【正文】 ase in local pH during mineralization in the gel system may be responsible for thepresent results.Figure 3. (A) Xray diffraction patterns of the mineralproducts obtained using a variety of fluoride concentrations at pH . (B) Expanded (300) Xray reflections ofthe mineral products. (a) F2free, (b) 2 ppm, (c) 20 ppm,(d) 50 ppm, (e) 100 ppm, (f) 200 ppm, (g) 500 ppm,(h) 1000 ppm, (i) 2020 ppm.Figure 4. Crystallinity (n) and solubility (l) of the minerals obtained in the fibrin gel using a variety of fluorideconcentrations at pH . Crystallinity was defined as theinverse of the halfvalue breadths at the (002) peak, andthe solubility of the minerals in the gel was defined as theratio of the eluted Ca ions to the initial Ca content in theposite gel.BIOMIMETIC FABRICATION OF FIBRIN/APATITE COMPOSITE MATERIAL 225Journal of Biomedical Materials Research Part AFigure 5. SEM images of crystal growth in the presence of 20 ppm fluoride at pH (Bar: 5 lm): (A) Fibrin gel。 (a–c) Mineralization in the solutionsystem: (a) noncontrolled pH, (b) pH , (c) pH 。 in the presence of up to 20 ppm fluorideions, it was the OCP and HAp mixture。and PO43–were diffused into the fibrin gel fromopposite sides to facilitate mineralization in the gel. (B)Fibrin gel size, 8 mm 3 mm (diameter 3 thickness): (a)Fibrin gel, (b) 4 h postmineralization, (c) 3 days postmineralization.BIOMIMETIC FABRICATION OF FIBRIN/APATITE COMPOSITE MATERIAL 223Journal of Biomedical Materials Research Part Ain the gel mineralization systems。, Rigaku。 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 inorganic propertiesof the posite materials during the mineralizationprocess.It is advantageous to use fibrin gel in tissue engineering, because it is biopatible and biodegradable. Moreover, fibrin can be obtained from the peripheral blood of any individual25,26。 tmatsudent.Contract grant sponsor: JSPS。 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。 calcium phosphate。 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。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。 biomineralization。 hydrogel。 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