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Kudzikiswa kwemafibrous hydrogels kutetepa capillaries kwakakosha zvikuru mubiological and biomedical system.Tension uye uniaxial compression yefibrous hydrogels yakadzidzwa zvakanyanya, asi mhinduro yavo kune biaxial kuchengetwa mumacapillaries inoramba isina kuongororwa.Pano, isu tinoratidza experimentally uye theoretically kuti filamentous gels anopindura qualitatively zvakasiyana kumanikidzira pane flexible cheni gels nokuda asymmetry ari mechanical ehupfumi ari constituent filaments, izvo zvinyoro mukutsikirira uye kuoma mukukakavadzana.Pasi pekuchengetedzwa kwakasimba, iyo fibrous gel inoratidzira kurebesa kushoma uye kuderera kweasymptotic muyero ye biaxial Poisson kusvika zero, zvichikonzera kusimba kwegel compact uye kushomeka kwemvura kupenya kuburikidza nejeri.Mhedzisiro iyi inoratidza kuramba kweyakatambanudzwa occlusive thrombi kune lysis nevarapi vamiririri uye inokurudzira kuvandudzwa kweiyo inoshanda endovascular embolization kubva kune fibrous gels kumisa vascular kubuda ropa kana kurambidza kupihwa kweropa kwemamota.
Fibrous network ndiwo akakosha ekumisikidza uye anoshanda ekuvaka zvivharo zvematishu uye masero mapenyu.Actin chikamu chikuru che cytoskeleton1;fibrin chinhu chakakosha mukupora maronda uye thrombus formation2, uye collagen, elastin uye fibronectin zvikamu zve extracellular matrix mumhuka3.Manetiweki akadzoserwa efibrous biopolymers ave zvinhu zvine maapplication akafara muinjiniya yetishu4.
Filamentous network inomiririra kirasi yakaparadzana yebiological soft matter ine mechanic properties iyo yakasiyana neinochinjika molecular network5.Zvimwe zvezvinhu izvi zvakashanduka munguva yekushanduka-shanduka kudzora mhinduro yebiological matter kune deformation6.Semuyenzaniso, mafibrous network anoratidza linear elasticity padiki strains7,8 nepo pahombe strains vanoratidza kuwedzera kuomarara9,10, nekudaro vachichengeta kuperera kwetishu.Mhedzisiro yemamwe ma mechanic properties ye fibrous gels, senge isina kunaka yakajairika kusagadzikana mukupindura shear strain11,12, haisati yawanikwa.
Iyo mechanical properties ye semi-flexible fibrous hydrogels yakadzidzwa pasi pe uniaxial tension13,14 uye compression8,15, asi rusununguko-induced biaxial compression mumapilari akamanikana kana machubhu haana kudzidza.Pano isu tinoshuma mhedzisiro yekuyedza uye ne theoretically tinokurudzira maitiro eiyo fibrous hydrogels pasi pe biaxial retention mumakrofluidic chiteshi.
Fibrin microgels ine zviyero zvakasiyana-siyana zvefibrinogen uye thrombin concentrations uye D0 dhayamita kubva ku150 kusvika ku220 µm yakagadzirwa uchishandisa nzira ye microfluidic (Supplementary Figure 1).Pamusoro pemuonde.1a inoratidza mifananidzo yefluorochrome yakanyorwa mamicrogel akawanikwa achishandisa confocal fluorescence microscopy (CFM).Iwo ma microgel ane denderedzwa, ane polydispersity isingasviki 5%, uye akafanana muchimiro pachiyero chakaongororwa neCFM (Supplementary Information uye Mafirimu S1 uye S2).Ivhareji yepore ye microgels (yakatemerwa nekuyera Darcy permeability16) yakaderera kubva ku2280 kusvika ku60 nm, zvinyorwa zvefibrin zvakawedzera kubva ku5.25 kusvika ku37.9 mg / mL, uye thrombin concentration yakaderera kubva ku2.56 kusvika ku0.27 units / mL, maererano.(Ruzivo Rwokuwedzera).Mupunga.2), 3 uye tafura yekuwedzera 1).Kuoma kwakafanana kweiyo microgel kunowedzera kubva ku0.85 kusvika ku3.6 kPa (Supplementary Fig. 4).Semienzaniso yemageji akaumbwa kubva kumaketani anochinjika, agarose microgels eakasiyana kuomarara anoshandiswa.
