45ba4743cf8c89f159ad7a62a2d228ec scirep_a2020v10n254.pdf cc1af2540b2369cb56d7f41592277db7b4baa92e scirep_a2020v10n254.pdf 7d3faf27b24742f9a53d7f9d249f8be00c879ac55f4176ae3f4cd0d9e43f9957 scirep_a2020v10n254.pdf Title: Investigation of The Cellular Response to Bone Fractures: Evidence for Flexoelectricity Subject: Scientific Reports, doi:10.1038/s41598-019-57121-3 Keywords: Creator: Springer Producer: iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) CreationDate: Mon Jan 6 18:51:28 2020 CET ModDate: Wed Jan 8 15:34:52 2020 CET Tagged: no UserProperties: no Suspects: no Form: AcroForm JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 782.362 pts Page rot: 0 File size: 3946279 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ISDKMH+Corbel-Bold CID TrueType Identity-H yes yes yes 44 0 MinionPro-Regular Type 1C Custom yes no yes 46 0 QXLHPL+Corbel-Bold2 Type 1C WinAnsi yes yes yes 47 0 MinionPro-It Type 1C Custom yes no yes 49 0 VQFSPI+Corbel2 Type 1C WinAnsi yes yes yes 50 0 RNXWIP+Corbel CID TrueType Identity-H yes yes yes 51 0 MyriadPro-It Type 1C WinAnsi yes no yes 52 0 UUTMTJ+STIXGeneral-Regular Type 1C Custom yes yes yes 45 0 MinionPro-Bold Type 1C WinAnsi yes no yes 48 0 VQFSPI+Corbel2 Type 1C WinAnsi yes yes yes 341 0 EuclidSymbol Type 1C Custom yes no yes 75 0 STIXGeneral-Italic Type 1C Custom yes no yes 76 0 EuclidSymbol-Italic Type 1C Custom yes no no 200 0 ELAQDP+EuclidMathOne CID TrueType Identity-H yes yes yes 292 0 DMQKPR+TimesNewRomanPSMT Type 1C WinAnsi yes yes yes 293 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 12:06:55 CEST RepresentationInformation: scirep_a2020v10n254.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-06-17 15:11:32 CEST Size: 3946279 Format: PDF Version: 1.4 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 11. Sun, X. et al. Mechanical stretch induced calcium efflux from bone matrix stimulates osteoblasts. Bone 50, 581–591, https://doi.org/10.1016/j.bone.2011.12.015 (2012). :44' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 11. Sun, X. et al. Mechanical stretch induced calcium efflux from bone matrix stimulates osteoblasts. Bone 50, 581–591, https://doi.org/10.1016/j.bone.2011.12.015 (2012). :46' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 18. Vasquez-Sancho, F., Abdollahi, A., Damjanovic, D. & Catalan, G. Flexoelectricity in Bones. Advanced materials 30, https://doi.org/10.1002/adma.201705316 (2018). :54' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 18. Vasquez-Sancho, F., Abdollahi, A., Damjanovic, D. & Catalan, G. Flexoelectricity in Bones. Advanced materials 30, https://doi.org/10.1002/adma.201705316 (2018). :56' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 9. Verborgt, O., Gibson, G. J. & Schaffler, M. B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. Journal of bone and mineral research: the official journal of the American Society for :58' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Scheme 1. Schematic illustration of the experiment design. (A) Sample preparation and crack generation by a three-point bending system. A notch was created, then a load was applied parallel to the width of the sample with a sharp knife drived :59' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 1. Osteocytes’ reaction to cracking. Cell viability analysed by Live/Dead staining (A) before and (B) immediately after crack generation in HA substrate.:60' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 1. Osteocytes’ reaction to cracking. Cell viability analysed by Live/Dead staining (A) before and (B) immediately after crack generation in HA substrate.:61' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 1. Osteocytes’ reaction to cracking. Cell viability analysed by Live/Dead staining (A) before and (B) immediately after crack generation in HA substrate.:62' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate. (C:63' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Scheme 