【正文】 Biomimetic fabrication of fibrin/apatite posite materialRui Yoh, Takuya Matsumoto, Junichi Sasaki, Taiji SohmuraDepartment of Oromaxillofacial Regeneration, Osaka University, 18 Yamadaoka, Suita, Osaka 5650871, JapanReceived 8 May 2020。 revised 12 September 2020。 accepted 24 September 2020Published online 17 December 2020 in Wiley InterScience (). DOI: Abstract: Bidirectional diffusion of the Ca and PO4solutions into the fibrin gel was performed at various pH conditions and fluoride concentrations to generate organic/inorganic posite materials mimicking biomineralization. Theminerals produced in this system had a higher crystallinitythan those generated by the solution mineralization system.The minerals generated in fibrin gel varied depending onthe pH conditions as follows: Dicalcium phosphate dihydrate (DCPD) in the noncontrolled pH solution, the DCPDand octacalcium phosphate (OCP) mixture at pH , andthe OCP and hydroxyapatite (HAp) mixture at pH .When fluoride ions were added in the range of 2–500 ppm,the minerals produced at pH altered from OCP/HAp toHAp/fluorapatite (FAp). In addition, the crystallinity of theobtained minerals increased with an increase in fluoride ionconcentration, and the solubility was inversely correlated tocrystallinity. In conclusion, we established a novel fabrication method for synthesizing organic/inorganic positematerials posed of fibrin and calcium phosphate andrevealed that the characteristics of the minerals in the synthesized material can be controlled by the fabrication condition. C211 2020 Wiley Periodicals, Inc. J Biomed Mater Res 87A:222–228, 2020Key words: bioinspired materials。 biomineralization。 calcium phosphate。 hydrogel。 fluorideINTRODUCTIONOrganic/inorganic posite materials are underintense investigation in the area of bone tissue engineering to enhance their affinity to biological tissues,to improve their mechanical properties, and to facilitate rapid bone regeneration.1,2Most of the organic/inorganic posite materials are fabricated using asimple mixture of originally organic and inorganicmaterials3,4。 however, the fabrication methods of theposite materials that mimic biological hard tissueformation are not well introduced.Biological hard tissues, such as bone and enamel,are formed by nucleation and crystal growth of calcium phosphate in the extracellular matrix (ECM) ofcells. For example, osteocalcin or other noncollagenous protein, which chemically bind with type I collagen, has a high affinity for hydroxyapatite (HAp).5Selfassembled amelogenin nanospheres regulate apatite crystal morphology during enamel formation.6Thus, ECM plays critical roles not only by providinga space to deposit mineral crystals but also by conducting nucleation, crystal morphology, and orientation of the biominerals with regard to hard tissuegrowth.7–9Several works have used calcification systems in various hydrogels and attempted to understand the role of the matrix protein in biomineralization.10,11For example, Boskey et al. established diffusion systems using gelatin and agarose gels anddemonstrated the promoting/inhibiting action of thenoncollagenous protein on HAp formation.12–14Hunter et al. used an acrylamide gel to investigatethe mineralization process in vitro.15,16Thus, formation of minerals in organic matrices is regarded asone of the mineralization methods that mimic hardtissue growth, and these organic/inorganic posite materials fabricated by the biomimetic processmight be useful in bone tissue engineering. However, the inorganic phase fabricated in the abovementioned gel systems mostly prised low crystalline apatite. It is desirable to control the propertiesof the inorganic phase in the posite materials foruse in bone tissue engineering, because the materialsrequire distinctive properties (., bioabsorbability)for each therapeutic application. To control this inorganic property, we attempted to fabricate the posite materials in a variety of conditions.Fluoride enhances the stabilization of the HApcrystals by substituting the hydroxyl ions in its crystalline lattice with fluoride ions. The fluoride ionCorrespondence to: T. Matsumoto。 tmatsu@dent.Contract grant sponsor: JSPS。 contract grant number:18680039Contract grant sponsor: COE Frontier BiodentistryProgramC2112020 Wiley Periodicals, Inc.concentration in serum is 0– ppm17。 however, itincreases to 800 ppm in the bone18and to 350–1000ppm in the enamel.19,20Thus, fluoride obviouslyplays a crucial role in the regulation of mineralproperties with regard to hard tissue growth.21–23Inaddition, the pH is also considered an important factor in the mineral phase during the mineralizationprocess.24Therefore, these factors might be usefulparameters for controlling the i