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Moeli oa li-fibrous hydrogels ho li-capillaries tse tšesaane ke tsa bohlokoa haholo lits'ebetsong tsa bioloji le tsa biomedical.Khatello le khatello ea uniaxial ea li-fibrous hydrogel li 'nile tsa ithutoa ka mokhoa o pharaletseng, empa karabelo ea bona ea ho boloka biaxial ka li-capillaries e ntse e sa hlahlojoe.Mona, re bontša ka liteko le ka khopolo hore li-gels tsa filamentous li arabela ka mokhoa o fapaneng ka mokhoa o fapaneng ho thibela ho feta li-gels tsa ketane tse tenyetsehang ka lebaka la asymmetry ka thepa ea mechine ea li-filaments tsa constituent, tse bonolo ha li hatelloa le tse thata ka har'a tsitsipano.Tlas'a ho bolokoa ka matla, gel e nang le fibrous e bonts'a bolelele bo fokolang le ho fokotseha ho hoholo hoa karo-karolelano ea biaxial Poisson ho ea ho zero, e leng se bakang ho kopana ho matla ha gel le ho kenella ha metsi ho fosahetseng ka gel.Liphetho tsena li bonts'a khanyetso ea occlusive thrombi e otlolohileng ho lysis ke mahlahana a kalafo le ho susumetsa nts'etsopele ea endovascular embolization e sebetsang ho tloha ho li-gel tsa fibrous ho emisa ho tsoa mali ho vascular kapa ho thibela phepelo ea mali ea lihlahala.
Marang-rang a li-fibrous ke li-block tsa motheo tsa meralo le tse sebetsang tsa lisele le lisele tse phelang.Actin ke karolo e kholo ea cytoskeleton1;fibrin ke ntho ea bohlokoa ho folisa maqeba le thrombus formation2, 'me collagen, elastin le fibronectin ke likarolo tsa matrix a extracellular a liphoofolo3.Marang-rang a hlaphollotsoeng a li-biopolymer tsa fibrous e se e le lisebelisoa tse nang le ts'ebeliso e pharalletseng ho boenjiniere ba lisele4.
Marang-rang a filamentous a emela sehlopha se arohaneng sa lintho tse bonolo tsa baeloji tse nang le thepa ea mochini e fapaneng le marang-rang a feto-fetohang a limolek'hule5.Tse ling tsa thepa ena li bile teng nakong ea ho iphetola ha lintho ho laola karabelo ea lintho tsa tlhaho ho deformation6.Mohlala, marang-rang a likhoele a bonts'a elasticity ea mela ho mefuta e menyane7,8 ha ka mefuta e meholo e bonts'a ho satalla ho eketsehileng9,10, ka hona ho boloka botšepehi ba lisele.Litlamorao bakeng sa lisebelisoa tse ling tsa mochini oa li-gel tsa fibrous, joalo ka khatello ea maikutlo e mpe e tloaelehileng karabelong ea "shear strain11,12", ha li e-so fumanehe.
Thepa ea mechine ea li-semi-flexible fibrous hydrogels e 'nile ea ithutoa tlas'a tsitsipano ea uniaxial13,14 le compression8,15, empa khatello ea bona ea bolokolohi e bakoang ke tokoloho ka li-capillaries tse moqotetsane kapa li-tubes ha e e-s'o ithutoe.Mona re tlaleha liphetho tsa liteko mme re fana ka maikutlo a mokhoa oa boits'oaro ba li-fibrous hydrogels tlas'a biaxial retention liteisheneng tsa microfluidic.
Li-microgels tsa Fibrin tse nang le litekanyo tse sa tšoaneng tsa fibrinogen le li-thrombin le bophara ba D0 ho tloha ho 150 ho ea ho 220 µm li ile tsa hlahisoa ka mokhoa oa microfluidic (Figure ea Tlatsetso 1).Ka feiga.1a e bonts'a litšoantšo tsa li-microgels tse ngotsoeng ka fluorochrome tse fumanoeng ho sebelisoa confocal fluorescence microscopy (CFM).Li-microgels li chitja, li na le polydispersity e ka tlase ho 5%, 'me li tšoana ka sebopeho ho pholletsa le sekala se hlahlobiloeng ke CFM (Tlhahlobo ea Tlatsetso le Lifilimi S1 le S2).Karolelano ea boholo ba pore ea microgels (e khethiloeng ka ho lekanya Darcy permeability16) e fokotsehile ho tloha 2280 ho ea ho 60 nm, litaba tsa fibrin li eketsehile ho tloha 5.25 ho ea 37.9 mg / mL, 'me mahloriso a thrombin a fokotsehile ho tloha 2.56 ho ea ho 0.27 units / mL, ka ho latellana.(Tlhahisoleseling e 'Ngoe).Raese.2), 3 le tafole ea tlatsetso 1).Boima bo lumellanang ba microgel bo eketseha ho tloha ho 0,85 ho ea ho 3.6 kPa (Supplementary Fig. 4).E le mehlala ea li-gel tse entsoeng ka liketane tse tenyetsehang, li-microgels tsa agarose tsa mefuta e sa tšoaneng li sebelisoa.