Fluorescence microscopy mufananidzo wefluorescein isothiocyanate (FITC) wakanyorwa kuti PM wakamiswa muTBS.Chiyero chebhawa i500 µm.b SEM mifananidzo yeSM (yepamusoro) uye RM (pasi).Scale bar 500 nm.c Schematic diagram ye microfluidic channel ine mugero hombe (diameter dl) nenzvimbo yakatetepa yakaita sekoni ine kona yekupinda α ye15° uye dhayamita yedc = 65 µm.d Kuruboshwe kuenda kurudyi: Optical microscope mifananidzo yeRM (dhayamita D0) mumatanho mahombe, conical zone uye constriction (inoderedza kureba kwegel Dz).Chiyero chebhawa i100 µm.e, f TEM mifananidzo ye RM isina kuchinjwa (e) uye yakavharwa RM (f), yakagadziriswa kweawa imwe ine constriction 1/λr = 2.7, inoteverwa nekusunungurwa uye kugadziriswa kwe5% yehuwandu.glutaraldehyde muTBS.Iyo dhayamita yeiyo isina kuumbwa CO i176 μm.Scale bar ndeye 100 nm.
Isu takatarisa kune fibrin microgels nekuomarara kwe0.85, 1.87 uye 3.6 kPa (inozonzi nyoro microgels (SM), yepakati hard microgels (MM) uye yakaoma microgels (RM), zvichiteerana).Urwu rudzi rwefibrin gel stiffness ndeyekurongeka kwakafanana nekwekugwamba kweropa18,19 uye nokudaro majelisi efibrin akadzidzwa mubasa redu anoenderana zvakananga nechaiyo biological systems.Pamusoro pemuonde.1b inoratidza mifananidzo yepamusoro neyepasi yeSM neRM zvimiro zvakawanikwa uchishandisa scanning electron maikorosikopu (SEM), zvichiteerana.Kuenzaniswa neRM zvivako, SM network inoumbwa nemafuta akareba uye mashoma ebazi, inopindirana nemishumo yapfuura 20, 21 (Supplementary Fig. 5).Musiyano muchimiro cheiyo hydrogel inopindirana nemaitiro ezvivakwa zvayo: iyo permeability yegel inoderera nekuderera kwepore saizi kubva SM kusvika MM uye RM (Supplementary Tafura 1), uye kuoma kwegel kunodzosera.Hapana kuchinja mukugadzirwa kwe microgel kwakaonekwa mushure mekuchengetedza pa 4 ° C kwemazuva makumi matatu (Supplementary Fig. 6).
Pamusoro pemuonde.1c inoratidza dhayagiramu ye microfluidic chiteshi ine denderedzwa muchinjiko chikamu chine (kubva kuruboshwe kuenda kurudyi): chiteshi chikuru chine dhayamita dl umo microgel inoramba isina kushanduka, chikamu chakaita koni ine dhayamita dc
Pamusoro pemuonde.1e, 1f inoratidza kutapurirana maelectron microscopy (TEM) mifananidzo yezvimiro zvisina kushanduka uye biaxially zvishoma zveRM.Mushure mekumanikidzwa kweRM, iyo microgel pore saizi yakadzikira zvakanyanya uye chimiro chavo chakava anisotropic nemadiki madiki munzira yekumanikidza, iyo inopindirana nemushumo wekare 23.
Biaxial compression panguva yekumanikana inoita kuti microgel irebe munzira isina muganho ine coefficient λz = \({D}_{{{{{{\rm{z}}}}}}}/\({D }_ { 0}\) , apo \({D}_{{{({({\rm{z}}}}}}}}\) pane kureba kwe microgel yakavharwa Mufananidzo 2a unoratidza shanduko mu λzvs .1/ λr Sezvineiwo, pasi pekudzvanya kwakasimba kwe2.4 ≤ 1/λr ≤ 4.2, fibrin microgels inoratidza kurebesa kusingatarisike kwe1.12 +/- 0.03 λz, inongokanganiswa zvishoma nekukosha kwe1/λr. mashoma agarose microgels, ayo anocherechedzwa kunyangwe pakutsikirirwa kusina simba 1/λr = 2.6 kusvika pakurebesa kukuru λz = 1.3.
