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Qhia ib lub carousel ntawm peb slides ib zaug.Siv cov nyees khawm dhau los thiab Tom ntej kom txav mus los ntawm peb qhov swb ib zaug, lossis siv cov khawm slider thaum kawg kom txav mus los ntawm peb qhov swb ib zaug.
Qhov kev txwv ntawm fibrous hydrogels rau qhov nqaim capillaries yog qhov tseem ceeb hauv kev siv tshuaj lom neeg thiab biomedical systems.Kev nruj thiab uniaxial compression ntawm fibrous hydrogels tau kawm ntau, tab sis lawv cov lus teb rau biaxial tuav hauv capillaries tseem tsis tau tshawb nrhiav.Ntawm no, peb ua kom pom kev sim thiab theoretically tias filamentous gels teb qhov zoo sib txawv rau kev txwv ntau dua li cov saw hloov tau yooj yim vim yog qhov tsis sib xws hauv cov khoom siv kho tshuab ntawm cov khoom siv filaments, uas yog mos hauv compression thiab nruj hauv nro.Nyob rau hauv kev tuav ruaj khov, cov fibrous gel nthuav tawm me ntsis elongation thiab asymptotic txo qis hauv biaxial Poisson tus piv rau xoom, ua rau muaj zog gel compaction thiab cov kua dej tsis zoo los ntawm cov gel.Cov txiaj ntsig no qhia txog kev tiv thaiv ntawm stretched occlusive thrombi rau lysis los ntawm cov neeg ua haujlwm kho mob thiab txhawb txoj kev txhim kho ntawm endovascular embolization los ntawm fibrous gels kom nres vascular los ntshav lossis inhibit cov ntshav ntawm cov qog.
Fibrous tes hauj lwm yog cov qauv tsim thiab kev ua haujlwm ntawm cov ntaub so ntswg thiab cov cell nyob.Actin yog ib qho tseem ceeb ntawm cytoskeleton1;fibrin yog ib qho tseem ceeb hauv kev kho mob thiab thrombus tsim 2, thiab collagen, elastin thiab fibronectin yog cov khoom ntawm extracellular matrix nyob rau hauv cov tsiaj kingdom3.Rov qab cov tes hauj lwm ntawm fibrous biopolymers tau dhau los ua cov ntaub ntawv nrog kev siv dav hauv cov ntaub so ntswg engineering4.
Filamentous tes hauj lwm sawv cev rau ib chav kawm ntawm cov khoom siv roj ntsha nrog cov khoom siv kho tshuab uas txawv ntawm cov tes hauj lwm hloov tau yooj yim molecular5.Qee yam ntawm cov khoom no tau hloov zuj zus nyob rau hauv chav kawm ntawm evolution los tswj cov lus teb ntawm cov teeb meem lom neeg rau deformation6.Piv txwv li, fibrous tes hauj lwm qhia linear elasticity ntawm me me strains7,8 thaum nyob rau hauv loj hom lawv pom muaj zog zog 9,10, yog li tswj cov ntaub so ntswg kev ncaj ncees.Qhov cuam tshuam rau lwm yam khoom ntawm fibrous gels, xws li kev ntxhov siab tsis zoo nyob rau hauv cov lus teb rau shear strain11,12, tseem tsis tau pom.
Cov khoom siv kho tshuab ntawm semi-flexible fibrous hydrogels tau kawm nyob rau hauv uniaxial tension13,14 thiab compression8,15, tab sis lawv txoj kev ywj pheej-induced biaxial compression nyob rau hauv nqaim capillaries lossis hlab tsis tau kawm.Ntawm no peb tshaj tawm cov txiaj ntsig kev sim thiab theoretically tawm tswv yim rau kev coj tus cwj pwm ntawm fibrous hydrogels nyob rau hauv biaxial tuav hauv microfluidic channels.
Fibrin microgels nrog ntau qhov sib piv ntawm fibrinogen thiab thrombin concentrations thiab D0 txoj kab uas hla xws li 150 txog 220 µm tau tsim los siv txoj hauv kev microfluidic (Cov duab ntxiv 1).Ntawm daim duab.1a qhia cov duab ntawm fluorochrome lo lo rau microgels tau siv confocal fluorescence microscopy (CFM).Cov microgels yog spherical, muaj ib tug polydispersity tsawg tshaj li 5%, thiab yog ib yam nyob rau hauv cov qauv nyob rau hauv cov nplais tshuaj ntsuam xyuas los ntawm CFM (Cov ntaub ntawv ntxiv thiab tsos S1 thiab S2).Qhov nruab nrab qhov pore loj ntawm microgels (txiav txim siab los ntawm kev ntsuas Darcy permeability16) txo los ntawm 2280 txog 60 nm, cov ntsiab lus fibrin tau nce los ntawm 5.25 mus rau 37.9 mg / mL, thiab thrombin concentration txo los ntawm 2.56 txog 0.27 units / mL, feem.(Cov ntaub ntawv ntxiv).Rice.2), 3 thiab ntxiv rooj 1).Qhov sib thooj ntawm cov microgel nce ntawm 0.85 mus rau 3.6 kPa (Ntxiv daim duab 4).Raws li cov piv txwv ntawm cov gels tsim los ntawm cov saw hloov tau yooj yim, agarose microgels ntawm ntau yam tawv tawv yog siv.