Setšoantšo sa fluorescence microscopy sa fluorescein isothiocyanate (FITC) se ngotsoeng PM se emisitsoe ho TBS.Sekhahla sa bar ke 500 µm.b SEM litšoantšo tsa SM (holimo) le RM (ka tlaase).Scale bar 500 nm.c Sets'oants'o sa sets'oants'o sa kanale ea microfluidic e nang le kanale e kholo (diameter dl) le sebaka se moqotetsane sa sebopeho sa khoune se nang le angle ea ho kena α ea 15 ° le bophara ba dc = 65 µm.d Ho tloha ho le letšehali ho ea ka ho le letona: Litšoantšo tsa microscope tsa RM (diameter D0) likanaleng tse kholo, libaka tsa conical le constriction (e fokotsa bolelele ba gel Dz).Sekhahla sa bar ke 100 µm.e, f litšoantšo tsa TEM tsa RM e sa fetoheng (e) le RM e koetsoeng (f), e tsitsitseng hora e le 'ngoe ka constriction 1/λr = 2.7, e lateloa ke ho lokolloa le ho lokisa 5% ea boima.glutaraldehyde ho TBS.Bophara ba CO e sa fetoheng ke 176 μm.Sekhahla se seholo ke 100 nm.
Re tsepamisitse maikutlo ho li-microgels tsa fibrin tse nang le boima ba 0.85, 1.87 le 3.6 kPa (eo ka mor'a moo e bitsoang li-microgels tse bonolo (SM), li-microgels tse thata tse mahareng (MM) le li-microgel tse thata (RM), ka ho latellana).Letoto lena la ho satalla ha gel ea fibrin ke la tatellano ea boholo bo lekanang le ea ho koala mali18,19 'me kahoo li-gel tsa fibrin tse ithutoang mosebetsing oa rona li amana ka ho toba le mekhoa ea sebele ea likokoana-hloko.Ka feiga.1b e bonts'a litšoantšo tse holimo le tse ka tlase tsa meaho ea SM le RM e fumanoeng ho sebelisoa microscope ea elektronike (SEM), ka ho latellana.Ha ho bapisoa le mehaho ea RM, marang-rang a SM a thehoa ka likhoele tse teteaneng le lintlha tse fokolang tsa makala, tse lumellanang le litlaleho tsa pejana 20, 21 (Supplementary Fig. 5).Phapang ea sebopeho sa hydrogel e tsamaisana le mokhoa oa thepa ea eona: ho kenella ha gel ho fokotseha ka ho fokotseha ha boholo ba pore ho tloha ho SM ho ea ho MM le RM (Letlapa la 1 la Tlatsetso), 'me ho satalla ha gel ho khutlela morao.Ha ho liphetoho tsa sebopeho sa microgel tse ileng tsa hlokomeloa ka mor'a ho boloka ho 4 ° C bakeng sa matsatsi a 30 (Fig. 6 ea Tlatsetso).
Ka feiga.1c e bonts'a setšoantšo sa mocha oa microfluidic o nang le karolo e chitja e nang le sefapano (ho tloha ka letsohong le letšehali ho ea ho le letona): mocha o moholo o nang le bophara ba dl moo microgel e lulang e sa fetohe, karolo e bōpehileng joaloka khoune e nang le bophara ba dc
Ka feiga.1e, 1f e bonts'a litšoantšo tsa transmission electron microscopy (TEM) tsa mekhoa ea RM e sa fetoheng le e fokolang ea biaxially.Ka mor'a khatello ea RM, boholo ba pore ea microgel bo fokotsehile haholo 'me sebōpeho sa bona sa fetoha anisotropic ka boholo bo fokolang ka tataiso ea khatello, e lumellanang le tlaleho ea pejana ea 23.
Khatello ea Biaxial nakong ea ho honyela e etsa hore microgel e hole ka lehlakoreng le se nang moeli ka coefficient λz = \({D}_{{{{{{\rm{z}}}}}}}/\({D }_ { 0}\) , moo \({D}_{{{{({({\rm{z}}}}}}}}\) e leng bolelele ba microgel e koetsoeng Setšoantšo sa 2a se bontša phetoho ho λzvs .1/ λr Hoa makatsa hore, tlas'a khatello e matla ea 2.4 ≤ 1/λr ≤ 4.2, fibrin microgels e bonts'a bolelele bo sa tsotelleng ba 1.12 +/- 0.03 λz, e amehang hanyane feela ke boleng ba 1/λr. li-microgels tse fokolang tsa agarose, tse bonoang le ha ho hatelloa ho fokolang 1/λr = 2.6 ho elong e kholoanyane λz = 1.3.
