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Mmachi nke hydrogels fibrous na capillaries warara dị oke mkpa na usoro ndu na usoro ndu.A mụọla mgbakasị ahụ na mkpakọ uniaxial nke fibrous hydrogels nke ọma, mana nzaghachi ha na njide biaxial na capillaries ka achọpụtabeghị.N'ebe a, anyị na-egosipụta nnwale na n'ụzọ doro anya na gels filamentous na-anabata qualitatively dị iche iche na-egbochi mmachi karịa mgbanaka yinye gels n'ihi asymmetry na n'ibu Njirimara nke connstituent filaments, nke dị nro na mkpakọ na stiif na esemokwu.N'okpuru njide siri ike, gel fibrous na-egosipụta ntakịrị elongation yana mbelata asymptotic na biaxial Poisson's ratio na efu, na-ebute mkpokọta gel siri ike na mmịnye mmiri na-adịghị mma site na gel.Nsonaazụ ndị a na-egosi nguzogide nke agbatị occlusive thrombi na lysis site n'aka ndị na-agwọ ọrịa ma na-akpali mmepe nke endovascular embolization dị irè site na gels fibrous iji kwụsị ọbara ọgbụgba vaskụla ma ọ bụ gbochie ọbara ọgbụgba nke etuto ahụ.
Netwọk fibrous bụ ntọala ntọala na arụrụ ọrụ nke anụ ahụ na sel dị ndụ.Actin bụ akụkụ bụ isi nke cytoskeleton1;fibrin bụ ihe dị mkpa na ọgwụgwọ ọnya na thrombus formation2, na collagen, elastin na fibronectin bụ akụkụ nke matrix extracellular na alaeze anụmanụ3.Netwọk eweghachitere nke fibrous biopolymers abụrụla ihe nwere nnukwu ngwa na injinị anụ ahụ4.
Netwọk filamentous na-anọchi anya klaasị dị iche iche nke ihe dị nro dị ndụ nwere ihe eji arụ ọrụ dị iche na netwọkụ molekụla na-agbanwe agbanwe5.Ụfọdụ n'ime ihe ndị a etolitela n'oge evolushọn iji chịkwaa nzaghachi nke ihe ndị dị ndụ na deformation6.Dịka ọmụmaatụ, netwọk fibrous na-egosi ngbanwe ahịrị na obere eriri7,8 ebe na nnukwu nsogbu ha na-egosipụta nkwụsi ike dị elu9,10, si otú a na-edobe iguzosi ike n'ezi anụ ahụ.Achọpụtabeghị ihe ọ pụtara maka ihe ndị ọzọ na-arụ ọrụ nke fibrous gels, dị ka nrụgide nkịtị na-adịghị mma na nzaghachi na nsogbu shiee11,12, ka achọpụtabeghị.
A mụọla ihe eji arụ ọrụ nke hydrogels fibrous na-agbanwe agbanwe n'okpuru uniaxial tension13,14 na compression8,15, mana a mụọbeghị mpịakọta biaxial nke nnwere onwe na-akpata na capillaries ma ọ bụ tubes dị warara.N'ebe a, anyị na-akọpụta nsonaazụ nnwale ma na-atụ aro usoro maka omume nke fibrous hydrogels n'okpuru njigide biaxial na ọwa microfluidic.
Fibrin microgels nwere oke dị iche iche nke fibrinogen na mkpokọta thrombin yana dayameta D0 sitere na 150 ruo 220 µm site na iji usoro microfluidic (Ntinye mgbakwunye 1).Na fig.1a na-egosi onyonyo nke fluorochrome akpọrọ microgels enwetara site na iji confocal fluorescence microscopy (CFM).Microgels ndị ahụ dị okirikiri, nwere polydispersity nke na-erughị 5%, ma bụrụ otu n'usoro n'ofe akpịrịkpa nke CFM (ozi mgbakwunye na ihe nkiri S1 na S2) nyochara.Nkezi pore nke microgels (ekpebisiri ike site na ịlele Darcy permeability16) si na 2280 ruo 60 nm, ọdịnaya fibrin mụbara site na 5.25 ruo 37.9 mg / ml, na mkpokọta thrombin belatara site na 2.56 ruo 0.27 nkeji / mL, n'otu n'otu.(Ozi Mgbakwunye).Osikapa.2), 3 na tebụl mgbakwunye 1).Nkwụsi ike kwekọrọ na microgel na-abawanye site na 0.85 ruo 3.6 kPa (Mgbakwunye 4).Dị ka ihe atụ nke gels nke e si na agbụ na-agbanwe agbanwe, a na-eji agarose microgels nke isi ike dị iche iche.