Fluorescence microscopy duab ntawm fluorescein isothiocyanate (FITC) sau npe PM tshem tawm hauv TBS.Qhov ntsuas bar yog 500 µm.b SEM cov duab ntawm SM (sab saum toj) thiab RM (hauv qab).Scale bar 500nm.c Schematic daim duab ntawm ib tug microfluidic channel muaj xws li ib tug loj channel (inch dl) thiab ib tug nqaim cone-shaped cheeb tsam nrog ib tug nkag lub kaum sab xis ntawm 15 ° thiab ib txoj kab uas hla ntawm dc = 65 µm.d Sab laug mus rau sab xis: Optical microscope dluab ntawm RM (inch D0) nyob rau hauv loj raws, conical cheeb tsam thiab constriction (limiting gel ntev Dz).Qhov ntsuas bar yog 100 µm.e, f TEM dluab ntawm undeformed RM (e) thiab ib tug occluded RM (f), tsau rau ib teev nrog constriction 1/λr = 2.7, ua raws li los ntawm kev tso tawm thiab fixation ntawm 5% ntawm cov loj.Glutaraldehyde hauv TBS.Txoj kab uas hla ntawm lub undeformed CO yog 176 μm.Qhov ntsuas bar yog 100 nm.
Peb tsom mus rau fibrin microgels nrog hardness ntawm 0.85, 1.87 thiab 3.6 kPa (tom qab no hu ua mos microgels (SM), nruab nrab nyuaj microgels (MM) thiab nyuaj microgels (RM), feem).Qhov ntau ntawm fibrin gel txhav yog tib qhov kev txiav txim ntawm qhov loj ntawm cov ntshav txhaws18,19 thiab yog li cov fibrin gels kawm hauv peb txoj haujlwm yog ncaj qha ntsig txog cov kab mob lom neeg tiag tiag.Ntawm daim duab.1b qhia cov duab sab saum toj thiab hauv qab ntawm SM thiab RM cov qauv tau siv lub tshuab ntsuas hluav taws xob (SEM), feem.Piv rau RM cov qauv, SM tes hauj lwm yog tsim los ntawm cov fibers thicker thiab tsawg ceg cov ntsiab lus, raws li cov ntaub ntawv ua ntej 20, 21 (Ntxiv daim duab 5).Qhov sib txawv ntawm cov qauv ntawm hydrogel cuam tshuam nrog cov qauv ntawm nws cov khoom: permeability ntawm cov gel txo nrog txo qhov pore loj los ntawm SM mus rau MM thiab RM (Cov Lus Qhia Ntxiv 1), thiab qhov tawv ntawm cov gel rov qab.Tsis muaj kev hloov pauv hauv cov qauv microgel tom qab khaws cia ntawm 4 ° C rau 30 hnub (Cov duab ntxiv 6).
Ntawm daim duab.1c qhia ib daim duab ntawm lub microfluidic channel nrog lub voj voog hla ntu uas muaj (los ntawm sab laug mus rau sab xis): ib txoj kab loj nrog txoj kab uas hla dl nyob rau hauv uas lub microgel tseem undeformed, lub khob hliav qab seem nrog ib tug nqaim inch dc < D0, cone -zoo li tus seem thiab cov kab loj loj nrog lub cheeb dl (Ntxiv daim duab 7).Hauv kev sim ib txwm, microgels tau txhaj rau hauv cov kab hluav taws xob microfluidic ntawm qhov zoo siab poob ΔP ntawm 0.2–16 kPa (Cov Lus Qhia Ntxiv 8).Qhov siab siab no sib raug rau cov ntshav siab tseem ceeb (120 mm Hg = 16 kPa) 22.Ntawm daim duab.1d (los ntawm sab laug mus rau sab xis) qhia cov duab sawv cev ntawm RM hauv cov channel loj, thaj chaw conical thiab constrictions.Lub zog thiab cov duab ntawm microgel tau sau tseg thiab tshuaj xyuas siv MATLAB program.Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias nyob rau hauv cov cheeb tsam tapering thiab constrictions, cov microgels nyob rau hauv conformal kev sib cuag nrog cov phab ntsa ntawm lub microchannels (Ntxiv daim duab 8).Qhov degree ntawm radial retention ntawm microgel ntawm nqaim D0 / dc = 1 / λr yog nyob rau hauv thaj tsam 2.4 ≤ 1 / λr ≤ 4.2, qhov twg 1 / λr yog qhov sib piv.Lub microgel mus los ntawm shrinkage thaum ΔP > ΔPtr, qhov twg ΔPtr yog qhov sib txawv ntawm qhov sib txawv.Qhov ntev thiab qhov loj ntawm qhov pores ntawm biaxially constrained microgels yog txiav txim los ntawm lawv lub xeev equilibrium, vim nws yog ib qho tseem ceeb heev uas yuav tsum tau coj mus rau hauv tus account lub viscoelasticity ntawm gels nyob rau hauv biological systems.Lub sij hawm sib npaug rau agarose thiab fibrin microgels yog 10 min thiab 30 min, raws li.Tom qab lub sijhawm no, cov microgels txwv tsis pub mus txog lawv txoj haujlwm ruaj khov thiab cov duab, uas tau ntes tau siv lub koob yees duab ceev thiab tshuaj xyuas siv MATLAB.
Ntawm daim duab.1e, 1f qhia kis tau tus mob electron microscopy (TEM) dluab ntawm undeformed thiab biaxially txwv RM qauv.Tom qab RM compression, microgel pore qhov loj me me txo qis thiab lawv cov duab los ua anisotropic nrog qhov me me nyob rau hauv cov kev taw qhia ntawm compression, uas yog raws li ib tug ua ntej daim ntawv qhia 23.