1. Schematic illustration of the experiment design. (A) Sample preparation and crack generation by a three-point bending system. A notch was created, then a load was applied parallel to the width of the sample with a sharp knife drived:64' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate. (:65' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate. (:66' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 3. Caspase-3/7 activity under flexoelectric stimulation of hydroxyapatite ceramics. (A) Brightfield scannint electron image of the base, centre and tip of the crack. (B) Live/Dead staining images. (C) merged images of the crack and :67' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀 椀渀㨀㘀㤩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐶㐮ㄶ㈠㈱㈮㜶㌠㐷㠮〸㈠㈰〮㘲㉝⽈⽎⽁值㰯丠㤴‰⁒㸾㸾੥湤潢樊㠶‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀 椀㨀㜀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄹ㔮㈰㘠ㄹ㈮㜶㌠㈰㤮ㄳ㠠ㄸ〮㘲㉝⽈⽎⽁值㰯丠㤵‰⁒㸾㸾੥湤潢樊㠷‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀 㨀㜀ㄩ⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐲㘮㔰㔠ㄹ㈮㜶㌠㐴ㄮ㌶㐠ㄸ〮㘲㉝⽈⽎⽁值㰯丠㤶‰⁒㸾㸾੥湤潢樊㠸‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀㨀㜀㌩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌷㐮ㄱ‱㘲⸷㘳″㠸⸸㜶‱㔰⸶㈲崯䠯丯䅐㰼⽎‹㜠〠刾㸾㸊敮摯扪ਸ㤠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀㨀㜀㐩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈱㘮ㄸㄠㄴ㈮㜶㌠㈳ㄮ〱‱㌰⸶㈲崯䠯丯䅐㰼⽎‹㠠〠刾㸾㸊敮摯扪ਹ〠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀㨀㜀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㔱㤮ㄵ㌠ㄴ㈮㜶㌠㔳㌮〵㔠ㄳ〮㘲㉝⽈⽎⽁值㰯丠㤹‰⁒㸾㸾੥湤潢樊㤱‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀 椀㨀㜀〩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛ㄹ㔮㈰㘠ㄹ㈮㜶㌠㈰㤮ㄳ㠠ㄸ〮㘲㉝⽈⽎⽁值㰯丠㤵‰⁒㸾㸾੥湤潢樊㠷‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀 㨀㜀ㄩ⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐲㘮㔰㔠ㄹ㈮㜶㌠㐴ㄮ㌶㐠ㄸ〮㘲㉝⽈⽎⽁值㰯丠㤶‰⁒㸾㸾੥湤潢樊㠸‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀㨀㜀㌩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌷㐮ㄱ‱㘲⸷㘳″㠸⸸㜶‱㔰⸶㈲崯䠯丯䅐㰼⽎‹㜠〠刾㸾㸊敮摯扪ਸ㤠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀㨀㜀㐩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈱㘮ㄸㄠㄴ㈮㜶㌠㈳ㄮ〱‱㌰⸶㈲崯䠯丯䅐㰼⽎‹㠠〠刾㸾㸊敮摯扪ਹ〠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀㨀㜀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㔱㤮ㄵ㌠ㄴ㈮㜶㌠㔳㌮〵㔠ㄳ〮㘲㉝⽈⽎⽁值㰯丠㤹‰⁒㸾㸾੥湤潢樊㤱‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀 㨀㜀ㄩ⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㐲㘮㔰㔠ㄹ㈮㜶㌠㐴ㄮ㌶㐠ㄸ〮㘲㉝⽈⽎⽁值㰯丠㤶‰⁒㸾㸾੥湤潢樊㠸‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀㨀㜀㌩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌷㐮ㄱ‱㘲⸷㘳″㠸⸸㜶‱㔰⸶㈲崯䠯丯䅐㰼⽎‹㜠〠刾㸾㸊敮摯扪ਸ㤠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀㨀㜀㐩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈱㘮ㄸㄠㄴ㈮㜶㌠㈳ㄮ〱‱㌰⸶㈲崯䠯丯䅐㰼⽎‹㠠〠刾㸾㸊敮摯扪ਹ〠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀㨀㜀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㔱㤮ㄵ㌠ㄴ㈮㜶㌠㔳㌮〵㔠ㄳ〮㘲㉝⽈⽎⽁值㰯丠㤹‰⁒㸾㸾੥湤潢樊㤱‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀渀㨀㜀㌩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㌷㐮ㄱ‱㘲⸷㘳″㠸⸸㜶‱㔰⸶㈲崯䠯丯䅐㰼⽎‹㜠〠刾㸾㸊敮摯扪ਸ㤠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀㨀㜀㐩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈱㘮ㄸㄠㄴ㈮㜶㌠㈳ㄮ〱‱㌰⸶㈲崯䠯丯䅐㰼⽎‹㠠〠刾㸾㸊敮摯扪ਹ〠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀㨀㜀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㔱㤮ㄵ㌠ㄴ㈮㜶㌠㔳㌮〵㔠ㄳ〮㘲㉝⽈⽎⽁值㰯丠㤹‰⁒㸾㸾੥湤潢樊㤱‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀愀㨀㜀㐩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㈱㘮ㄸㄠㄴ㈮㜶㌠㈳ㄮ〱‱㌰⸶㈲崯䠯丯䅐㰼⽎‹㠠〠刾㸾㸊敮摯扪ਹ〠〠潢樊㰼⽆‴⽔祰支䅮湯琯䑥獴⣾＀匀瀀爀椀渀最攀爀一愀琀甀爀攀开匀挀椀刀攀瀀开㔀㜀㄀㈀㄀⸀椀渀搀搀㫾￾￾￾￾￾￾￾＀䘀椀最甀爀攀 㓾￾＀⻾￾＠˾￾￾＀䘀氀攀砀漀攀氀攀挀琀爀椀挀椀琀礀 攀昀昀攀挀琀猀 愀爀漀甀渀搀 戀漀渀攀 洀椀挀爀漀挀爀愀挀欀猀 椀渀 搀椀昀昀攀爀攀渀琀 洀愀琀攀爀椀愀氀猀⸀ 䌀愀氀挀甀氀愀琀攀搀 昀氀攀砀漀攀氀攀挀琀爀椀挀 昀椀攀氀搀 搀椀猀琀爀椀戀甀琀椀漀渀 愀爀漀甀渀搀 愀 洀椀挀爀漀挀爀愀挀欀 椀渀 䄀㄀ 䠀䄀 愀渀搀 䈀㄀ 吀椀俾＀㋾＀⸀ 刀攀搀 挀椀爀挀氀攀 氀椀洀椀琀猀 琀栀攀 ㄠ欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀㨀㜀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㔱㤮ㄵ㌠ㄴ㈮㜶㌠㔳㌮〵㔠ㄳ〮㘲㉝⽈⽎⽁值㰯丠㤹‰⁒㸾㸾੥湤潢樊㤱‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 4. Flexoelectricity effects around bone microcracks in different materials. Calculated flexoelectric