Ihe onyonyo nke fluorescence microscopy nke fluorescein isothiocyanate (FITC) akpọrọ PM kwụsịtụrụ na TBS.Ọnụ ọgụgụ mmanya bụ 500 µm.b foto SEM nke SM (n'elu) na RM (n'okpuru).Ogwe ọnụ ọgụgụ 500 nm.c Eserese eserese nke ọwa microfluidic nke nwere nnukwu ọwa (dayameta dl) na mpaghara nwere ụdị cone nwere warara nwere akụkụ ntinye α nke 15° na dayameta nke dc = 65 µm.d aka ekpe gaa n'aka nri: Onyonyo microscope anya nke RM (dayameta D0) na nnukwu ọwa, mpaghara conical na mgbochi (mmachi ogologo gel Dz).Ọnụ ọgụgụ mmanya bụ 100 µm.e, f TEM oyiyi nke RM na-adịghị edozi (e) na RM (f) na-ekpuchighị , edozi maka otu awa na nkwụsịtụ 1 / λr = 2.7, na-esote ntọhapụ na nhazi nke 5% nke oke.Glutaraldehyde na TBS.The dayameta nke undeformed CO bụ 176 μm.Ogwe ọnụ ọgụgụ dị 100 nm.
Anyị lekwasịrị anya na microgels fibrin nwere ike nke 0.85, 1.87 na 3.6 kPa (nke a na-akpọ microgels soft (SM), microgels siri ike (MM) na microgels siri ike (RM), n'otu n'otu).Nke a dị iche iche nke fibrin gel isi ike bụ otu usoro nke ịdị ukwuu dị ka mkpirisi ọbara18,19 ya mere, fibrin gels nke a na-amụ n'ọrụ anyị na-emetụta kpọmkwem usoro ndu ndu.Na fig.1b na-egosi onyonyo elu na ala nke ihe owuwu SM na RM enwetara site na iji nyocha eletrọnịkị nyocha (SEM), n'otu n'otu.E jiri ya tụnyere usoro RM, netwọk SM na-etolite site na eriri ndị buru ibu na isi alaka dị ole na ole, kwekọrọ na akụkọ mbụ 20, 21 (Fig 5 nke mgbakwunye).Ihe dị iche na nhazi nke hydrogel na-ejikọta ya na omume nke ihe onwunwe ya: njedebe nke gel na-ebelata site na mbelata pore size site na SM ruo MM na RM (Mgbakwunye Tebụl 1), na isi ike nke gel na-atụgharị.Achọpụtaghị mgbanwe na nhazi microgel mgbe nchekwa na 4 Celsius C maka ụbọchị 30 (Mgbakwunye Fig. 6).
Na fig.1c na-egosi eserese nke ọwa microfluidic nke nwere akụkụ okirikiri okirikiri nwere (site n'aka ekpe gaa n'aka nri): nnukwu ọwa nwere dayameta dl nke microgel na-anọgide na-agbanweghị agbanwe, akụkụ cone nwere nke na-ebelata na dayameta dc
Na fig.1e.Mgbe mkpakọ RM gasịrị, microgel pore size na-ebelata nke ukwuu na ọdịdị ha ghọrọ anisotropic na obere nha na ntụziaka nke mkpakọ, nke kwekọrọ na akụkọ mbụ 23.
Mkpakọ biaxial n'oge nkwekọrịta na-eme ka microgel gbatịa n'ụzọ na-akparaghị ókè yana ọnụọgụ ọnụọgụ λz = \({D}_{{{{{{\rm{z}}}}}}}}}/\({D }_ { 0}\), ebe \({D}_{{{{({\rm{z}}}}}}}}\)) bụ ogologo nke microgel mechiri emechi Foto 2a na-egosi mgbanwe na λzvs .1/ λr N'ụzọ dị ịtụnanya, n'okpuru mkpakọ siri ike nke 2.4 ≤ 1 / λr ≤ 4.2, fibrin microgels na-egosi elongation na-adịghị mma nke 1.12 +/- 0.03 λz, nke na-emetụta naanị uru nke 1 / λr. obere agarose microgels, nke a na-ahụta ọbụna na mkpakọ adịghị ike 1 / λr = 2.6 na elongation buru ibu λz = 1.3.