Biaxial compression thaum lub sij hawm contraction ua rau lub microgel elongate nyob rau hauv ib tug unlimited kev taw qhia nrog ib tug coefficient λz = \({D}_{{{{{{{\rm{z}}}}}}}}}}}/\({D }_{ 0}\), qhov twg \({D}_{{{(\rm{z}}}}}}}}\) yog qhov ntev ntawm lub kaw microgel daim duab 2a qhia qhov kev hloov hauv λzvs .1/ λr Rau cov fibrin thiab agarose microgels xav tsis thoob, nyob rau hauv muaj zog compression ntawm 2.4 ≤ 1 / λr ≤ 4.2, fibrin microgels qhia ib tug negligible elongation ntawm 1.12 +/- 0.03 λz, uas tsuas yog me ntsis cuam tshuam los ntawm tus nqi ntawm 1/λr. txwv agarose microgels, uas tau pom txawm tias tsis muaj zog compression 1 / λr = 2.6 rau qhov loj elongation λz = 1.3.
Agarose microgel thwmsim nrog txawv elastic moduli (2.6 kPa, ntsuab qhib pob zeb diamond; 8.3 kPa, xim av qhib lub voj voog; 12.5 kPa, txiv kab ntxwv qhib square; 20.2 kPa, magenta qhib inverted daim duab peb sab) thiab SM (khoom liab) Hloov nyob rau hauv ntsuas elongation λz ( lub voj voog), MM (khoom dub squares) thiab RM (khoom xiav daim duab peb sab).Cov kab khov kho qhia qhov kev kwv yees kwv yees λz rau agarose (kab ntsuab) thiab fibrin microgels (kab thiab cov cim ntawm tib xim).b, c Sab saum toj vaj huam sib luag: schematic daim duab ntawm lub network chains ntawm agarose (b) thiab fibrin (c) ua ntej (sab laug) thiab tom qab (txoj cai) biaxial compression.Hauv qab: Cov duab sib thooj ua ntej thiab tom qab deformation.X thiab y compression cov lus qhia yog qhia los ntawm magenta thiab xim av xub, ntsig txog.Nyob rau hauv daim duab saum toj no, chains ntawm tes hauj lwm taw qhia nyob rau hauv cov x thiab y cov lus qhia yog qhia nrog cov coj magenta thiab xim av kab, thiab chains oriented nyob rau hauv ib tug arbitrary z kev taw qhia yog sawv cev los ntawm cov kab ntsuab.Nyob rau hauv lub fibrin gel (c), cov kab liab thiab xim av nyob rau hauv x thiab y cov lus qhia khoov ntau tshaj nyob rau hauv lub undeformed lub xeev, thiab cov kab ntsuab nyob rau hauv lub z kev taw qhia khoov thiab stretch.Qhov nro ntawm cov lus qhia ntawm compression thiab nro yog kis los ntawm cov xov nrog cov lus qhia nruab nrab.Nyob rau hauv agarose gels, cov chains nyob rau hauv tag nrho cov lus qhia txiav txim siab osmotic siab, uas ua rau ib tug tseem ceeb pab rau lub deformation ntawm lub gel.d Predicted change in biaxial Poisson's ratio, } } }^{{{{{\rm{eff}}}}}}} =-{{{{{\rm{ln}}}}}}{\lambda }_{ z}/{{{{{{ \rm{ln}}}}}}{\lambda }_{r}\ ), rau equibiaxial compression ntawm agarose (kab ntsuab) thiab fibrin (liab kab) gels.Lub inset qhia txog biaxial deformation ntawm gel.e Translocation siab hloov ΔPtr, normalized rau gel txhav S, yog plotted raws li ib tug muaj nuj nqi ntawm compression piv rau agarose thiab fibrin microgels.Cov cim xim sib haum rau cov xim hauv (a).Cov kab ntsuab thiab liab qhia txog kev sib raug zoo ntawm ΔPtr / S thiab 1 / λr rau agarose thiab fibrin gels, feem.Lub dashed ib feem ntawm kab liab qhia qhov nce hauv ΔPtr nyob rau hauv muaj zog compression vim interfiber kev sib tshuam.
Qhov sib txawv no yog txuam nrog cov txheej txheem sib txawv ntawm kev deformation ntawm fibrin thiab agarose microgel tes hauj lwm, uas muaj xws li saj zawg zog24 thiab rigid25 threads, feem.Biaxial compression ntawm saj zawg zog gels ua rau ib tug txo nyob rau hauv lawv ntim thiab ib tug txuam nrog nce concentration thiab osmotic siab, uas ua rau ib tug elongation ntawm cov gel nyob rau hauv ib tug unlimited kev taw qhia.Qhov kawg elongation ntawm cov gel nyob ntawm qhov sib npaug ntawm qhov nce hauv lub zog tsis pub dawb ntawm cov hlua khi thiab qhov txo qis ntawm lub zog dawb ntawm osmosis vim qhov qis ntawm cov polymer concentration hauv cov gel stretched.Raws li muaj zog biaxial compression, elongation ntawm cov gel nce nrog λz ≈ 0.6 \({{\lambda}_{{{\rm{r}}}}^{-2/3}}\) (saib daim duab 2a hauv nqe lus sib tham 5.3.3).Cov kev hloov pauv ntawm cov saw hlau hloov tau yooj yim thiab cov duab ntawm cov tes hauj lwm sib txuas ua ntej thiab tom qab biaxial tuav tau qhia hauv daim duab.2b ib.