Agarose microgel inoedza neakasiyana elastic moduli (2.6 kPa, girinhi yakavhurika dhaimani; 8.3 kPa, brown yakavhurika denderedzwa; 12.5 kPa, orenji yakavhurika sikweya; 20.2 kPa, magenta akavhurika inverted triangle) uye SM (yakasimba tsvuku) Shandura mukuyera kureba λz ( madenderedzwa), MM (yakasimba dema mativi) uye RM (yakasimba yebhuruu katatu).Mitsetse yakasimba inoratidza zvakafanotaurwa ne theoretically λz ye agarose (green line) uye fibrin microgels (mitsetse nezviratidzo zveruvara rumwechete).b.Pazasi: Chimiro chetiweki inoenderana isati yasvika uye mushure mekushandurwa.Iyo x uye y compression nzira inoratidzwa nemagenta uye brown miseve, zvichiteerana.Mumufananidzo uri pamusoro, cheni dzemambure akatariswa mune aya x uye y mafambiro anoratidzwa aine inoenderana magenta uye mitsara yebrown, uye cheni dzakanangidzirwa munzira yekupokana z inomiririrwa nemitsara yegirinhi.Mune fibrin gel (c), mitsara yepepuru neshava mu x uye y nzira inokotama kupfuura mune isina kurongeka, uye mitsetse yegirini mu z direction inokotama nekutambanudza.Makakatanwa ari pakati pemakwara ekudzvanyirira uye kudhonzerana kunofambiswa kuburikidza neshinda dzine madirections epakati.Mune agarose gels, maketani kumativi ose anotarisa osmotic pressure, iyo inobatsira zvikuru pakuparara kwejeri.d Kufanofungidzira shanduko muchiyero chebiaxial Poisson, } }^{{{{{\rm{eff}}}}}}}} =-{{{{\rm{ln}}}}}}{\lambda }_{ z}/{{{{{{{\rm{ln}}}}}}{\lambda }_{r}\ ), for equibiaxial compression of agarose (green line) uye fibrin (red line) gels.Iyo inset inoratidza biaxial deformation yegel.e Translocation pressure shanduko ΔPtr, yakajairwa kuita gel kuoma S, inorongerwa sebasa rekumanikidza reshiyo yeagarose uye fibrin microgels.Mavara echiratidzo anoenderana nemavara ari mu (a).Mitsetse yakasvibirira uye yakatsvuka inoratidza hukama hwedzidziso pakati peΔPtr/S uye 1/λr yeagarose uye fibrin gels, zvichiteerana.Chikamu chakasvibiswa chemutsara mutsvuku chinoratidza kuwedzera kweΔPtr pasi pekumanikidzwa kwakasimba nekuda kwekubatana kwe interfiber.
Uyu mutsauko unobatanidzwa neakasiyana maitiro e deformation ye fibrin uye agarose microgel network, iyo inosanganisira inoshanduka24 uye rigid25 tambo, zvichiteerana.Biaxial compression yeanochinjika gels inotungamira mukudzikira kwevhoriyamu yavo uye kuwedzera kwakabatana kwekutarisa uye osmotic kumanikidza, izvo zvinotungamira kune elongation yegel munzira isina muganho.Kurebesa kwekupedzisira kwejeli kunoenderana nechiyero chekuwedzera kweiyo entropic yemahara simba remaketani akatambanudzwa uye kuderera kwesimba remahara reosmosis nekuda kwekudzika kwepolymer kusungwa mune yakatambanudzwa gel.Pasi pekumanikidzwa kwakasimba kwebiaxial, kurebesa kwegel kunowedzera ne λz ≈ 0.6 \({{\lambda}_{{{\rm{r}}}}^{-2/3}}\) (ona mufananidzo 2a mu. hurukuro chikamu 5.3.3).Iko kuchinjika kwekuchinja mumaketani anochinjika uye chimiro cheanoenderana network pamberi uye mushure mekuchengetedza biaxial inoratidzwa muFigs.2b.
Kusiyana neizvi, ma gels ane fibrous senge fibrin anopindura zvakasiyana kune biaxial retention.Iyo filaments yakatarisana zvakanyanya kuenderana negwaro rekumanikidza flex (nekudaro ichidzikisa chinhambwe pakati pe-cross-links), nepo filaments ichinyanya kuenderana negwara rekumanikidza kutwasanuka uye kutambanudza pasi pechiito chesimba re elastic, zvichiita kuti gel rirebe ( Mufananidzo 1).2c) Zvimiro zve SM, MM uye RM zvisina kuchinjwa zvakaratidzwa nekuongorora mifananidzo yavo yeSEM neCFM (Supplementary Discussion Chikamu IV uye Supplementary Figure 9).Nekugadzirisa elastic modulus (E), dhayamita (d), kureba kweprofile (R0), kureba pakati pemagumo (L0 ≈ R0) uye nechepakati angle (ψ0) yetambo muundeformed fibrin microgels (Supplementary Table 2) - 4), tinoona kuti shinda yekupeta modulus \({k}_{{{{{\rm{b)))))))))}=\frac{9\pi E{d}^{4} } {4 {\psi } _{0}^{2}{L}_{0}}\) ishoma pane yayo tensile modulus\({k}_{{{{{{\rm{s}}}}} }} }}=E\frac{\pi {d}^{2}{R}_{0}}{4}\), saka kb/ks ≈ 0.1 (Supplementary Table 4).Nekudaro, pasi pemamiriro ekuchengetedza biaxial gel, tambo dzefibrin dzinokotama zviri nyore, asi ramba kutambanudza.Kurebesa kwefilamentous network pasi pe biaxial compression inoratidzwa muSupplementary Fig. 17.
