by bacteria.

Physical Properties
Fluorohydroxyapatite appears as a fine white powder, soluble in acids but insoluble in water. It has a crystalline structure similar to tooth enamel, allowing it to naturally bond to the tooth surface and integrate into the remineralization process.

Production Process
Fluorohydroxyapatite is synthetically produced through a reaction involving calcium, phosphate, and fluoride compounds under controlled conditions. This process replicates the chemical and physical structure of the material found in teeth, making it suitable for use in oral health products.

• Hydroxyapatite - Hydroxyapatite is a naturally occurring mineral form of calcium phosphate. It serves as the main raw material for the synthesis of fluorohydroxyapatite. Hydroxyapatite can be obtained from various sources, including bone or synthesized through chemical processes.
• Fluoride compounds - Fluoride compounds, such as sodium fluoride or ammonium fluoride, are used as sources of fluoride ions in the synthesis of fluorohydroxyapatite. These compounds provide the necessary fluorine ions for the substitution of hydroxyl ions in hydroxyapatite.

The synthesis process takes place in several stages:

• Preparation of Precursors. Precursors are prepared, typically calcium nitrate tetrahydrate (Ca(NO3)2.4H2O), phosphorus pentoxide (P2O5) and ammonium fluoride (NH4F). These provide calcium, phosphorus, and fluorine components, respectively.
• Sol-Gel process. The precursors are mixed in a solvent to form a sol, a colloidal suspension of solid particles. The sol is then gelled to form a solid net, capturing the liquid component within its structure.
• Spin Coating. The sol is deposited on a substrate, such as titanium, and then spun at high speed to spread the sol evenly across the substrate and form a thin film.
• Heat treatment. The coated substrate is heated (fired) to temperatures between 500 and 800 ºC. This process, known as calcination, helps to consolidate the film and improve its crystallinity, forming fluorohoxyapatite.
• Characterization. The final product is characterized using techniques such as X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) to confirm the formation of fluorohydroxyapatite.

What it is used for and where

Medical

Drug delivery systems: fluorohydroxyapatite nanoparticles have been studied as carriers for controlled drug delivery. These nanoparticles can encapsulate therapeutic agents and release them in a controlled manner, enabling localised and sustained drug delivery to the desired site.

Bone grafts and tissue engineering: fluorohydroxyapatite has been explored as a material for bone grafts and scaffolds in tissue engineering applications. Its biocompatibility and similarity to natural bone mineral make it suitable for promoting bone regeneration and integration with surrounding tissues.

Dentistry

Dental coatings and surface treatments: fluorohydroxyapatite coatings can be applied to dental implants, orthodontic brackets and other dental devices to improve their biocompatibility and osseointegration (the bonding of the implant to the surrounding bone). The addition of fluoride in fluorohydroxyapatite coatings can provide antimicrobial properties and prevent biofilm formation.

Enamel repair and remineralisation: fluorohydroxyapatite has the ability to promote remineralisation and repair of enamel. When incorporated into oral hygiene products such as toothpaste or mouthwash, it can help prevent caries, strengthen tooth enamel and reduce the risk of caries.

Dental fillings and restorations: fluorohydroxyapatite can be used as a component in dental composites and prosthetic materials. It provides improved mechanical properties, better wear resistance and greater resistance to acid attack than conventional materials. These properties make fluorohydroxyapatite  a suitable material for dental fillings, crowns and other dental restorations.

Cosmetics

Oral care agent. This ingredient can be placed in the oral cavity to improve and/or maintain oral hygiene and health, to prevent or improve a disorder of the teeth, gums, mucous membrane. It provides cosmetic effects to the oral cavity as a protector, cleanser, deodorant.

Health and Safety Considerations

Safety in Use
Fluorohydroxyapatite is considered safe for use in oral care products. It is well tolerated and does not cause significant side effects when used as directed. It is not known to cause irritation or allergic reactions.

Allergic Reactions
Allergic reactions to fluorohydroxyapatite are extremely rare. However, individuals with sensitivities to similar ingredients should consult a healthcare provider before use.

Toxicity and Carcinogenicity
There is no evidence that fluorohydroxyapatite is toxic or carcinogenic. It is widely used in oral care products and considered a safe ingredient when used within approved concentrations.

Environmental and Safety Considerations
As a synthetic mineral, fluorohydroxyapatite is biodegradable and poses no significant environmental threat. The production process, when managed properly, has a limited environmental impact.

Regulatory Status
Fluorohydroxyapatite is approved for use in oral care products in many regions, including the European Union and the United States. It is regarded as a safe and highly effective ingredient for cavity prevention and enamel strengthening.

Studies

Fluorohydroxyapatite is a mineral composed of fluo and hydroxyapatite. Hydroxyapatite is a mineral composed mainly of calcium and is present in the human body and milk in good quantities and is found in bones and teeth where it acts as a shield for caries. However, when used as a food additive, this study on nanoparticles draws consumers' attention to the dangers of prolonged use (1).

Various strategies are used in the prevention of caries, including the use of fluoride and hydroxyapatite nanoparticles. Two new noninvasive repair techniques using fluorohydroxyapatite crystals are described here (2).

Nanoparticles of fluorohydroxyapatite in combination with polyetheretheretherketone led to an improvement in the use of polyetheretheretherketone, a good component, but which had shown little binding capacity with natural bone tissue and lack of antibacterial activity (3).

Studies and insights on fluorohydroxyapatite

References_________________________________________________________________________

(1) Setyawati MI, Sevencan C, Bay BH, Xie J, Zhang Y, Demokritou P, Leong DT Nano-TiO2 Drives Epithelial-Mesenchymal Transition in Intestinal Epithelial Cancer Cells.  Small. 2018 Jul;14(30):e1800922. doi: 10.1002/smll.201800922.

(2) Clarkson BH, Exterkate RA. Noninvasive dentistry: a dream or reality? Caries Res. 2015;49 Suppl 1:11-7. doi: 10.1159/000380887. Epub 2015 Apr 13. PMID: 25871414.

(3) Wang L, He S, Wu X, Liang S, Mu Z, Wei J, Deng F, Deng Y, Wei S. Polyetheretherketone/nano-fluorohydroxyapatite composite with antimicrobial activity and osseointegration properties. Biomaterials. 2014 Aug;35(25):6758-75. doi: 10.1016/j.biomaterials.2014.04.085.