Hauv qhov sib piv, fibrous gels xws li fibrin inherently teb txawv rau biaxial tuav.Cov filaments oriented feem ntau sib npaug rau cov kev taw qhia ntawm compression flex (yog li txo qhov kev ncua deb ntawm kev sib txuas), thaum lub filaments feem ntau yog perpendicular mus rau cov kev taw qhia ntawm compression straighten thiab stretch nyob rau hauv qhov kev txiav txim ntawm elastic quab yuam, ua rau lub gel rau elongate ( Daim duab 1).2c) Cov qauv ntawm qhov tsis zoo ntawm SM, MM thiab RM tau raug txheeb xyuas los ntawm kev txheeb xyuas lawv cov duab SEM thiab CFM (Cov Kev Sib Tham Ntxiv IV thiab Cov Duab Ntxiv 9).Los ntawm kev txiav txim siab elastic modulus (E), txoj kab uas hla (d), qhov ntev profile (R0), qhov nrug ntawm qhov kawg (L0 ≈ R0) thiab lub kaum sab xis hauv nruab nrab (ψ0) ntawm cov strands hauv undeformed fibrin microgels (Table 2) - 4), peb pom tias xov dabtsi yog khoov modulus \({k}_{{{{{{{\rm{b))))))))))))}=\frac{9\pi E{d}^{4} } {4 {\psi } _{0}^{2}{L}_{0}}\) yog tsawg dua nws tensile modulus\({k}_{{{{{{{\rm{s}}}} } } }} }}=E\frac{\pi {d}^{2}{R}_{0}}{4}\), so kb/ks ≈ 0.1 (Table 4).Yog li, nyob rau hauv cov xwm txheej ntawm biaxial gel tuav, fibrin strands yooj yim khoov, tab sis tiv taus ncab.Lub elongation ntawm ib tug filamentous network raug rau biaxial compression yog qhia nyob rau hauv Ntxiv Fig. 17.
Peb tsim cov qauv theoretical affine (Cov Kev Sib Tham Ntxiv Ntu V thiab Cov Duab Ntxiv 10–16) uas qhov elongation ntawm fibrous gel yog txiav txim siab los ntawm lub zos sib npaug ntawm cov elastic rog ua yeeb yam hauv gel thiab kwv yees tias nyob rau hauv lub zog biaxial strain λz - 1 nyob rau hauv kev txwv
Qhov sib npaug (1) qhia tau hais tias txawm nyob rau hauv muaj zog compression (\(\lambda }_{{{\mbox{r))))\,\to \,0\)) muaj me ntsis gel expansion thiab tom qab elongation deformation thaum saturation λz–1 = 0.15 ± 0.05.Qhov kev coj cwj pwm no muaj feem xyuam rau (i) \(\left({k}_{{{{(\rm{b}}}}}}}}})/{k}_{{{{{\rm { s }}}}}}}\right)}^{1/2}\) ≈ 0.15−0.4 and (ii) lub sij hawm hauv square brackets asymptotically approximates \(1{{\mbox{/}}} \sqrt { 3 }\) rau muaj zog biaxial bonds. Nws yog ib qho tseem ceeb kom nco ntsoov tias prefactor \({\left({k}_{(\mbox{b))))/{k}_{(\mbox{ s))))\right)}^{1/ 2 }\) tsis muaj dab tsi cuam tshuam nrog qhov nruj ntawm cov xov E, tab sis tsuas yog txiav txim siab los ntawm qhov sib piv ntawm cov xov d / L0 thiab lub hauv paus kaum ntawm lub arc ψ0, uas zoo ib yam li SM, MM thiab RM (Table Ntxiv 4).
Txhawm rau ntxiv qhov sib txawv ntawm kev ywj pheej-induced strain ntawm saj zawg zog thiab filamentous gels, peb qhia lub biaxial Poisson tus piv \({\nu }_{{{({\rm{b)))))) }{{\ mbox { =}}}\,\mathop{{\lim}}\limits_{{\lambda}_{{{{(\rm{r}}}}}}\to 1}\frac{{\lambda } _{{{{{\rm{z}}}}}}-1}{1-{\lambda }_{{({\rm{r}}}}}}}}, \) piav qhia txog qhov tsis muaj kev taw qhia ntawm gel strain nyob rau hauv cov lus teb rau sib npaug strain nyob rau hauv ob lub radial cov lus qhia, thiab extends qhov no mus rau loj uniform hom \ rm{b }}}}}}}}}^{{{{\rm{eff}}}}}}}} }}=-{{{{{\rm{ln}}}}}} }{\lambda _{z} /{{{(\rm{ln))))))}{\lambda }_{{(\rm{r))))))))))))Ntawm daim duab.2d shows \({{{{{\rm{\nu }}}}}}}}_{{{(\rm{b}}}}}}}^{{{{\rm {eff }}}}}}}}\) rau kev sib txuam biaxial compression ntawm saj zawg zog (xws li agarose) thiab nruj (xws li fibrin) gels (Kev sib tham ntxiv, Tshooj 5.3.4), thiab qhia txog kev sib raug zoo ntawm qhov sib txawv muaj zog hauv cov lus teb rau kev kaw. Rau agarose gels nyob rau hauv cov kev txwv muaj zog {\rm{eff}}}}}}}\) nce mus rau asymptotic tus nqi 2/3, thiab rau fibrin gels nws txo mus rau xoom, txij li thaum lnλz / lnλr → 0, txij li λz nce nrog saturation raws li λr nce.Nco ntsoov tias hauv qhov kev sim, kaw lub voj voog microgels deform inhomogeneously, thiab lawv qhov nruab nrab muaj kev cuam tshuam zoo dua;Txawm li cas los xij, extrapolation rau tus nqi loj ntawm 1 / λr ua rau nws muaj peev xwm los sib piv qhov kev sim nrog txoj kev xav rau cov gels tsis sib xws.