Isu tinogadzira theoretical affine modhi (Supplementary Hurukuro Chikamu V uye Supplementary Figures 10-16) umo kureba kweiyo fibrous gel inotarwa kubva kunharaunda yakaenzana yemasimba elastic anoshanda mugel uye anofanotaura kuti mune yakasimba biaxial strain λz - 1 pasi pekumanikidzwa
Equation (1) inoratidza kuti kunyangwe pasi pekudzvanyirira kwakasimba (\({\lambda }_{{{\mbox{r))))\,\kusvika\,0\)) pane kuwedzeredzwa kwegel uye kunotevera deformation saturation λz–1 = 0.15 ± 0.05.Maitiro aya anechekuita ne(i) \({\left({k}_{{{({({\rm{b}}}}}}}}}}}/{k}_{{{{{\rm} {s }}}}}}}\kurudyi)}^{1/2}\) ≈ 0.15−0.4 uye (ii) izwi riri mumabhuraketi akaenzana asymptotically akaenzana \(1{{\mbox{/}}} \sqrt { 3 }\) yemabhondi akasimba ebiaxial. Zvakakosha kuziva kuti prefactor \({\left({k}_{({\mbox{b)))))/{k}_{({\mbox{ s))))\kurudyi)}^{1/ 2 }\) haina chekuita nekuoma kweshinda E, asi inotariswa chete nechikamu chechikamu cheshinda d/L0 nepakati pekona yearc. ψ0, iyo yakafanana neSM, MM uye RM (Supplementary Table 4).
Kuti tiwedzere kuratidza mutsauko wekusununguka-kukonzeresa kushushikana pakati peanochinjika uye filamentous gels, isu tinosuma iyo biaxial Poisson's ratio \({\nu }_{{{({\rm{b)))))))} {{\ mbox { =}}}\,\mathop{{\lim}}\limits_{{\lambda}_{{{({({\rm{r}}}}}}}}\kusvika 1}\ frac{{\ lambda } _{{{{\rm{z}}}}}}-1}{1-{\lambda }_{{({\rm{r}}}}}}}}}}, \) inotsanangura isina muganhu kutenderedzwa kwegeri strain mukupindura kuenzana kuenzana mumativi maviri eradial, uye inotambanudza izvi kune mahombe mayunifomu strains \ rm{b}}}}}}}}}^{{{{\rm{eff}}}}}}}} }}=-{{{{{\rm{ln}}}}}}} { \lambda } _{z} /{{({({\rm{ln))))))))} {\lambda }_{{{({\rm{r))))))))}\) .Pamusoro pemuonde.2d inoratidza \({{{{\rm{\nu }}}}}}}}_{{{({\rm{b}}}}}}}}}^{{{{\rm {eff }}}}}}}}\) yeuniform biaxial compression ye flexible (senge agarose) uye rigid (senge fibrin) gels (Supplementary discussion, Chikamu 5.3.4), uye inosimbisa hukama pakati pemisiyano yakasimba mukupindura kuvharirwa. Kune agarose gels pasi pezvirambidzo zvakasimba {\rm{eff}}}}}}}}\) inowedzera kune asymptotic kukosha 2/3, uye yefibrin gels inoderera kusvika zero, kubvira lnλz/lnλr → 0, sezvo λz ichiwedzera ne saturation sezvo λr inowedzera.Ziva kuti mukuyedza, yakavharwa spherical microgels deform inhomogeneously, uye chikamu chavo chepakati chinosangana nekutsikirira kwakasimba;zvisinei, kuwedzera kune kukosha kukuru kwe1 / λr kunoita kuti zvikwanise kuenzanisa kuedza nedzidziso yemajiro akafanana akaremara.