a Agarose microgel nnwale na dị iche iche na-agbanwe moduli (2.6 kPa, green oghe diamond; 8.3 kPa, agba aja aja oghe okirikiri; 12.5 kPa, oroma na-emeghe square; 20.2 kPa, magenta na-emeghe inverted triangle) na SM ( siri ike red) Gbanwee na atụ elongation λz ( okirikiri), MM ( square ojii siri ike) na RM (triangles na-acha anụnụ anụnụ).Ahịrị siri ike na-egosi amụma amụma λz maka agarose (akara ndụ ndụ) na fibrin microgels (ahịrị na akara nke otu agba).b, c Top panel: schematic diagram of network chains of agarose (b) na fibrin (c) tupu (aka ekpe) na mgbe (n'aka nri) biaxial mkpakọ.N'okpuru: Ọdịdị nke netwọk kwekọrọ tupu na mgbe nrụrụ.A na-egosi ntụzịaka mkpakọ x na y site na magenta na akụ aja aja, n'otu n'otu.N'ọnụọgụgụ dị n'elu, a na-egosi ụdọ netwọk ndị gbadoro ụkwụ na ntụzịaka x na y ndị a nwere ahịrị magenta na agba aja aja dabara adaba, na agbụ ndụ akwụkwọ ndụ na-anọchi anya agbụ nke dabere na ntụzịaka z aka ike.Na fibrin gel (c), ahịrị na-acha odo odo na agba aja aja na ntụzịaka x na y na-ehulata karịa ka ọ dị na steeti na-adịghị edozi, na ahịrị akwụkwọ ndụ akwụkwọ ndụ na ntụziaka z na-ehulata ma gbatịa.A na-ebufe esemokwu n'etiti ntụzịaka nke mkpakọ na esemokwu site na eriri nwere ntụzịaka etiti.Na gels agarose, agbụ n'akụkụ niile na-ekpebi nrụgide osmotic, nke na-enye aka dị ukwuu na nrụrụ nke gel.d Mgbanwe amụma na oke biaxial Poisson, } } ^ {{{{\rm{eff}}}}}} =-{{{{{\rm{ln}}}}}} {\lambda }_{ z}/{{{{ {{ \rm{ln}}}}}}} {\lambda }_{r}\ , maka mkpakọ nke agarose (akara ndụ ndụ) na fibrin (akara uhie).Ihe ntinye na-egosi nrụrụ biaxial nke gel.e Mgbanwe mgbanwe mgbanwe ΔPtr, nke a na-eme ka ọ bụrụ gel stiffness S, bụ nke a na-eme atụmatụ dị ka ọrụ nke mkpakọ maka agarose na fibrin microgels.Agba akara kwekọrọ na agba dị na (a).Ahịrị akwụkwọ ndụ akwụkwọ ndụ na-acha uhie uhie na-egosi mmekọrịta dị n'etiti ΔPtr/S na 1/λr maka agarose na fibrin gels, n'otu n'otu.Akụkụ a gbajiri agbaji nke ahịrị uhie na-egosi mmụba na ΔPtr n'okpuru mkpakọ siri ike n'ihi mmekọrịta interfiber.
A na-ejikọta ọdịiche a na usoro dị iche iche nke nrụrụ nke fibrin na agarose microgel netwọk, nke nwere mgbanwe 24 na eriri 25 siri ike, n'otu n'otu.Mkpokọta biaxial nke gels na-agbanwe agbanwe na-eduga na mbelata nke olu ha na mmụba jikọtara ya na ntinye uche na nrụgide osmotic, nke na-eduga na elongation nke gel na ntụziaka na-akparaghị ókè.Ngwunye ikpeazụ nke gel na-adabere na nguzozi nke mmụba nke ike n'efu nke entropic nke agbụ a na-agbatị na mbelata nke ike n'efu nke osmosis n'ihi ntanye polymer dị ala na gel gbatịa.N'okpuru mkpakọ biaxial siri ike, elongation nke gel na-abawanye na λz ≈ 0.6 \({{\lambda}_{{{\rm{r}}}}^{-2/3}}) (lee Fig. 2a na ngalaba mkparịta ụka 5.3.3).Mgbanwe mgbanwe na agbụ na-agbanwe agbanwe na ọdịdị nke netwọk kwekọrọ tupu na mgbe ejiri biaxial na-egosi na fig.2b.
