【正文】 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。 biomineralization。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。 calcium phosphate。 tmatsudent.Contract grant sponsor: JSPS。, Rigaku。 in the presence of up to 20 ppm fluorideions, it was the OCP and HAp mixture。 an increase in fluoride ionconcentration resulted in a decrease in the number ofribbonlike OCP crystals. Finally, at fluoride ion concentration of 200 ppm fluoride ions, the entire areawas covered by needlelike FAp crystals (Fig. 6).Solubility experimentThe solubility of each sample was determined asthe ratio of the eluted Ca ions to the initial Ca content in the mineralized gel. As expected, the solubility decreased with an increase in fluoride concentration (Fig. 4).DISCUSSIONOver the past decade, a number of studies havebeen conducted on organic/inorganic positematerials for improving their mechanical properties,biodegradability, and biological affinity.28,29In thisstudy, we established a method for fabricating organic/inorganic material from fibrin and calciumphosphate by using bidirectional diffusion of the Caand PO4solutions into the fibrin gel. We also demonstrated that the characteristics of the mineralphase of this posite material could be controlledby altering the pH and fluoride ion concentration.First, we pared the mineral characteristicsformed in the gel diffusion system with thoseformed in the solution system. The crystallinity ofthe mineral generated in the gel system was higherthan that generated in the solution system. Fibrin gelprises a work of small fibrils, and this structure might attenuate ion diffusion and promote crystal growth in the gel. In the absence of fluoride ions,the minerals obtained in the gel diffusion systemwere DCPD under the noncontrolled pH conditions,the DCPD and OCP mixture at pH , and the OCPand HAp mixture at pH . Previous reports havesuggested that the pH condition suitable for DCPDsynthesis is acidic,30for OCP, it is neutral to mildlyacidic,31and for HAp, it is neutral to weakly alkaline.32The decrease 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。27:1399–1409.2. Tachibana A, Kaneko S, Tanabe T, Yamauchi K. Rapid fabrication of keratin–hydroxyapatite hybrid sponges towardosteoblast cultivation and differentiation. Biomaterials 2020。425:977–980.6. Du C, Falini G, Fermani S, Abbott C, MoradianOldak J.Supramolecular assembly of amelogenin nanospheres intobirefringent microribbons. Science 2020。279:40263–40266.10. Watanabe J, Akashi M. Nove