Imwe misiyano muhunhu hwema flexible chain gels uye filamentous gels yakawanikwa nekuda kwekufamba kwavo pachibvumirano.The translocation pressure ΔPtr, normalized to gel stiffness S, yakawedzera nekuwedzera compression (Fig. 2e), asi pa 2.0 ≤ 1 / λr ≤ 3.5, fibrin microgels yakaratidza zvakanyanya kuderera kukosha kweΔPtr / S pasi panguva yekuderera.Kuchengetwa kweagarose microgel kunotungamirira kukuwedzera kweosmotic pressure, iyo inotungamirira kutambanudza gel mukufamba kwenguva yakareba sezvo mapolymer molecules akatambanudzwa (Fig. 2b, kuruboshwe) uye kuwedzera kwekumanikidzwa kwekufambisa ne ΔPtr / S ~( 1/λr)14/317.Pane zvinopesana, chimiro chekuvhara fibrin microgels inotarirwa nechiyero chesimba chetambo dze radial compression uye longitudinal tension, iyo inotungamirira kuhupamhi hwehurefu hwehurefu λz ~\(\sqrt{{k}_{{{{{{{{ \rm{ b))))))))} /{k}_{{{{{{\rm{s}}}}}}}}}}\).Kune 1/λr ≫ 1, shanduko mukumanikidzwa kwekufambisa inoyerwa se 1}{{({\rm{ln))))))\left({{\lambda }}_{{{{{\rm} {r} }}}}}}}^{{-} 1} \kurudyi)\) (Supplementary Hurukuro, Chikamu 5.4), sezvinoratidzwa nemutsara mutsvuku wakasimba mumufananidzo 2e.Nokudaro, ΔPtr haina kumanikidzika kudarika mumajeri agarose.Pakumanikidzana ne 1/λr> 3.5, kuwedzera kukuru kwechikamu chevhoriyamu yefilaments uye kupindirana kwemafilaments evavakidzani kunogumira deformation yejeli uye kunotungamirira kukutsauka kwemigumisiro yekuedza kubva kune zvakafanotaurwa (mutsara wakatsvuka mumufananidzo 2e).Tinogumisa kuti zvakafanana 1/λr uye Δ\({P}_{{{{{{{\rm{tr}}}}}}}}}}_{{{\rm{fibrin}}})) } }}}\) < ΔP < Δ\({P}_{{{{{{{\rm{tr))))))))}}_{{{{\rm{agarose}}}}}} } } }}\) iyo agarose gel ichabatwa ne microchannel, uye gel ye fibrin ine kuoma kwakafanana ichapfuura nayo.ZveΔP <Δ\({P}_{{{{{{\rm{tr))))))))))_{{{{\rm{fibrin))))))))))}\ ), Maviri Maviri gels anovhara chiteshi, asi iyo fibrin gel ichasundira zvakadzika uye kudzvanya zvakanyanya, ichivharira kuyerera kwemvura zvakanyanya.Mhedzisiro inoratidzwa muMufananidzo 2 inoratidza kuti iyo fibrous gel inogona kushanda seplug inoshanda kuderedza kubuda ropa kana kumisa kubuda kweropa kumamota.
Kune rumwe rutivi, fibrin inoumba chivharo chechivharo chinotungamirira ku thromboembolism, chirwere chechirwere umo thrombus inovhara mudziyo pa ΔP < ΔPtr, zvakadai mune mamwe marudzi e-ischemic stroke (Fig. 3a).Iyo isina kusimba kurambidzwa-induced elongation yefibrin microgels yakakonzera kuwedzera kwakasimba kwefibrin concentration yeC / C fibrinogen kana ichienzaniswa neinochinjika cheni gels, uko C uye C fibrinogen inorambidzwa uye isina kuchinjika microgels, zvichiteerana.Polymer concentration mune gel.Mufananidzo 3b unoratidza kuti fibrinogen C / C mu SM, MM, uye RM yakawedzera kudarika kanomwe pa 1 / λr ≈ 4.0, inotungamirirwa nekudziviswa uye kupera simba (Supplementary Fig. 16).
