【正文】 l biomineralization for hydrogels: Electrophoresis approach accelerates hydroxyapatiteformation in hydrogels. Biomacromolecules 2020。75:494–501.14. Boskey AL, Boyan BD, Schwartz Z. Matrix vesicles promotemineralization in a gelatin gel. Calcif Tissue Int 1997。212:1509–1510.18. Boivin G, Chapuy MC, Baud CA, Meunier PJ. Fluoride content in human iliac bone: Results in controls, patients withfluorosis and osteoporotic patients treated with fluoride.J Bone Miner Res 1988。38:268–276.BIOMIMETIC FABRICATION OF FIBRIN/APATITE COMPOSITE MATERIAL 227Journal of Biomedical Materials Research Part A22. Aoba T, Shimizu Y, Taya Y, Soeno Y, Sato K, Miake Y. Fluoride and apatite formation in vivo and in vitro. J ElectronMicrosc (Tokyo) 2020。19:191–203.26. Valada JL, Hollingsbee DA, Menzies AR, Cornwell R, DoddRA. Reproducibillity of the mechanical properties of Vivostatsystem patientderived fibrin sealant. Biomaterials 2020。10:73–80.30. Martin RI, Brown PW. Phase equilibria among acid calciumphosphates. J Am Ceram Soc 1997。20:877–883.228 YOH ET AL.Journal of Biomedical Materials Research Part A。37:194–197.32. Okazaki M, Takahashi J, Kimura H. Crystallinity and solubility behavior of ironcontaining fluoridated hydroxyapatites.J Biomed Mater Res 1986。23:2241–2247.28. GonzalezMcQuire R, Green D, Walsh D, Hall S, ChaneChing JY, Oreffo RO, Mann S. Fabrication of hydroxyapatitesponges by dextran sulphate/amino acid templating. Biomaterials 2020。57:735–742.24. Liu C, Huang Y, Shen W, Cui J. Kiics of hydroxyapatiteprecipitation at pH 10 to 11. Biomaterials 2020。256:230–232.20. Mizuno T, Nakagaki H, Weatherell JA, Robinson C. Differences in fluoride concentrations in the enamel surfaces of lowerfirst premolars from young human males and females. ArchOral Biol 1990。317:59–64.16. Hunter GK, Goldberg HA. Modulation of crystal formationby bone phosphoproteins: Role of glutamic acidrich sequences in the nucleation of hydroxyapatite by bone sialoprotein.Biochem J 1994。17:387–396.12. Gericke A, Qin C, Spevak L, Fujimoto Y, Butler WT, SorensenES, Boskey AL. Importance of phosphorylation for osteopontin regulation of biomineralization. Calcif Tissue Int 2020。181:232–240.8. Rees SG, Hughes Wassell DT, Wanddington RJ, Embery G.Interaction of bone proteoglyacans and proteoglycan ponents with hydroxyapatite. Biochim Biophys Acta 2020。15:19–23.4. Nihouannen DL, Saffarzadeh A, Aquado E, Goyenvalle E,Gauthier O, Moreau F, Pitet P, Spaethe R, Daculsi G, LayrolleP. Osteogenic properties of calcium phosphate ceramics andfibrin glue based posites. J Mater Sci Mater Med 2020。 (C) 30 min postmineralization。 (a–c) Mineralization in the solutionsystem: (a) noncontrolled pH, (b) pH , (c) pH 。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。 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。 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。 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 , and