N'ụzọ dị iche, gels fibrous dị ka fibrin na-emeghachi omume n'ụzọ dị iche na njigide biaxial.The filaments gbakwasara predominantly yiri ntụzịaka nke mkpakọ flex (si otú ibelata anya n'etiti cross-njikọ), mgbe filaments predominantly perpendicular na ntụziaka nke mkpakọ gbatịa ma gbatịa n'okpuru omume nke na-agbanwe ike, na-eme ka jel elongate ( Foto 1).2c) Ihe e ji mara ihe owuwu nke SM, MM na RM na-emeghị nke ọma site n'ịtụle onyonyo SEM na CFM ha (Ngalaba mkparịta ụka mgbakwunye IV na eserese 9).Site n'ịchọpụta modulus na-agbanwe (E), dayameta (d), ogologo profaịlụ (R0), anya n'etiti nsọtụ (L0 ≈ R0) na etiti etiti (ψ0) nke strands na microgels fibrin na-adịghị edozi (Nkwupụta 2) - 4), anyị na-ahụ na eri na-ehulata modulus \({k}_{{{{{{\rm{b)))))))))}=\frac{9\pi E{d}^{4} } {4 {\psi } _{0}^{2}{L}_{0}}\) dị obere karia modul tensile ya ({k}_{{{{{{{\rm{s}}}}}) }} }}=E\frac{\pi {d}^{2}{R}_{0}}{4}\), so kb/ks ≈ 0.1 (Mgbakwunye Tebụl 4).Ya mere, n'okpuru ọnọdụ nke njide biaxial gel, eriri fibrin na-ehulata ngwa ngwa, ma na-eguzogide ịgbatị.E gosipụtara elongation nke netwọk filamentous nke etinyere na mkpakọ biaxial na Fig. 17.
Anyị na-emepụta ihe atụ affine usoro (Nkwukọrịta Mgbakwụnye Nkebi V na Ọnụ Ọgụgụ 10-16) nke a na-ekpebi elongation nke gel fibrous site na nha nha mpaghara nke ndị na-agbanwe ike na-arụ ọrụ na gel ma buru amụma na n'ime nsogbu biaxial siri ike λz - 1 n'okpuru mmachi
Nhazi (1) na-egosi na ọbụlagodi n'okpuru mkpakọ siri ike (\({\lambda }_{{\mbox{r))))\,\to \,0\)) enwere ntakịrị mmụba gel na nrụrụ elongation na-esote. saturation λz–1 = 0.15 ± 0.05.Omume a metụtara (i) \({\ekpe({k}_{{{{{\rm{b}}}}}}}}/{k}_{{{{{\rm} {s }}}}}}\nri)}^{1/2}\) ≈ 0.15−0.4 na (ii) okwu ahụ dị n'ụba brackets square asymptotically approximates \(1{{\mbox{/}}} \sqrt {3}\) maka njikọ nke biaxial siri ike. Ọ dị mkpa iburu n'uche na prefactor \({\ left({k}_{({\mbox{b)))))/{k}_{({\mbox{ s))))\right)}^{1/ 2}\) enweghị ihe jikọrọ ya na isi ike nke eriri E, mana a na-ekpebi ya naanị site na akụkụ nke eriri d/L0 na akụkụ etiti nke arc. ψ0, nke yiri SM, MM na RM (Table 4).