liteko tsa Agarose microgel tse nang le moduli e fapaneng ea elastic (2.6 kPa, daemane e tala e bulehileng; 8.3 kPa, selikalikoe se sootho se bulehileng; 12.5 kPa, lisekoere tse bulehileng tsa lamunu; 20.2 kPa, kgutlotharo e bulehileng ea magenta e butsoitseng) le SM (e khubelu e tiileng) Fetola ka bolelele bo lekantsoeng λz ( lisekoere), MM (masekoere a matšo a tiileng) le RM (likhutlo-tharo tse putsoa tse tiileng).Mela e tiileng e bontša λz e boletsoeng esale pele ka theory bakeng sa agarose (mola o motala) le fibrin microgels (mela le matšoao a mebala e tšoanang).b, c Phanele e ka holimo: setšoantšo sa schematic sa liketane tsa marang-rang tsa agarose (b) le fibrin (c) pele (ka ho le letšehali) le ka morao (ka ho le letona) khatello ea biaxial.Ka tlase: Sebopeho sa marang-rang a tsamaisanang pele le ka mor'a deformation.Litaelo tsa khatello ea x le y li bonts'oa ka metsu ea magenta le e sootho, ka ho latellana.Setšoantšong se ka holimo, liketane tsa marang-rang tse shebaneng le litsela tsena tsa x le y li bontšoa ka mela e tšoanang ea magenta le e sootho, 'me liketane tse lebisitsoeng ho tataiso ea z li emeloa ke mela e tala.Ka gel ea fibrin (c), mela e pherese le e sootho ka mahlakoreng a x le y e kobeha ho feta boemong bo sa fetoheng, 'me mela e tala e ka lehlakoreng la z e kobeha le ho otlolla.Khohlano pakeng tsa litsela tsa khatello le tsitsipano e fetisoa ka likhoele tse nang le litsela tse bohareng.Ka li-gels tsa agarose, liketane ka mahlakoreng 'ohle li khetholla khatello ea osmotic, e fanang ka tlatsetso e kholo ho deformation ea gel.d Phetoho e lekanyelitsoeng ho biaxial Poisson's ratio, } }^{{{{{\rm{eff}}}}}}}} =-{{{{\rm{ln}}}}}}}{\lambda }_{ z}/{{{{{{{ \rm{ln}}}}}}{\lambda }_{r}\ ), bakeng sa compression ea equibiaxial ea li-gel tsa agarose (mola o motala) le fibrin (mola o mofubelu).Inset e bonts'a deformation ea biaxial ea gel.Phetoho ea khatello ea Translocation ΔPtr, e tloaelehileng ho gel stiffness S, e reriloe e le mosebetsi oa compression ratio bakeng sa agarose le fibrin microgels.Mebala ea matšoao e lumellana le mebala e ho (a).Mela e tala le e khubelu e bontša kamano ea khopolo-taba lipakeng tsa ΔPtr/S le 1/λr bakeng sa li-gel tsa agarose le fibrin, ka ho latellana.Karolo e senyehileng ea mola o mofubelu e bontša keketseho ea ΔPtr tlas'a khatello e matla ka lebaka la litšebelisano tsa interfiber.
Phapang ena e amahanngoa le mekhoa e fapaneng ea deformation ea marang-rang a fibrin le agarose microgel, a nang le likhoele tsa flexible24 le rigid25, ka ho latellana.Khatello ea Biaxial ea li-gel tse feto-fetohang e lebisa ho fokotseha ha molumo oa tsona le keketseho e amanang le khatello ea maikutlo le khatello ea osmotic, e lebisang ho phahamisoeng ha gel ka tsela e sa lekanyetsoang.Katoloso ea ho qetela ea gel e ipapisitse le ho leka-lekana ha keketseho ea matla a mahala a entropic a liketane tse otlolohileng le ho fokotseha ha matla a mahala a osmosis ka lebaka la khatello e tlase ea polima ka gel e otlolohileng.Tlas'a khatello e matla ea biaxial, bolelele ba gel bo eketseha ka λz ≈ 0.6 \ ({{\ lambda}_{{{\rm{r}}}}^{-2/3}}\) (sheba Setšoantšo sa 2a ho karolo ea lipuisano 5.3.3).Liphetoho tse lumellanang le liketane tse feto-fetohang le sebopeho sa marang-rang a tsamaisanang pele le ka mor'a ho boloka biaxial ho bontšoa ho Figs.2b.