Schematic illustration of occlusion yepakati cerebral artery muuropi.b Restriction-mediated hama kuwedzera mu fibrin concentration mu obstructive SM (solid red circles), MM (solid black squares), uye RM (solid blue triangles).c Kuedza dhizaini yakashandiswa kudzidza kutsemuka kwemafibrin gels anorambidzwa.Mushonga wefluorescently wakanyorwa tPA muTBS wakaiswa jekiseni pachiyero chekuyerera che5.6 × 107 µm3/s uye kuwedzera kudzvinyirira kudonha kwe0.7 Pa kwezvigero zviri perpendicular kune axis refu yeiyo main microchannel.d Yakabatanidzwa multichannel microscopic mufananidzo wezvinodzivisa MM (D0 = 200 µm) pa Xf = 28 µm, ΔP = 700 Pa uye panguva yekupatsanurwa.Mitsara yakatsvuka inoratidza nzvimbo dzekutanga dzemashure uye anterior edges eMM pa tlys = 0. Mavara akasvibira nepinki anoenderana neFITC-dextran (70 kDa) uye tPA yakanyorwa ne AlexaFluor633, maererano.e Nguva-inosiyana-siyana vhoriyamu yeakavharirwa maRM ane D0 ye174 µm (yebhuruu yakavhurika inverted triangle), 199 µm (yebhuruu yakavhurika katatu), uye 218 µm (yebhuruu yakavhurika katatu), zvichiteerana, mune conical microchannel ine Xf = 28 ± 1 µm.zvikamu zvine ΔP 1200, 1800, uye 3000 Pa, zvichiteerana, uye Q = 1860 ± 70 µm3/s.Iyo inset inoratidza RM (D0 = 218 µm) ichivhara iyo microchannel.f Nguva yakasiyana yehuwandu hwehuwandu hweSM, MM kana RM yakaiswa pa Xf = 32 ± 12 µm, pa ΔP 400, 750 uye 1800 Pa uye ΔP 12300 Pa uye Q 12300 munharaunda yeconical ye microchannel, maererano 23600 uye 1m800 µ /s.Xf inomiririra chinzvimbo chepamberi cheiyo microgel uye inosarudza kureba kwayo kubva pakutanga kwe shrinkage.V (tlys) uye V0 ndiyo vhoriyamu yenguva pfupi yeiyo lysed microgel uye vhoriyamu yeiyo isina kukanganiswa microgel, zvichiteerana.Mavara emavara anofambirana nemavara ari muna b.Miseve mitema pa e, f inowirirana nenguva yekupedzisira isati yapfuura mamicrogel kuburikidza neiyo microchannel.Chikero chemu d, e i100 µm.
Kuti tiongorore mhedzisiro yekudzikisira kuyerera kwemvura kuyerera kune inovharira fibrin gels, takadzidza lysis yeSM, MM, uye RM yakapindwa neiyo thrombolytic agent tissue plasminogen activator (tPA).Mufananidzo 3c unoratidza dhizaini yekuyedza yakashandiswa kuongororo yelysis. Pa ΔP = 700 Pa (<ΔPtr) uye chiyero chekuyerera, Q = 2400 μm3 / s, yeTris-buffered saline (TBS) yakasanganiswa ne 0.1 mg/mL ye (fluorescein isothiocyanate) FITC-Dextran, iyo microgel yakavharira microchannel tapered dunhu. Pa ΔP = 700 Pa (<ΔPtr) uye chiyero chekuyerera, Q = 2400 μm3 / s, yeTris-buffered saline (TBS) yakasanganiswa ne 0.1 mg/mL ye (fluorescein isothiocyanate) FITC-Dextran, iyo microgel yakavharira microchannel tapered dunhu. При ΔP = 700 Па (<ΔPtr) uye скорости потока, Q = 2400 мкм3/с, трис-буферного солевого раствора (TBS), смешанного с 0,1 мг/мл (оTCцизренца) микрогель перекрывал сужающийся микроканал. Pa ΔP = 700 Pa (<ΔPtr) uye chiyero chekuyerera, Q = 2400 µm3 / s, yeTris buffered saline (TBS) yakasanganiswa ne 0.1 mg / mL (fluorescein isothiocyanate) FITC-dextran, iyo microgel yakavhara microchannel inoshandura.dunhu.在DS微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 мг/мл (флуоресцеинизотиоцианат) FITC-дек0P Δпанат FITC-декстра сти потока Q = 2400 мкм3/с Конические области микроканалов. Microgels yakavharwa apo Tris buffered saline (TBS) yakasanganiswa ne 0.1mg/mL (fluorescein isothiocyanate) FITC-dextran pa ΔP = 700 Pa (<ΔPtr) uye chiyero chekuyerera Q = 2400 µm3 / s Conical nzvimbo dze microchannels.Iyo yekumberi chinzvimbo Xf yeiyo microgel inotarisa kureba kwayo kubva kune yekutanga shrinkage point X0.Kupinza lysis, mhinduro yefluorescently yakanyorwa tPA muTBS yakabayiwa kubva kuchiteshi chiri orthogonally kusvika kune refu axis yeiyo main microchannel.