Lwm qhov sib txawv ntawm tus cwj pwm ntawm cov gels hloov tau yooj yim thiab cov gels filamentous tau pom vim tias lawv txav mus los ntawm kev cog lus.Lub translocation siab ΔPtr, normalized rau gel txhav S, nce nrog nce compression (Fig. 2e), tab sis ntawm 2.0 ≤ 1 / λr ≤ 3.5, fibrin microgels pom qhov tseem ceeb ntawm ΔPtr / S down thaum lub sij hawm shrinkage.Kev tuav ntawm agarose microgel ua rau muaj qhov nce hauv osmotic siab, uas ua rau lub zog ntawm cov gel nyob rau hauv qhov kev taw qhia longitudinal raws li cov polymer molecules yog stretched (Fig. 2b, sab laug) thiab ib tug nce nyob rau hauv translocation siab los ntawm ΔPtr / S ~ ( 1/lr)14/317.Ntawm qhov tsis sib xws, cov duab ntawm cov fibrin microgels kaw yog txiav txim siab los ntawm lub zog sib npaug ntawm cov xov ntawm radial compression thiab longitudinal nro, uas ua rau lub siab tshaj plaws longitudinal deformation λz ~ \ (\ sqrt {{k}_{{ { { { { \rm{b)))))))} /{k}_{{{{{{\rm{s}}}}}}}}}\).Rau 1/λr ≫ 1, qhov kev hloov pauv hauv siab yog ntsuas raws li 1 }{{{(({\rm{ln)))))))\left({{\lambda }}_{{{{{\rm {r} }}}}}}}}^{{-} 1} \right)\) (Kev Sib Tham Ntxiv, Tshooj 5.4), raws li qhia los ntawm cov kab liab liab hauv daim duab 2e.Yog li, ΔPtr tsis muaj kev txwv tsawg dua li hauv agarose gels.Rau compressions nrog 1 / λr> 3.5, ib qho tseem ceeb nce nyob rau hauv lub ntim feem ntawm filaments thiab kev sib cuam tshuam ntawm cov nyob sib ze filaments txwv ntxiv deformation ntawm gel thiab ua rau deviations ntawm kev sim tau los ntawm kev kwv yees (liab dotted kab hauv daim duab 2e).Peb xaus lus tias rau tib 1/λr thiab Δ\({P}_{{{{{{\rm{tr}}}}}}}}}}_{{{\rm{fibrin}}} )) } }}}\) < ΔP < Δ\({P}_{{{{{{{\rm{tr))))))}}}_{{{\rm{agarose}} }} } } } }}\) agarose gel yuav raug ntes los ntawm microchannel, thiab cov fibrin gel nrog tib lub zog yuav dhau los ntawm nws.For ΔP < Δ\({P}_{{{{{\rm{tr)))))))))))))))))))))))))) ), Ob Ob leeg gels yuav thaiv cov channel, tab sis cov fibrin gel yuav thawb tob dua thiab compress zoo dua, thaiv cov kua dej ntws zoo dua.Cov txiaj ntsig tau pom hauv daim duab 2 qhia tau tias cov gel fibrous tuaj yeem ua haujlwm zoo los txo cov ntshav los yog inhibit cov ntshav rau cov qog.
Ntawm qhov tod tes, fibrin tsim cov hlab ntsha uas ua rau thromboembolism, ib qho kev mob uas muaj cov kab mob thrombus occludes lub nkoj ntawm ΔP < ΔPtr, xws li hauv qee hom ischemic stroke (Fig. 3a).Qhov tsis muaj zog txwv-induced elongation ntawm fibrin microgels ua rau muaj zog ntxiv ntawm fibrin concentration ntawm C / C fibrinogen piv rau cov saw hloov tau yooj yim, qhov twg C thiab C fibrinogen raug txwv thiab undeformed microgels, feem.Polymer concentration hauv gel.Daim duab 3b qhia tau hais tias fibrinogen C/C hauv SM, MM, thiab RM tau nce ntau tshaj xya npaug ntawm 1/λr ≈ 4.0, uas tau tsav los ntawm kev txwv thiab lub cev qhuav dej (Ntxiv daim duab 16).