Iji mee ka ọ pụta ìhè n'ọdịiche dị n'ụdị nnwere onwe na-ebute n'etiti gels na-agbanwe na filamentous, anyị na-ewebata nhazi nke biaxial Poisson \({\nu }_{{{({\rm{b)))))) }{{\ mbox { =}}}\,\mathop{{\lim}}\limit_{{\lambda}_{{{{({\rm{r}}}}}}\to 1}\ frac{{\ lambda } _{ {{{\rm{z}}}}}}}-1}{1-{\lambda }_{{({\rm{r}}}}}}}}, \) na-akọwa enweghị oke nghazi nke eriri gel na nzaghachi maka nha nha nha n'akụkụ ụzọ radial abụọ, wee gbasaa nke a ruo nnukwu ụdị ụdị \ rm{b}}}}}}}} ^ {{{{{\rm{eff}}}}}} }}=-{{{{{\rm{ln}}}}}}} }{ \lambda } _{z} /{{({\rm{ln)))))))}{\lambda }_{{({\rm{r)))))))}\) .Na fig.2d egosi \({{{{{\rm{\nu }}}}}}_{{{\rm{b}}}}}}}}^{{{{\rm { eff }}}}}}}\) maka mkpakọ biaxial otu nke mgbanwe (dị ka agarose) na nke siri ike (dị ka fibrin) gels (Mkparịta ụka mgbakwunye, Nkebi 5.3.4), ma gosipụta mmekọrịta dị n'etiti ndịiche siri ike na nzaghachi na njide. Maka agarose gels n'okpuru mgbochi siri ike {\rm{eff}}}}}}}\) na-abawanye na uru asymptotic 2/3, na maka fibrin gels ọ na-agbada na efu, ebe ọ bụ na lnλz/lnλr → 0, ebe λz na-abawanye na saturation ka λr na-abawanye.Rịba ama na na nnwale, microgels sppherical mechiri emechi na-emebi inhomogeneously, na akụkụ etiti ha na-enweta mkpakọ siri ike karị;Otú ọ dị, extrapolation na nnukwu uru nke 1 / λr na-eme ka o kwe omume iji nnwale ahụ tụnyere echiche maka gels nwere nkwarụ.
Achọpụtara ọdịiche ọzọ na omume nke gels yinye na-agbanwe agbanwe na gels filamentous n'ihi mmegharị ha n'elu nkwekọrịta.Nrụgharị ntụgharị ΔPtr, nke a na-eme ka ọ bụrụ gel stiffness S, na-abawanye na mkpakọ na-arịwanye elu (Fig 2e), ma na 2.0 ≤ 1 / λr ≤ 3.5, fibrin microgels gosipụtara ụkpụrụ dị ala nke ΔPtr / S ala n'oge nkwụsị.Njide nke microgel agarose na-eduga n'ịbawanye nrụgide osmotic, nke na-eduga n'ịgbatị gel na ntụziaka ogologo oge ka a na-agbatị molekul polymer (Fig 2b, ekpe) na mmụba nke ntụgharị ntụgharị site na ΔPtr / S ~ (Fig. 1/r) 14/317.N'ụzọ megidere nke ahụ, a na-ekpebi ọdịdị nke microgels fibrin mechiri emechi site na nguzozi ike nke eriri nke mkpakọ radial na esemokwu ogologo oge, nke na-eduga na nrụrụ ogologo ogologo oge λz ~\(\sqrt{{k}_{{{{{{{{{{}}}}}} \rm{b))))))))} /{k}_{{{{{\rm{s}}}}}}}\).Maka 1/λr ≫ 1, a na-eme mgbanwe na nrụgide ntụgharị asụsụ ka 1 }{{{({\rm{ln)))))\ekpe({{\lambda }}_{{{{\rm} {r} }}}}}}^{-} 1} \n'aka nri)\) (Mkparịta ụka mgbakwunye, Nkeji 5.4), dị ka e gosiri site n'ahịrị uhie siri ike na Fig. 2e.Ya mere, ΔPtr dị obere karịa na gels agarose.N'ihi na compressions na 1 / λr> 3.5, a ịrịba abawanye na olu nke nta nke nta nke filaments na mmekọrịta nke agbata obi filaments ókè n'ihu deformation nke gel na-eduga na deviations nke ibuo pụta si amụma (red dotted akara na fig. 2e).Anyị kwubiri na maka otu 1/λr na Δ\({P}_{{{{{\rm{tr}}}}}}}}_{{{{\rm{fibrin}}}))) } }}}\) < ΔP < Δ\({P}_{{{{{\rm{tr)))))))}}_{{{{\rm{agarose}}}} } } }}\) a ga-ejide agarose gel site na microchannel, na fibrin gel nwere otu isi ike ga-agafe na ya.Maka ΔP < Δ\({P}_{{{{{{\rm{tr))))))))_{{{{\rm{fibrin)))))))))}\ ), Gel abụọ abụọ ga-egbochi ọwa ahụ, ma fibrin gel ga-agbanyekwu nke ọma ma na-agbakọ nke ọma, na-egbochi mmiri na-asọba nke ọma.Nsonaazụ egosipụtara na eserese 2 na-egosi na gel fibrous nwere ike ije ozi dị ka plọg dị irè iji belata ọbara ọgbụgba ma ọ bụ gbochie inye ọbara na etuto ahụ.