Apo tPA mhinduro yakasvika kune occlusal MM, kumucheto kwemashure kwe microgel kwakava kusina kujeka, zvichiratidza kuti fibrin cleavage yakanga yatanga panguva tlys = 0 (Fig. 3d uye Supplementary Fig. 18).Munguva yefibrinolysis, dhayi-yakanyorwa tPA inounganidza mukati meMM uye inosunga kune fibrin strands, izvo zvinotungamirira kukuwedzera zvishoma nezvishoma muhukuru hwepinki ruvara rwe microgels.At tlys = 60 min, iyo MM zvibvumirano nekuda kwekuparara kwechikamu chayo chekumashure, uye chinzvimbo chekutungamira kwayo Xf inochinja zvishoma.Mushure mokunge 160 min, MM yakabvumirana zvakasimba yakaramba ichibvumirana, uye pa tlys = 161 min, yakagadziriswa, nokudaro kudzorera kuyerera kwemvura kuburikidza ne microchannel (Fig. 3d uye Supplementary Fig. 18, kona yekurudyi).
Pamusoro pemuonde.3e inoratidza lysis-mediated nguva-inotsamira kuderera kwevhoriyamu V (tlys) yakajairwa kune yekutanga vhoriyamu V0 yeakasiyana saizi fibrin microgels.CO ine D0 174, 199, kana 218 µm yakaiswa mu microchannel ine ΔP 1200, 1800, kana 3000 Pa, zvakateerana, uye Q = 1860 ± 70 µm3 / s kuvhara microchannel (Fig. 3e, inset).chikafu.Iwo ma microgels anodzikira zvishoma nezvishoma kusvika adiki zvekuti anogona kupfuura nemumigero.Kuderera kwehuwandu hwakakosha hweCO ine yakakura yekutanga dhayamita inoda nguva yakareba yelysis.Nekuda kwekuyerera kwakafanana kuburikidza nehukuru hwakasiyana maRM, cleavage inoitika pamwero wakafanana, zvichikonzera kugaya kwezvikamu zvidiki zvemaRM makuru uye kunonoka kwavo kutamiswa.Pamusoro pemuonde.3f inoratidza kudzikiswa kwehama muV (tlys)/V0 nekuda kwekutsemuka kweSM, MM, uye RM paD0 = 197 ± 3 µm yakarongwa sebasa retlys.Kune SM, MM uye RM, isa imwe neimwe microgel mune microchannel ine ΔP 400, 750 kana 1800 Pa uye Q 12300, 2400 kana 1860 µm3 / s, zvichiteerana.Kunyange zvazvo dzvinyiriro yakashandiswa kune SM yakanga iri 4.5 nguva yakaderera pane iyo yeRM, kuyerera kuburikidza neSM kwaive kwakasimba kudarika katanhatu nekuda kwekukwirira kwepamusoro kweSM, uye shrinkage ye microgel yakaderera kubva SM kusvika MM uye RM. .Semuenzaniso, pa tlys = 78 min, SM yainyanya kunyungudika uye kutamiswa, nepo MM nePM vakaramba vachivhara ma microchannels, kunyangwe vachingochengeta 16% uye 20% yevhoriyamu yavo yekutanga, zvichiteerana.Mhedzisiro iyi inoratidza kukosha kwe convection-mediated lysis ye constricted fibrous gels uye inoenderana nemishumo yekukurumidza kugaya kwemagwamba ane yakaderera fibrin content.
Saka, basa redu rinoratidza kuedza uye ne theoretically nzira iyo filamentous gels inopindura kune biaxial confinement.Maitiro emagetsi emagetsi munzvimbo shoma anotarirwa neasymmetry yakasimba yesimba rekutambudzika kwefilaments (yakapfava mukutsikirira uye yakaoma mukushushikana) uye chete nechiyero chechikamu uye kupetwa kwemafilaments.Kuita uku kunoguma nekurebesa kushoma kwemafibrous gels ari mumacapillaries akamanikana, yavo biaxial Poisson's ratio ichidzikira nekuwedzera kudzvanyirirwa uye kushomeka kwechiedza chidiki.