Schematic illustration ntawm occlusion ntawm nruab nrab cerebral hlab ntsha nyob rau hauv lub hlwb.b Kev txwv-kho cov txheeb ze nce hauv fibrin concentration hauv obstructive SM (khoom liab lub voj voog), MM (khoom dub squares), thiab RM (khoom xiav daim duab peb sab).c Kev sim tsim siv los kawm txog qhov sib cais ntawm kev txwv fibrin gels.Ib qho kev daws teeb meem ntawm fluorescently sau npe tPA hauv TBS tau txhaj ntawm tus nqi ntws ntawm 5.6 × 107 µm3 / s thiab ib qho kev poob siab ntxiv ntawm 0.7 Pa rau cov channel nyob rau ntawm qhov ntev ntawm lub ntsiab microchannel.d Pooled multichannel microscopic duab ntawm obstructive MM (D0 = 200 µm) ntawm Xf = 28 µm, ΔP = 700 Pa thiab thaum sib cais.Vertical dotted kab qhia thawj txoj hauj lwm ntawm lub posterior thiab anterior ntug ntawm MM ntawm tlys = 0. Ntsuab thiab liab xim sib haum rau FITC-dextran (70 kDa) thiab tPA sau nrog AlexaFluor633, raws li.e Lub Sijhawm sib txawv ntawm qhov sib txawv ntawm qhov sib txawv ntawm RMs nrog D0 ntawm 174 µm (xiav qhib daim duab peb sab), 199 µm (xiav daim duab peb sab), thiab 218 µm (xiav daim duab peb sab), feem, nyob rau hauv lub conical microchannel nrog Xf = 28 ± 1 µm.cov seem muaj ΔP 1200, 1800, thiab 3000 Pa, feem, thiab Q = 1860 ± 70 µm3 / s.Lub inset qhia RM (D0 = 218 µm) ntsaws lub microchannel.f Lub sij hawm variation ntawm tus txheeb ze ntim ntawm SM, MM los yog RM muab tso rau ntawm Xf = 32 ± 12 µm, ntawm ΔP 400, 750 thiab 1800 Pa thiab ΔP 12300 Pa thiab Q 12300 nyob rau hauv cheeb tsam conical ntawm lub microchannel, raws li 2400 thiab µ 1860 /s.Xf sawv cev rau pem hauv ntej txoj hauj lwm ntawm microgel thiab txiav txim siab nws nyob deb ntawm qhov pib ntawm shrinkage.V (tlys) thiab V0 yog qhov ntim ib ntus ntawm cov lysed microgel thiab qhov ntim ntawm cov microgel tsis muaj kev cuam tshuam, feem.Cov cim xim sib haum rau cov xim hauv b.Cov xub dub ntawm e, f sib raug rau lub sijhawm kawg ntawm lub sijhawm ua ntej qhov kev tso cai ntawm microgels los ntawm microchannel.Qhov ntsuas bar hauv d, e yog 100 µm.
Txhawm rau tshawb xyuas cov txiaj ntsig ntawm kev txwv ntawm kev txo cov kua dej hla ntawm obstructive fibrin gels, peb tau kawm cov lysis ntawm SM, MM, thiab RM infiltrated nrog thrombolytic tus neeg sawv cev cov ntaub so ntswg plasminogen activator (tPA).Daim duab 3c qhia txog kev sim tsim siv rau kev sim lysis. Ntawm ΔP = 700 Pa (<ΔPtr) thiab tus nqi ntws, Q = 2400 μm3 / s, ntawm Tris-buffered saline (TBS) tov nrog 0.1 mg / mL ntawm (fluorescein isothiocyanate) FITC-Dextran, microgel occluded lub tapered microchannel. cheeb tsam. Ntawm ΔP = 700 Pa (<ΔPtr) thiab tus nqi ntws, Q = 2400 μm3 / s, ntawm Tris-buffered saline (TBS) tov nrog 0.1 mg / mL ntawm (fluorescein isothiocyanate) FITC-Dextran, microgel occluded lub tapered microchannel. cheeb tsam. При ΔP = 700 Па (<ΔPtr) и скорости потока, Q = 2400 мкм3/с, трис-буферного солевого раствора (TBS), смруствора (TBS), смешошанго еинизотиоцианата) FITC-декстрана, микрогель перекрывал сужающийся микроканал. Ntawm ΔP = 700 Pa (<ΔPtr) thiab tus nqi ntws, Q = 2400 µm3 / s, ntawm Tris buffered saline (TBS) tov nrog 0.1 mg / mL (fluorescein isothiocyanate) FITC-dextran, microgel occluded lub converging microchannel.cheeb tsam.在ΔP = 700 Pa (<ΔPtr) 和流速Q = 2400 μm3/s 的Tris 缓冲盐水(TBS) 与0.1 mg/mL的（异硫氰酸荧具素）凝胶堵塞了锥形微通道地区.在ΔP = 700 Pa (<ΔPtr) 和流速Q = 2400 μm3/s了锥形微通道地区. Микрогели закупориваются при смешивании трис-буферного солевого раствора (TBS) с 0.1 мог/мл (флуортрерного солевого раствора (TBS) с 0.1 мг/мл (флуортризес) на при ΔP = 700 Па (<ΔPtr) и скорости потока Q = 2400 мкм3/с Конические области микроканалов. Microgels ntsaws thaum Tris buffered saline (TBS) yog tov nrog 0.1mg/mL (fluorescein isothiocyanate) FITC-dextran ntawm ΔP = 700 Pa (<ΔPtr) thiab txaus tus nqi Q = 2400 µm3/s Conical cheeb tsam ntawm microchannels.Txoj hauj lwm pem hauv ntej Xf ntawm microgel txiav txim siab nws qhov deb ntawm qhov pib shrinkage point X0.Txhawm rau induce lysis, ib qho kev daws teeb meem ntawm fluorescently sau npe tPA hauv TBS tau txhaj los ntawm cov channel nyob hauv orthogonally mus rau qhov ntev ntawm lub ntsiab microchannel.