Ka lehlakoreng le leng, li-gel tsa fibrous tse kang fibrin ka tlhaho li arabela ka tsela e fapaneng ho boloka biaxial.Li-filaments tse shebaneng haholo le tataiso ea compression flex (ka tsela eo li fokotsa sebaka se pakeng tsa li-cross-link), ha likhoele li lebile ka lehlakoreng la khatello li otloloha 'me li otlolla tlas'a ketso ea matla a elastic, e leng se etsang hore gel e lelefale. Setšoantšo sa 1).2c) Mehaho ea SM, MM le RM e sa fetoheng li ne li khetholloa ka ho hlahloba litšoantšo tsa bona tsa SEM le CFM (Karolo ea Puisano ea Tlatsetso ea IV le Setšoantšo sa Tlatsetso 9).Ka ho khetholla modulus elastic (E), bophara (d), bolelele ba profil (R0), sebaka se pakeng tsa lipheletsong (L0 ≈ R0) le angle e bohareng (ψ0) ea likhoele tse nang le li-microgel tse sa fetoheng tsa fibrin (Letlapa la Tlatsetso 2) - 4), re fumana hore khoele e kobang modulus \({k}_{{{{{{\rm{b))))))))))}=\frac{9\pi E{d}^{4} } {4 {\psi } _{0}^{2}{L}_{0}}\) e tlase haholo ho feta modulus ea eona ea ho tiea\({k}_{{{{{{\rm{s}}}}}} }} }}=E\frac{\pi {d}^{2}{R}_{0}}{4}\), kahoo kb/ks ≈ 0.1 (Letlapa la Tlatsetso 4).Kahoo, tlas'a maemo a ho boloka li-gel tsa biaxial, likhoele tsa fibrin li kobeha habonolo, empa li hana ho otlolla.Ho atolosoa ha marang-rang a filamentous tlas'a khatello ea biaxial ho bontšoa ho Supplementary Fig. 17.
Re etsa mohlala oa theoretical affine (Karolo ea Phatlalatso ea V le Lipalo tsa Tlatsetso 10-16) moo ho lelefala ha gel ea fibrous ho khethoang ho tsoa tekano ea sebaka sa matla a elastic a sebetsang ka har'a gel le ho bolela esale pele hore ka mokhoa o matla oa biaxial λz - 1 tlas'a thibelo
Equation (1) e bontša hore le tlas'a khatello e matla (\({\ lambda }_{{{\mbox{r))))\,\ho \,0\)) ho na le katoloso e nyane ea gel le deformation e latelang ea elongation holim'a. saturation λz–1 = 0.15 ± 0.05.Boitšoaro bona bo amana le (i) \({\ left({k}_{{{{({\rm{b}}}}}}}}}}/{k}_{{{{{\rm {s }}}}}}}\ ka ho le letona)}^{1/2}\) ≈ 0.15−0.4 le (ii) lentsoe ka masakaneng a lisekoere ha le lekane \(1{{\mbox{/}}} \sqrt {3}\) bakeng sa libonto tse matla tsa biaxial. Ho bohlokoa ho hlokomela hore selelekela \({\left({k}_{({\mbox{b)))))/{k}_{({\mbox{ s))))\right)}^{1/ 2 }\) ha e amane letho le ho satalla ha khoele E, empa e khethoa feela ke karolo ea karolo ea khoele d/L0 le ntlha e bohareng ea arc. ψ0, e tšoanang le SM, MM le RM (Supplementary Table 4).
Ho tsoela pele ho totobatsa phapang pakeng tsa khatello e bakoang ke tokoloho pakeng tsa li-flexible le li-gel filamentous, re hlahisa karolelano ea biaxial Poisson \({\nu }_{{{({\rm{b)))))))} {{\ mbox { =}}\,\mathop{{\lim}}\meedi_{{\lambda}_{{{({({\rm{r}}}}}}}}\ho fihla 1}\ frac{{\ lambda } _{{{{\rm{z}}}}}-1}{1-{\lambda }_{{({\rm{r}}}}}}}}}, \) e hlalosa se se nang moeli tlhophiso ea khatello ea gel ho latela khatello e lekanang ka mahlakoreng a mabeli a radial, 'me e fetisetsa sena ho mefuta e meholo e ts'oanang \ rm{b}}}}}}}}}} ^{{{{\rm{eff}}}}}}} }}=-{{{{{\rm{ln}}}}}}}} { \lambda } _{z} /{{({({\rm{ln))))))))} {\lambda }_{{{({\rm{r))))))))}\) .Ka feiga.Lipontšo tsa 2d \({{{{{\rm{\nu }}}}}}}}_{{{({\rm{b}}}}}}}}^{{{{{\rm {eff }}}}}}}}}\) bakeng sa compression e tšoanang ea biaxial ea flexible (e kang agarose) le rigid (joaloka fibrin) li-gel (Moqoqo oa tlatsetso, Karolo ea 5.3.4), 'me e totobatsa kamano pakeng tsa liphapang tse matla tsa likarabo tsa ho koalloa. Bakeng sa li-gel tsa agarose tlas'a lithibelo tse matla {\rm{eff}}}}}}}}}\) e eketseha ho boleng ba asymptotic 2/3, 'me bakeng sa li-gel tsa fibrin e fokotseha ho ea ho zero, kaha lnλz/lnλr → 0, kaha λz e eketseha ka saturation ha λr e ntse e eketseha.Hlokomela hore litekong, li-microgel tse koetsoeng tse chitja li deform inhomogeneously, 'me karolo ea bona e bohareng e ba le khatello e matla;leha ho le joalo, extrapolation ho boleng bo boholo ba 1/λr e etsa hore ho khonehe ho bapisa teko le khopolo ea li-gel tse holofetseng ka mokhoa o tšoanang.