field distribution around a microcrack in (A1) HA and (B1) TiO2. Red circle limits the 1⁜琀欀嘀⼀洀 爀攀最椀漀渀Ⰰ 琀栀攀 洀椀渀椀洀甀洀 洀愀最渀椀琀甀搀攀 琀栀愀琀 挀㨀㜀㔩⽂潲摥牛〠〠そ⽓畢瑹灥⽌楮欯䉓㰼⽗‰⽔祰支䉯牤敲⽓⽓㸾⽒散瑛㔱㤮ㄵ㌠ㄴ㈮㜶㌠㔳㌮〵㔠ㄳ〮㘲㉝⽈⽎⽁值㰯丠㤹‰⁒㸾㸾੥湤潢樊㤱‰扪਼㰯䘠㐯呹灥⽁湮潴⽄敳琨SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate.:76' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrate:77' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 9. Verborgt, O., Gibson, G. J. & Schaffler, M. B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. Journal of bone and mineral research: the official journal of the American Society for:78' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 5. Osteoblasts mineralization by flexoelectricity. (A) Brightfield, Calcein and Xylenol Orange staining images of osteocytes cultured in HA samples over 15 days in (A1) stimulated and (A2) not stimulated samples. (B) OC expression aft:79' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 5. Osteoblasts mineralization by flexoelectricity. (A) Brightfield, Calcein and Xylenol Orange staining images of osteocytes cultured in HA samples over 15 days in (A1) stimulated and (A2) not stimulated samples. (B) OC expression af:80' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Scheme 2. Schematic of the role of flexoelectricity in bone repair and remodelling. Crack‐generated flexoelectricity (A) is theoretically large enough to induce osteocyte apoptosis (B), and increase osteoblasts migration and mineralization a:81' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 9. Verborgt, O., Gibson, G. J. & Schaffler, M. B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. Journal of bone and mineral research: the official journal of the American Society fo:82' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 9. Verborgt, O., Gibson, G. J. & Schaffler, M. B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. Journal of bone and mineral research: the official journal of the American Society f:86' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 21. McCullen, S. D. et al. Application of low-frequency alternating current electric fields via interdigitated electrodes: effects on cellular viability, cytoplasmic calcium, and osteogenic differentiation of human adipose-derived stem cell:91' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 21. McCullen, S. D. et al. Application of low-frequency alternating current electric fields via interdigitated electrodes: effects on cellular viability, cytoplasmic calcium, and osteogenic differentiation of human adipose-derived stem cel:95' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 1. Osteocytes’ reaction to cracking. Cell viability analysed by Live/Dead staining (A) before and (B) immediately after crack generation in HA substrate.:98' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substrat:99' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 5. Osteoblasts mineralization by flexoelectricity. (A) Brightfield, Calcein and Xylenol Orange staining images of osteocytes cultured in HA samples over 15 days in (A1) stimulated and (A2) not stimulated samples. (B) OC expression a:100' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Scheme 1. Schematic illustration of the experiment design. (A) Sample preparation and crack generation by a three-point bending system. A notch was created, then a load was applied parallel to the width of the sample with a sharp knife drive:101' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 1. Osteocytes’ reaction to cracking. Cell viability analysed by Live/Dead staining (A) before and (B) immediately after crack generation in HA substrate.:102' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 2. Osteocytes’ reaction to mechanical stimulation of already existing cracks. (A) Brightfield optical micrograph of the crack prior to culture. (B) Live/Dead staining image of the culture on the crack before bending the substra:103' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Figure 