N'aka nke ọzọ, fibrin na-emepụta ihe nkedo nke na-eduga na thromboembolism, ọnọdụ pathological nke thrombus na-ekpuchi arịa na ΔP <ΔPtr, dị ka ụfọdụ ụdị ọrịa strok ischemic (Fig 3a).Mgbochi na-esighị ike na-akpata elongation nke fibrin microgels mere ka mmụba dị ike na fibrin ntinye nke C / C fibrinogen ma e jiri ya tụnyere gels na-agbanwe agbanwe, ebe C na C fibrinogen na-amachibidoro na microgels na-adịghị edozi, n'otu n'otu.Ntinye uche polymer n'ime gel.Ọnụ ọgụgụ 3b na-egosi na fibrinogen C / C na SM, MM, na RM mụbara karịa okpukpu asaa na 1 / λr ≈ 4.0, na-akpali site na mmachi na akpịrị ịkpọ nkụ (Mgbakwunye 16).
Nleta atụmatụ nke mgbachi nke akwara etiti ụbụrụ n'ụbụrụ.b Mmụba n'ihe gbasara mmachi nke fibrin na SM obstructive ( okirikiri uhie siri ike), MM ( square ojii siri ike), na RM (triangles na-acha anụnụ anụnụ siri ike).c Nnwale eji amụ nwapu nke gels fibrin amachibidoro.Ngwọta nke tPA a na-akpọ fluorescently na TBS ka agbanyere n'ọsọ ọsọ nke 5.6 × 107 µm3/s yana mgbada nrụgide ọzọ nke 0.7 Pa maka ọwa dị n'akụkụ ogologo axis nke microchannel isi.d Pooled multichannel microscopic oyiyi nke obstructive MM (D0 = 200 µm) na Xf = 28 µm, ΔP = 700 Pa na n'oge nkewa.Ahịrị ntụpọ kwụ ọtọ na-egosi ọnọdụ mbụ nke azụ azụ na ihu ihu nke MM na tlys = 0. Agba ndụ ndụ na pink kwekọrọ FITC-dextran (70 kDa) na tPA nke akpọrọ AlexaFluor633, n'otu n'otu.e Ogologo oge dị iche iche nke RM nwere D0 nke 174 µm (triangle na-acha anụnụ anụnụ), 199 µm (triangle na-acha anụnụ anụnụ), na 218 µm (triangle na-acha anụnụ anụnụ), n'otu n'otu, na microchannel conical nwere Xf = 28 ± 1 µm.Akụkụ ndị ahụ nwere ΔP 1200, 1800, na 3000 Pa, n'otu n'otu, na Q = 1860 ± 70 µm3 / s.Ihe ntinye na-egosi RM (D0 = 218 µm) na-agbanye microchannel.f Mgbanwe oge nke olu ikwu nke SM, MM ma ọ bụ RM etinye na Xf = 32 ± 12 µm, na ΔP 400, 750 na 1800 Pa na ΔP 12300 Pa na Q 12300 na mpaghara conical nke microchannel, n'otu n'otu 2400 na 1800 µm3. /s.Xf na-anọchi anya ọnọdụ ihu nke microgel ma chọpụta ebe dị anya site na mmalite nke mbelata.V(tlys) na V0 bụ olu nwa oge nke microgel lysed na olu nke microgel na-enweghị nsogbu, n'otu n'otu.Agba agwa kwekọrọ na agba dị na b.Akụ ojii na e, f kwekọrọ na oge ikpeazụ tupu microgels gafere microchannel.Ogwe ọnụ ọgụgụ dị na d, e bụ 100µm.