Phapang e 'ngoe ea boitšoaro ba li-gels tsa ketane tse feto-fetohang le li-gel filamentous li ile tsa fumanoa ka lebaka la ho tsamaea ha tsona ha li kopana.Khatello ea translocation ΔPtr, e tloaelehileng ho boima ba gel S, e eketsehile ka khatello e ntseng e eketseha (setšoan.Ho bolokoa ha agarose microgel ho lebisa ho eketseha ha khatello ea osmotic, e lebisang ho otlolloa ha gel ka tsela ea longitudinal ha limolek'hule tsa polymer li otlolloa (setšoantšo sa 2b, ka ho le letšehali) le ho eketseha ha khatello ea translocation ka ΔPtr / S ~( 1/λr)14/317.Ho fapana le hoo, sebopeho sa li-microgel tsa fibrin tse koetsoeng li khethoa ke matla a matla a likhoele tsa khatello ea radial le tsitsipano ea longitudinal, e lebisang ho deformation e phahameng ea longitudinal λz ~\(\sqrt{{k}_{{{{{{{{ \rm{ b))))))))} /{k}_{{{{{{{\rm{s}}}}}}}}}}\).Bakeng sa 1/λr ≫ 1, phetoho ea khatello ea phalliso e lekantsoe joalo ka 1}{{({\rm{ln)))))))\left({{\lambda }}_{{{{{{\rm} {r} }}}}}}}^{{-} 1} \ ka ho le letona)\) (Puisano ea Tlatsetso, Karolo ea 5.4), joalo ka ha ho bontšoa ke mola o mofubelu o tiileng setšoantšong sa 2e.Kahoo, ΔPtr ha e na khatello e tlase ho feta ka li-gels tsa agarose.Bakeng sa compressions le 1 / λr> 3.5, keketseho e khōlō ea karolo ea molumo oa likhoele le ho sebelisana ha likhoele tsa boahelani li fokotsa deformation e eketsehileng ea gel 'me e lebisa ho kheloha liphello tsa liteko ho tloha ho bolela esale pele (mola o matheba o mofubelu setšoantšong sa 2e).Re etsa qeto ea hore bakeng sa eona 1/λr le Δ\({P}_{{{{{{{\rm{tr}}}}}}}}}_{{{\rm{fibrin}}} )) } }}}\) < ΔP < Δ\({P}_{{{{{{{\rm{tr))))))))}}_{{{\rm{agarose}}}}} } } }}\) gel ea agarose e tla nkoa ke microchannel, 'me gel ea fibrin e nang le boima bo tšoanang e tla feta ho eona.Bakeng sa ΔP < Δ\({P}_{{{{{{\rm{tr))))))))))_{{{{{\rm{fibrin))))))))))}\ ), Li-gel tse peli ka bobeli li tla thibela mocha, empa gel ea fibrin e tla phunyeletsa ka ho teba le ho hatella ka katleho, e thibela ho phalla ha metsi ka katleho.Liphetho tse bontšitsoeng ho Setšoantšo sa 2 li bonts'a hore gel e nang le fibrous e ka sebetsa e le plug e sebetsang ho fokotsa ho tsoa mali kapa ho thibela phepelo ea mali ho lihlahala.
Ka lehlakoreng le leng, fibrin e etsa scaffold ea clot e lebisang ho thromboembolism, boemo ba pathological moo thrombus e koalang sekepe ho ΔP <ΔPtr, joalo ka mefuta e meng ea ischemic stroke (Fig. 3a).Katoloso e fokolang e bakoang ke lithibelo ea li-microgel tsa fibrin e bakile keketseho e matla ea khatello ea fibrin ea C/C fibrinogen ha e bapisoa le li-flexible chain gels, moo C le C fibrinogen li thibetsoeng le li-microgel tse sa fetoheng, ka ho latellana.Polase ea polymer ka gel.Setšoantšo sa 3b se bontša hore fibrinogen C / C ho SM, MM, le RM e eketsehile ho feta makhetlo a supileng ho 1 / λr ≈ 4.0, e tsamaisoang ke thibelo le ho felloa ke metsi (Supplementary Fig. 16).