Thaum cov tshuaj tPA mus txog qhov occlusal MM, lub posterior ntug ntawm microgel los ua qhov muag plooj, qhia tias fibrin cleavage tau pib thaum lub sij hawm tlys = 0 (Fig. 3d thiab Supplementary Fig. 18).Thaum lub sij hawm fibrinolysis, dye-labeled tPA accumulates nyob rau hauv lub MM thiab khi rau fibrin strands, uas ua rau ib tug maj mam nce nyob rau hauv cov xim liab ntawm cov microgels.Ntawm tlys = 60 min, MM sib cog lus vim qhov tawg ntawm nws lub nraub qaum, thiab txoj hauj lwm ntawm nws cov ntug Xf hloov me ntsis.Tom qab 160 min, qhov kev cog lus ruaj khov MM txuas ntxiv mus rau daim ntawv cog lus, thiab ntawm tlys = 161 min, nws tau txais kev cog lus, yog li rov ua kom cov dej ntws los ntawm microchannel (Daim duab 3d thiab ntxiv daim duab 18, sab xis).
Ntawm daim duab.3e qhia tau hais tias lysis-mediated lub sij hawm-dependent txo nyob rau hauv ntim V (tlys) normalized rau thawj ntim V0 ntawm txawv me me fibrin microgels.CO nrog D0 174, 199, lossis 218 µm tau muab tso rau hauv microchannel nrog ΔP 1200, 1800, lossis 3000 Pa, feem, thiab Q = 1860 ± 70 µm3 / s los thaiv cov microchannel (Fig. 3e, inset).khoom noj khoom haus.Cov microgels maj mam txo kom txog thaum lawv me me kom dhau los ntawm cov channel.Ib qho kev txo qis hauv qhov tseem ceeb ntawm CO nrog lub taub loj dua pib xav tau lub sijhawm lysis ntev dua.Vim qhov zoo sib xws ntws los ntawm qhov sib txawv ntawm RMs, cleavage tshwm sim ntawm tib tus nqi, uas ua rau kev zom cov feem me me ntawm RMs loj dua thiab lawv qhov kev hloov pauv qeeb.Ntawm daim duab.3f qhia qhov txheeb ze txo qis hauv V (tlys) / V0 vim kev sib cais rau SM, MM, thiab RM ntawm D0 = 197 ± 3 µm plotted ua haujlwm ntawm tlys.Rau SM, MM thiab RM, tso txhua lub microgel hauv microchannel nrog ΔP 400, 750 lossis 1800 Pa thiab Q 12300, 2400 lossis 1860 µm3 / s, raws li.Txawm hais tias lub siab siv rau SM yog 4.5 npaug qis dua li ntawm RM, qhov ntws los ntawm SM yog ntau tshaj li rau lub sij hawm muaj zog vim qhov siab dua permeability ntawm SM, thiab lub shrinkage ntawm microgel poob ntawm SM mus rau MM thiab RM. .Piv txwv li, ntawm tlys = 78 min, SM feem ntau yaj thiab tshem tawm, thaum MM thiab PM txuas ntxiv mus kaw cov microchannels, txawm tias khaws cia tsuas yog 16% thiab 20% ntawm lawv qhov qub ntim, feem.Cov txiaj ntsig no qhia txog qhov tseem ceeb ntawm convection-mediated lysis ntawm constricted fibrous gels thiab cuam tshuam nrog cov lus ceeb toom ntawm kev zom sai ntawm cov hlab ntshav nrog cov ntsiab lus fibrin qis.
Yog li, peb txoj haujlwm ua kom pom kev sim thiab theoretically lub tshuab uas filamentous gels teb rau biaxial confinement.Tus cwj pwm ntawm fibrous gels nyob rau hauv ib qho chaw txwv yog txiav txim siab los ntawm qhov muaj zog asymmetry ntawm lub zog ntawm lub zog ntawm cov filaments (mos hauv compression thiab nyuaj hauv nro) thiab tsuas yog los ntawm qhov sib piv thiab curvature ntawm cov filaments.Cov tshuaj tiv thaiv no ua rau tsawg kawg elongation ntawm fibrous gels muaj nyob rau hauv nqaim capillaries, lawv biaxial Poisson tus piv txo nrog nce compression thiab tsawg lub teeb me ntsis.
Txij li thaum biaxial ntim ntawm mos deformable hais yog siv nyob rau hauv ib tug ntau yam ntawm technologies, peb cov txiaj ntsig txhawb kev tsim cov ntaub ntawv fiber ntau tshiab.Hauv particular, biaxial tuav ntawm filamentous gels nyob rau hauv nqaim capillaries los yog hlab ua rau lawv muaj zog compaction thiab ib tug ntse txo nyob rau hauv permeability.Qhov muaj zog inhibition ntawm cov kua dej ntws los ntawm occlusive fibrous gels muaj qhov zoo thaum siv cov ntsaws ruaj ruaj los tiv thaiv los ntshav los yog txo cov ntshav mus rau malignancies33,34,35.Ntawm qhov tod tes, qhov txo qis hauv cov kua dej ntws los ntawm occlusal fibrin gel, yog li inhibiting convective-mediated thrombus lysis, muab ib qho kev qhia ntawm qeeb lysis ntawm occlusal clots [27, 36, 37].Peb cov qauv qauv yog thawj kauj ruam ntawm kev nkag siab txog qhov cuam tshuam ntawm cov lus teb ntawm cov khoom siv fiber ntau biopolymer hydrogels rau biaxial tuav.Kev koom ua ke cov qe ntshav los yog platelets rau hauv obstructive fibrin gels yuav cuam tshuam rau lawv tus cwj pwm txwv 38 thiab yuav yog kauj ruam tom ntej hauv kev nthuav tawm tus cwj pwm ntawm cov txheej txheem lom neeg ntau dua.