Sezvo biaxial iine zvinyoro zvinyoro zvinogomara zvimedu zvichishandiswa mumhando dzakasiyana dzetekinoroji, mhedzisiro yedu inosimudzira kuvandudzwa kwezvinhu zvitsva zvefibrous.Kunyanya, iyo biaxial kuchengetwa kweiyo filamentous gels mune yakamanikana capillaries kana machubhu inotungamira kune yavo yakasimba compaction uye kuderera kwakanyanya kwepermeability.Iyo yakasimba inhibition yemvura inoyerera kuburikidza neocclusive fibrous gels ine zvakanakira kana yakashandiswa semapulagi ekudzivirira kubuda ropa kana kuderedza kubuda kweropa kune malignancies33,34,35.Kune rumwe rutivi, kuderera kwemvura inoyerera kuburikidza neocclusal fibrin gel, nokudaro inhibiting convective-mediated thrombus lysis, inopa chiratidzo chekunonoka lysis ye occlusal clots [27, 36, 37].Yedu yekuenzanisira sisitimu inhanho yekutanga yekunzwisisa zvinorehwa nemuchina mhinduro yefibrous biopolymer hydrogels kune biaxial kuchengetedza.Kubatanidza masero eropa kana maplatelet muzvinovhiringidza fibrin gels zvinokanganisa maitiro avo ekurambidza 38 uye richava danho rinotevera mukufumura maitiro ezvakanyanya kuoma biologically akakosha masisitimu.
Mareagents anoshandiswa kugadzira fibrin microgels uye kugadzira MF zvishandiso zvinotsanangurwa muSupplementary Information (Supplementary Methods Chikamu 2 ne4).Fibrin microgels akagadzirwa ne emulsifying yakasanganiswa mhinduro ye fibrinogen, Tris buffer uye thrombin mukuyerera inotarisa MF mudziyo, ichiteverwa nedonhwe gelation.Bovine fibrinogen solution (60 mg/ml muTBS), Tris buffer uye bovine thrombin solution (5 U/ml mu 10 mM CaCl2 solution) yaishandiswa pachishandiswa pombi dzesirinji dzakazvimiririra (PhD 200 Harvard Apparatus PHD 2000 Syring Pump).kuvhara MF, USA).F-oiri inoenderera mberi chikamu ine 1 wt.% block copolymer PFPE-P(EO-PO)-PFPE, yakaunzwa muchikamu cheMF pachishandiswa chetatu sirinji pombi.Madonhwe akaumbwa mumudziyo weMF anounganidzwa mu 15 ml centrifuge chubhu ine F-mafuta.Isa machubhu mubhavhu remvura pa37 °C kwe1 h kuti fibrin gelation ipedze.FITC yakanyorwa kuti fibrin microgels yakagadzirwa nekusanganisa bovine fibrinogen neFITC yakanyorwa kuti human fibrinogen muchiyero che33:1, zvichiteerana.Nzira yacho yakafanana neyekugadzirira fibrin microgels.
Shandura ma microgels kubva kumafuta F kuenda kuTBS nekuisa centrifuging kupararira pa185 g kwema 2 min.Iwo ma microgel akadhindwa akaparadzirwa mumafuta F akasanganiswa ne 20 wt.% perfluorooctyl doro, ndokuzoparadzirwa muhexane ine 0.5 wt.% Span 80, hexane, 0.1 wt.% Triton X mumvura uye TBS.Pakupedzisira, ma microgels akaparadzirwa muTBS ine 0.01 wt% Pakati pe20 uye akachengetwa pa 4 ° C kweanenge mavhiki 1-2 asati aedzwa.
Kugadzirwa kwechigadzirwa cheMF kunotsanangurwa muSupplementary Information (Supplementary Methods Chikamu 5).Muchiitiko chekuedza, kukosha kwakanaka kwe ΔP kunotarirwa nehupamhi hwehurefu hwemadziva akabatanidzwa mberi uye shure kweMF device yekuunza microgels nehupamhi hwe150
Data inotsigira zvakabuda muchidzidzo ichi inowanika kubva kuvanyori vakasiyana kana yakumbirwa.Raw SEM mifananidzo yefibrin gels, mbishi TEM mifananidzo yefibrin gels isati yasvika uye mushure meinoculation, uye iyo huru yekuisa data yeFigure 1 uye 2. 2 uye 3 inopiwa mufivha data data.Ichi chinyorwa chinopa data rekutanga.
Litvinov RI, Peters M., de Lange-Loots Z. uye Weisel JV fibrinogen uye fibrin.MuMacromolecular Protein Complex III: Chimiro uye Basa (ed. Harris, JR naMarles-Wright, J.) 471-501 https://doi.org/10.1007/978-3-030-58971-4_15 ( Springer naCham, 2021).
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