Sets'oants'o sa moralo oa ho koaloa ha mothapo oa boko bo bohareng bokong.b Keketseho e amanang le lithibelo e amanang le thibelo ea khatello ea fibrin ho SM e thibelang (li-circles tse khubelu tse tiileng), MM (li-square tse tiileng tse ntšo), le RM (li-triangles tse putsoa tse tiileng).c Moralo oa liteko o sebelisetsoang ho ithuta ho petsoha ha li-gel tsa fibrin tse thibetsoeng.Tharollo ea tPA e ngotsoeng ka fluorescently ho TBS e ile ea kenngoa ka tekanyo ea phallo ea 5.6 × 107 µm3 / s le ho theoha ho eketsehileng ha khatello ea 0.7 Pa bakeng sa likanale tse fumanehang ka mokhoa o pota-potileng ho ea ho axis e telele ea microchannel e kholo.d Setšoantšo sa microscopic se kopantsoeng sa mechine e mengata ea MM e thibelang (D0 = 200 µm) ho Xf = 28 µm, ΔP = 700 Pa le nakong ea ho arohana.Mela e matheba e otlolohileng e bonts'a maemo a pele a mahlakoreng a ka morao le a ka pele a MM ho tlys = 0. Mebala e tala le e pinki e lumellana le FITC-dextran (70 kDa) le tPA e ngotsoeng ka AlexaFluor633, ka ho latellana.e Bophahamo bo feto-fetohang ba nako ea li-RM tse koaletsoeng ka D0 ea 174 µm (khutlotharo e putsoa e butsoitseng e putsoa), 199 µm (khutlotharo e putsoa e bulehileng), le 218 µm (khutlotharo e bulehileng e putsoa), ka ho latellana, ka har'a mocha o mosoeu o nang le Xf = 28 ± 1 µm.likarolo li na le ΔP 1200, 1800, le 3000 Pa, ka ho latellana, le Q = 1860 ± 70 µm3/s.Sets'oants'o se bonts'a RM (D0 = 218 µm) e hokela mocha o monyane.f Phapang ea nako ea bophahamo bo lekanang ba SM, MM kapa RM e behiloeng ho Xf = 32 ± 12 µm, ho ΔP 400, 750 le 1800 Pa le ΔP 12300 Pa le Q 12300 sebakeng sa conical sa microchannel, ka ho latellana 23600 µm800 le 1m800 µ /s.Xf e emela boemo bo ka pele ba microgel mme e lekanya sebaka sa eona ho tloha qalong ea shrinkage.V (tlys) le V0 ke molumo oa nakoana oa lysed microgel le molumo oa microgel e sa tsitsang, ka ho latellana.Mebala ea litlhaku e lumellana le mebala e ho b.Metsu e ntšo ho e, f e lumellana le motsotso oa ho qetela oa nako pele li-microgel li feta ka har'a microchannel.Sekala sa d, e ke 100 µm.
Ho etsa lipatlisiso ka phello ea thibelo phokotsong ea phallo ea mokelikeli ho pholletsa le li-gels tsa fibrin tse thibelang, re ithutile lysis ea SM, MM, le RM e kentsoeng ka thrombolytic agent tissue plasminogen activator (tPA).Setšoantšo sa 3c se bontša moralo oa liteko o sebelisetsoang liteko tsa lysis. Ho ΔP = 700 Pa (<ΔPtr) le sekhahla sa phallo, Q = 2400 μm3/s, ea Tris-buffered saline (TBS) e kopantsoeng le 0.1 mg/mL ea (fluorescein isothiocyanate) FITC-Dextran, microgel e ile ea koala mocha o monyane o taped. sebaka. Ho ΔP = 700 Pa (<ΔPtr) le sekhahla sa phallo, Q = 2400 μm3/s, ea Tris-buffered saline (TBS) e kopantsoeng le 0.1 mg/mL ea (fluorescein isothiocyanate) FITC-Dextran, microgel e ile ea koala mocha o monyane o taped. sebaka. При ΔP = 700 Па (<ΔPtr) le скорости потока, Q = 2400 мкм3/с, трис-буферного солевого раствора (TBS), смешанного с 0,1 мг/млл (флицизренценство) микрогель перекрывал сужающийся микроканал. Ho ΔP = 700 Pa (<ΔPtr) le sekhahla sa phallo, Q = 2400 µm3/s, ea Tris buffered saline (TBS) e kopantsoeng le 0.1 mg/mL (fluorescein isothiocyanate) FITC-dextran, microgel e ile ea koala microchannel e fetolang.sebaka.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（异硫氰酸荧光光素（异硫氰酸荧光光素光荧光素光荧光光素（异硫氰酸荧光盐水(TBS)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-декстра = FITC-декстра = сти потока Q = 2400 мкм3/с Конические области микроканалов. Li-microgel li ile tsa kenngoa ha Tris buffered saline (TBS) e ne e tsoakoa le 0.1mg/mL (fluorescein isothiocyanate) FITC-dextran ho ΔP = 700 Pa (<ΔPtr) le sekhahla sa phallo Q = 2400 µm3/s Libaka tse Conical tsa li-microchannel.Boemo bo ka pele Xf ba microgel bo khetholla sebaka sa eona ho tloha sebakeng sa pele sa shrinkage X0.Ho kenya lysis, tharollo ea tPA e ngotsoeng ka fluorescently ho TBS e ile ea kenngoa ho tloha mocha o fumanehang ka orthogonally ho ea ho axis e telele ea microchannel e kholo.