5. Osteoblasts mineralization by flexoelectricity. (A) Brightfield, Calcein and Xylenol Orange staining images of osteocytes cultured in HA samples over 15 days in (A1) stimulated and (A2) not stimulated samples. (B) OC expression :104' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd:Scheme 1. Schematic illustration of the experiment design. (A) Sample preparation and crack generation by a three-point bending system. A notch was created, then a load was applied parallel to the width of the sample with a sharp knife driv:105' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 19. Zubko, P., Catalan, G. & Tagantsev, A. K. Flexoelectric Effect in Solids. Annual Review of Materials Research 43, 387–421, https://doi.org/10.1146/annurev-matsci-071312-121634 (2013). :107' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 18. Vasquez-Sancho, F., Abdollahi, A., Damjanovic, D. & Catalan, G. Flexoelectricity in Bones. Advanced materials 30, https://doi.org/10.1002/adma.201705316 (2018). :108' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 18. Vasquez-Sancho, F., Abdollahi, A., Damjanovic, D. & Catalan, G. Flexoelectricity in Bones. Advanced materials 30, https://doi.org/10.1002/adma.201705316 (2018). :109' cannot be found Offset: 3445990 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_57121.indd: 19. Zubko, P., Catalan, G. & Tagantsev, A. K. Flexoelectric Effect in Solids. Annual Review of Materials Research 43, 387–421, https://doi.org/10.1146/annurev-matsci-071312-121634 (2013). :111' cannot be found Offset: 3445990 MIMEtype: application/pdf PDFMetadata: Objects: 523 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: EN Outlines: Item: Title: Investigation of The Cellular Response to Bone Fractures: Evidence for Flexoelectricity Children: Item: Title: Results Children: Item: Title: Osteocyte apoptosis around bone microcracks. Item: Title: Apoptotic effects of crack-generated flexoelectricity on osteocytes. Item: Title: Mineralizing effects of fracture stimulation. Item: Title: Discussion Item: Title: Methods Children: Item: Title: Substrate materials. Item: Title: Cleaning protocol of substrates. Item: Title: Crack generation. Item: Title: Cell Culture. Item: Title: Sample stimulation. Item: Title: Live/dead staining. Item: Title: Cell proliferation assay. Item: Title: Caspase-3/7 staining. Item: Title: Xylenol orange staining. Item: Title: qRT-PCR analyses. Item: Title: Scanning electron microscopy. Item: Title: Statistical analysis. Item: Title: Appendix: Analytical Calculations Item: Title: Acknowledgements Item: Title: Scheme 1 Schematic illustration of the experiment design. Item: Title: Figure 1 Osteocytes’ reaction to cracking. Item: Title: Figure 2 Osteocytes’ reaction to mechanical stimulation of already existing cracks. Item: Title: Figure 3 Caspase-3/7 activity under flexoelectric stimulation of hydroxyapatite ceramics. Item: Title: Figure 4 Flexoelectricity effects around bone microcracks in different materials. Item: Title: Figure 5 Osteoblasts mineralization by flexoelectricity. Item: Title: Scheme 2 Schematic of the role of flexoelectricity in bone repair and remodelling. 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true CIDFontType2: Font: BaseFont: ISDKMH+Corbel-Bold CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: ISDKMH+Corbel-Bold Flags: Symbolic FontBBox: -556, -239, 1155, 952 FontFile2: true Font: BaseFont: RNXWIP+Corbel CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: RNXWIP+Corbel Flags: Symbolic FontBBox: -553, -239, 1110, 952 FontFile2: true Font: BaseFont: ELAQDP+EuclidMathOne CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: ELAQDP+EuclidMathOne Flags: Serif, Symbolic FontBBox: -113, -316, 1395, 927 FontFile2: true XMP: application/pdf doi:10.1038/s41598-019-57121-3 Springer US Scientific Reports, doi:10.1038/s41598-019-57121-3 Investigation of The Cellular Response to Bone