Reagents siv los npaj fibrin microgels thiab fabricate MF li tau piav qhia nyob rau hauv Cov Ntaub Ntawv Ntxiv (Cov Txheej Txheem Ntxiv Tshooj 2 thiab 4).Fibrin microgels tau npaj los ntawm emulsifying ib qho kev sib xyaw ntawm fibrinogen, Tris tsis thiab thrombin nyob rau hauv ib tug txaus tsom MF ntaus ntawv, ua raws li los ntawm droplet gelation.Bovine fibrinogen tov (60 mg / ml hauv TBS), Tris buffer thiab bovine thrombin tov (5 U / ml hauv 10 mM CaCl2 tov) tau muab siv ob lub twj tso kua mis tswj tus kheej (PhD 200 Harvard Apparatus PHD 2000 Syring Pump).los thaiv MF, USA).F-roj txuas ntxiv theem uas muaj 1 wt.% thaiv copolymer PFPE-P(EO-PO)-PFPE, tau nkag mus rau hauv MF chav tsev siv lub twj tso kua mis thib peb.Droplets tsim nyob rau hauv MF ntaus ntawv yog sau nyob rau hauv ib tug 15 ml centrifuge raj uas muaj F-roj.Muab cov hlab tso rau hauv ib da dej ntawm 37 ° C rau 1 h kom tiav fibrin gelation.FITC sau npe fibrin microgels tau npaj los ntawm kev sib xyaw bovine fibrinogen thiab FITC sau npe tib neeg fibrinogen hauv 33: 1 qhov hnyav piv, feem.Cov txheej txheem yog tib yam li kev npaj ntawm fibrin microgels.
Hloov cov microgels los ntawm cov roj F mus rau TBS los ntawm centrifuging qhov dispersion ntawm 185 g rau 2 min.Lub precipitated microgels tau dispersed nyob rau hauv cov roj F tov nrog 20 wt.% perfluorooctyl cawv, ces dispersed nyob rau hauv hexane muaj 0.5 wt.% Span 80, hexane, 0.1 wt.% Triton X nyob rau hauv dej thiab TBS.Thaum kawg, cov microgels tau tawg mus rau hauv TBS uas muaj 0.01 wt% Tween 20 thiab khaws cia ntawm 4 ° C rau kwv yees li 1-2 lub lis piam ua ntej kev sim.
Kev tsim cov khoom siv MF tau piav qhia nyob rau hauv Cov Lus Qhia Ntxiv (Cov Txheej Txheem Ntxiv Tshooj 5).Hauv kev sim ib txwm, qhov txiaj ntsig zoo ntawm ΔP yog txiav txim siab los ntawm tus txheeb ze qhov siab ntawm cov reservoirs txuas ua ntej thiab tom qab MF ntaus ntawv rau kev qhia microgels nrog txoj kab uas hla ntawm 150 < D0 < 270 µm rau hauv microchannels.Qhov loj me me ntawm microgels tau txiav txim siab los ntawm kev pom lawv hauv macrochannel.Lub microgel nres nyob rau hauv ib qho chaw conical ntawm qhov nkag mus rau constriction.Thaum lub ntsis ntawm lub anterior microgel tseem tsis hloov pauv rau 2 min, siv MATLAB qhov kev pab cuam los txiav txim qhov chaw ntawm microgel raws li x-axis.Nrog kev nce qib hauv ΔP, lub microgel txav mus raws thaj tsam ntawm lub npoo kom txog thaum nws nkag mus rau hauv qhov chaw.Thaum lub microgel tau muab tso rau tag nrho thiab compressed, ΔP sai poob mus rau xoom, ntsuas cov dej theem ntawm cov reservoirs, thiab kaw microgel tseem nyob twj ywm hauv compression.Qhov ntev ntawm obstructive microgel tau ntsuas 30 min tom qab qhov kev txwv tsis pub dhau.
Thaum lub sij hawm kev sim fibrinolysis, cov kev daws teeb meem ntawm t-PA thiab FITC-labeled dextran nkag mus rau blocked microgels.Kev khiav ntawm txhua cov kua tau saib xyuas siv ib qho channel fluorescence imaging.TAP sau nrog AlexaFluor 633 txuas rau fibrin fibers thiab khaws cia hauv compressed fibrin microgels (TRITC channel hauv Supplementary Fig. 18).Cov tshuaj dextran sau nrog FITC txav tsis muaj qhov sib txuam hauv microgel.
Cov ntaub ntawv txhawb nqa cov txiaj ntsig ntawm txoj kev tshawb fawb no muaj los ntawm cov kws sau ntawv raws li kev thov.Raw SEM dluab ntawm fibrin gels, raw TEM dluab ntawm fibrin gels ua ntej thiab tom qab inoculation, thiab lub ntsiab input ntaub ntawv rau daim duab 1 thiab 2. 2 thiab 3 yog muab nyob rau hauv cov ntaub ntawv raw cov ntaub ntawv.Kab lus no muab cov ntaub ntawv qub.
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Post lub sij hawm: Feb-23-2023