Ha tharollo ea tPA e fihla ho occlusal MM, moeli o ka morao oa microgel o ile oa senyeha, o bontšang hore fibrin cleavage e qalile ka nako tlys = 0 (Fig. 3d le Supplementary Fig. 18).Nakong ea fibrinolysis, tPA e ngotsoeng ka dae e bokella ka hare ho MM ebe e tlama likhoele tsa fibrin, e leng se lebisang ho eketseha ha butle-butle ho matla a 'mala o pinki oa li-microgels.Ho tlys = 60 min, MM e etsa likonteraka ka lebaka la ho felisoa ha karolo ea eona e ka morao, 'me boemo ba eona bo ka pele ba Xf bo fetoha hanyane.Ka mor'a metsotso ea 160, MM e nang le konteraka e matla e ile ea tsoela pele ho etsa konteraka, 'me ka tlys = 161 min, e ile ea e-ba le konteraka, kahoo e tsosolosa phallo ea metsi ka microchannel (Fig. 3d le Supplementary Fig. 18, kholomo e nepahetseng).
Ka feiga.3e e bonts'a phokotseho e itšetlehileng ka nako ea lysis-mediated ea molumo V (tlys) e tloaelehileng ho ea pele ea V0 ea boholo bo fapaneng ba fibrin microgels.CO e nang le D0 174, 199, kapa 218 µm e ile ea kenngoa ka har'a mochine o monyenyane o nang le ΔP 1200, 1800, kapa 3000 Pa, ka ho latellana, le Q = 1860 ± 70 µm3/s ho thibela microchannel (Fig. 3e, inset).phepo e nepahetseng.Li-microgels li fokotseha butle-butle ho fihlela li le nyenyane ho lekana ho feta likanaleng.Ho fokotseha ha molumo oa bohlokoa oa CO ka bophara bo boholoanyane ba pele ho hloka nako e telele ea lysis.Ka lebaka la phallo e ts'oanang ka li-RM tsa boholo bo fapaneng, ho petsoha ho etsahala ka lebelo le ts'oanang, ho bakang tšilo ea likaroloana tse nyane tsa li-RM tse kholo le phetisetso ea tsona e liehang.Ka feiga.3f e bonts'a phokotso e lekanyelitsoeng ho V(tlys)/V0 ka lebaka la ho arohana ha SM, MM, le RM ho D0 = 197 ± 3 µm e reriloeng joalo ka ts'ebetso ea tlys.Bakeng sa SM, MM le RM, beha microgel ka 'ngoe ka har'a microchannel e nang le ΔP 400, 750 kapa 1800 Pa le Q 12300, 2400 kapa 1860 µm3/s, ka ho latellana.Le hoja khatello e sebelisoang ho SM e ne e le ka tlase ho makhetlo a 4.5 ho feta ea RM, phallo ea SM e ne e le matla ka makhetlo a fetang a tšeletseng ka lebaka la ho phunyeletsa ho phahameng ha SM, 'me ho fokotseha ha microgel ho ile ha fokotseha ho tloha ho SM ho ea ho MM le RM. .Ka mohlala, ho tlys = 78 min, SM e ile ea qhaloa haholo 'me ea falla, ha MM le PM ba ntse ba tsoela pele ho koala li-microchannels, ho sa tsotellehe ho boloka feela 16% le 20% ea molumo oa bona oa pele, ka ho latellana.Liphetho tsena li fana ka maikutlo a bohlokoa ba convection-mediated lysis ea constricted fibrous gels le ho amahanngoa le litlaleho tsa tšilo ea mali e potlakileng e nang le fibrin e tlase.
Ka hona, mosebetsi oa rona o bonts'a mokhoa oa liteko le oa theory oo li-gels tsa filamentous li arabelang ho koalloa ha biaxial.Boitšoaro ba li-gel tsa fibrous sebakeng se lekanyelitsoeng bo khethoa ke asymmetry e matla ea matla a matla a li-filaments (e bonolo ka ho hatella le ho thata ka tsitsipano) le feela ka karolo ea likarolo le ho kobeha ha likhoele.Boitšoaro bona bo fella ka bolelele bo fokolang ba li-gel tsa fibrous tse ka har'a li-capillaries tse moqotetsane, tekanyo ea tsona ea biaxial Poisson e fokotseha ka khatello e ntseng e eketseha le khatello e fokolang ea leseli.