Fractures: Evidence for Flexoelectricity 10.1038/s41598-019-57121-3 http://dx.doi.org/10.1038/s41598-019-57121-3 journal Scientific Reports © 2019, The Author(s) 2045-2322 10.1038/s41598-019-57121-3 Springer 2020-01-08T15:34:52+01:00 2020-01-06T23:21:28+05:30 2020-01-08T15:34:52+01:00 True iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) VoR uuid:152646b3-3276-4639-a360-4d86ee8ebdd6 uuid:f5a8986f-b8ab-4919-b572-b3131f434f4e default 1 converted uuid:bc95512d-84c3-4bbf-bfd1-dceb6761fe18 converted to PDF/A-2b pdfToolbox 2020-01-06T23:22:08+05:30 2 B http://ns.adobe.com/xap/1.0/mm/ xmpMM XMP Media Management Schema internal UUID based identifier for specific incarnation of a document InstanceID URI internal The common identifier for all versions and renditions of a document. OriginalDocumentID URI http://ns.adobe.com/pdf/1.3/ pdf Adobe PDF Schema internal A name object indicating whether the document has been modified to include trapping information Trapped Text http://ns.adobe.com/pdfx/1.3/ pdfx pdfx internal ID of PDF/X standard GTS_PDFXVersion Text internal Conformance level of PDF/X standard GTS_PDFXConformance Text internal Company creating the PDF Company Text internal Date when document was last modified SourceModified Text internal Mirrors crossmark:DOI doi Text http://www.aiim.org/pdfa/ns/id/ pdfaid PDF/A ID Schema internal Part of PDF/A standard part Integer internal Amendment of PDF/A standard amd Text internal Conformance level of PDF/A standard conformance Text http://prismstandard.org/namespaces/basic/2.0/ prism Prism external The aggregation type specifies the unit of aggregation for a content collection. Comment PRISM recommends that the PRISM Aggregation Type Controlled Vocabulary be used to provide values for this element. Note: PRISM recommends against the use of the #other value currently allowed in this controlled vocabulary. In lieu of using #other please reach out to the PRISM group at info@prismstandard.org to request addition of your term to the Aggregation Type Controlled Vocabulary. aggregationType Text external Copyright copyright Text external The Digital Object Identifier for the article. The DOI may also be used as the dc:identifier. If used as a dc:identifier, the URI form should be captured, and the bare identifier should also be captured using prism:doi. If an alternate unique identifier is used as the required dc:identifier, then the DOI should be specified as a bare identifier within prism:doi only. If the URL associated with a DOI is to be specified, then prism:url may be used in conjunction with prism:doi in order to provide the service endpoint (i.e. the URL). doi Text external ISSN for an electronic version of the issue in which the resource occurs. Permits publishers to include a second ISSN, identifying an electronic version of the issue in which the resource occurs (therefore e(lectronic)Issn. If used, prism:eIssn MUST contain the ISSN of the electronic version. See prism:issn. issn Text external Title of the magazine, or other publication, in which a resource was/will be published. Typically this will be used to provide the name of the magazine an article appeared in as metadata for the article, along with information such as the article title, the publisher, volume, number, and cover date. Note: Publication name can be used to differentiate between a print magazine and the online version if the names are different such as “magazine” and “magazine.com.” publicationName Text external This element provides the url for an article or unit of content. The attribute platform is optionally allowed for situations in which multiple URLs must be specified. PRISM recommends that a subset of the PCV platform values, namely “mobile” and “web”, be used in conjunction with this element. NOTE: PRISM recommends against the use of the #other value allowed in the PRISM Platform controlled vocabulary. 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