Kaha ts'ebeliso ea biaxial ea likaroloana tse bonolo tse holofalang e sebelisoa mefuteng e mengata ea mahlale, liphetho tsa rona li hlohlelletsa nts'etsopele ea lisebelisoa tse ncha tsa fiber.Haholo-holo, ho bolokoa ha biaxial ea li-gel filamentous ka li-capillaries tse moqotetsane kapa li-tubes ho lebisa ho tšubuhlellano ea bona e matla le ho fokotseha ho hoholo ha ho khoneha.Thibelo e matla ea ho phalla ha mokelikeli ka li-gel tsa occlusive fibrous ho na le melemo ha e sebelisoa e le li-plug ho thibela mali kapa ho fokotsa phepelo ea mali ho malignancies33,34,35.Ka lehlakoreng le leng, ho fokotseha ha phallo ea mokelikeli ka gel ea occlusal fibrin, ka tsela eo ho thibela convective-mediated thrombus lysis, ho fana ka pontšo ea butle-butle lysis ea occlusal clots [27, 36, 37].Sistimi ea rona ea mohlala ke mohato oa pele oa ho utloisisa se boleloang ke karabelo ea mochini ea li-fibrous biopolymer hydrogels ho boloka biaxial.Ho kenyelletsa lisele tsa mali kapa li-platelet ho li-gels tsa fibrin tse thibelang ho tla ama boitšoaro ba bona ba thibelo 38 'me e tla ba mohato o latelang oa ho senola boitšoaro ba litsamaiso tse rarahaneng tsa biologically bohlokoa.
Li-reagents tse sebelisetsoang ho lokisa li-microgel tsa fibrin le ho etsa lisebelisoa tsa MF li hlalositsoe ho Boitsebiso bo Tlatselletsang (Mekhoa ea Tlatsetso Karolong ea 2 le ea 4).Li-microgels tsa Fibrin li ile tsa lokisoa ka ho etsa emulsifying tharollo e tsoakiloeng ea fibrinogen, Tris buffer le thrombin ka phallo e shebaneng le sesebelisoa sa MF, e lateloa ke marotholi a marotholi.Tharollo ea bovine fibrinogen (60 mg/ml ho TBS), Tris buffer le bovine thrombin solution (5 U/ml in 10 mM CaCl2 solution) li ile tsa tsamaisoa ho sebelisoa lipompo tse peli tsa seringe tse laoloang ka boikemelo (PhD 200 Harvard Apparatus PHD 2000 Syring Pump).ho thibela MF, USA).Mokhahlelo o tsoelang pele oa F-oli o nang le 1 wt.% block copolymer PFPE-P(EO-PO)-PFPE, o ile oa kenngoa yuniti ea MF ho sebelisoa pompo ea seringe ea boraro.Marotholi a entsoeng ka mochine oa MF a bokelloa ka 15 ml centrifuge tube e nang le F-oli.Beha liphaephe ka bateng ea metsi ka 37 °C bakeng sa 1 h ho tlatsa fibrin gelation.FITC e ngotsoeng fibrin microgels e lokisitsoe ka ho tsoaka bovine fibrinogen le FITC e ngotsoeng human fibrinogen ka tekanyo ea boima ba 33:1, ka ho latellana.Mokhoa ona o tšoana le oa ho lokisoa ha fibrin microgels.
Fetisetsa li-microgels ho tloha ho oli F ho ea ho TBS ka centrifuging ho qhalakanngoa ho 185 g bakeng sa 2 min.Li-microgels tse nang le metsi li ile tsa qhalakanngoa ka oli F e kopantsoeng le 20 wt.% perfluorooctyl alcohol, eaba ea hasanngoa ka hexane e nang le 0.5 wt.% Span 80, hexane, 0.1 wt.% Triton X metsing le TBS.Qetellong, li-microgel li ile tsa qhalakanngoa ho TBS e nang le 0.01 wt% Pakeng tsa 20 'me tsa bolokoa ho 4 ° C bakeng sa libeke tse ka bang 1-2 pele ho liteko.
Ho etsoa ha sesebelisoa sa MF ho hlalositsoe ho Tlhahisoleseding ea Tlatsetso (Mekhoa ea Tlatsetso Karolo ea 5).Tekong e tloaelehileng, boleng bo botle ba ΔP bo khethoa ke bophahamo bo lekanang ba matamo a hokahaneng pele le ka morao ho sesebelisoa sa MF bakeng sa ho hlahisa li-microgel tse bophara ba 150
Lintlha tse tšehetsang liphetho tsa phuputso ena li fumaneha ho tsoa ho bangoli ba fapaneng ha ba li kopa.Litšoantšo tsa SEM tse tala tsa li-gel tsa fibrin, litšoantšo tse tala tsa TEM tsa li-gel tsa fibrin pele le ka mor'a ho kenngoa, le lintlha tse ka sehloohong tsa ho kenya litšoantšo tsa 1 le 2. 2 le 3 li fanoa ka faele ea data e tala.Sengoliloeng sena se fana ka lintlha tsa mantlha.
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