Iji nyochaa mmetụta nke mmachi na mbelata mmiri na-erugharị n'ofe gels obstructive fibrin, anyị mụrụ lysis nke SM, MM, na RM na thrombolytic agent tissue plasminogen activator (tPA).Ọnụọgụ 3c na-egosi nhazi nnwale ejiri mee nyocha lysis. Na ΔP = 700 Pa (<ΔPtr) na ọnụ ọgụgụ na-asọpụta, Q = 2400 μm3 / s, nke Tris-buffered saline (TBS) jikọtara ya na 0.1 mg / mL nke (fluorescein isothiocyanate) FITC-Dextran, microgel kpuchiri microchannel tapered. mpaghara. Na ΔP = 700 Pa (<ΔPtr) na ọnụ ọgụgụ na-asọpụta, Q = 2400 μm3 / s, nke Tris-buffered saline (TBS) jikọtara ya na 0.1 mg / mL nke (fluorescein isothiocyanate) FITC-Dextran, microgel kpuchiri microchannel tapered. mpaghara. При ΔP = 700 Па (<ΔPtr) na скорости потока, Q = 2400 мкм3/с сцеинизотиоцианата) FITC-декстрана, микрогель перекрывал сужающийся микроканал. Na ΔP = 700 Pa (<ΔPtr) na ọsọ ọsọ, Q = 2400 µm3 / s, nke Tris buffered saline (TBS) jikọtara ya na 0.1 mg / mL (fluorescein isothiocyanate) FITC-dextran, microgel kpuchiri microchannel na-ejikọta ọnụ.mpaghara.在ΔP = 700 Pa (<ΔPtr) 和流速Q = 2400 μm3/s 的Tris 缓冲盐水(TBS) 与0.1 mg/mL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) при ΔP = 700 Па (<ΔPtr) na скорости потока Q = 2400 мкм3/с Конические области микроканалов. Microgels kwadoro mgbe Tris buffered saline (TBS) jikọtara ya na 0.1mg/mL (fluorescein isothiocyanate) FITC-dextran na ΔP = 700 Pa (<ΔPtr) na ọnụego Q = 2400 µm3 / s Conical mpaghara nke microchannels.Ọkwa n'ihu Xf nke microgel na-ekpebi ịdị anya ya site na ebe mgbaba mbụ X0.Iji kpalite lysis, ihe ngwọta nke tPA nke a na-akpọ fluorescently na TBS ka agbanyere site na ọwa nke dị n'usoro gaa na ogologo axis nke microchannel bụ isi.
Mgbe ihe ngwọta tPA rutere MM occlusal, akụkụ azụ nke microgel ahụ bịara na-agbaji, na-egosi na nkwụsị nke fibrin amalitela n'oge tlys = 0 (Fig 3d na Fig. 18).N'oge fibrinolysis, tPA nke e ji esiji mee na-agbakọta n'ime MM wee jikọta eriri fibrin, nke na-eduga n'ịbawanye nwayọọ nwayọọ na agba pink nke microgels.Na tlys = 60 min, MM nkwekọrịta n'ihi mgbasa nke akụkụ azụ ya, na ọnọdụ nke isi ihu Xf na-agbanwe ntakịrị.Mgbe 160 min, MM siri ike na-aga n'ihu na-aga n'ihu na nkwekọrịta, na tlys = 161 min, ọ na-enwe nkwekọrịta, si otú ahụ na-eweghachi mmiri na-asọba site na microchannel (Fig. 3d na Mgbakwunye 18, kọlụm aka nri).
Na fig.3e na-egosi mbelata oge na-adabere na lysis na-adabere na olu V (tlys) na-ahazi na olu mbụ V0 nke microgels fibrin dị iche iche.A na-etinye CO na D0 174, 199, ma ọ bụ 218 µm n'ime microchannel na ΔP 1200, 1800, ma ọ bụ 3000 Pa, n'otu n'otu, na Q = 1860 ± 70 µm3 / s iji gbochie microchannel (Fig 3e, inset).oriri na-edozi ahụ.Microgels ndị ahụ na-eji nwayọọ nwayọọ na-adalata ruo mgbe ha dị ntakịrị iji gafee ọwa.Mbelata olu dị oke egwu nke CO nwere dayameta mmalite ka ukwuu chọrọ ogologo oge lysis.N'ihi nrịbama yiri nke ahụ site na RM dị iche iche, nkwụsịtụ na-eme n'otu ọnụego ahụ, na-ebute mgbaze nke obere akụkụ nke RM buru ibu na ntụgharị ha na-egbu oge.Na fig.3f na-egosi mbelata ikwu na V (tlys)/V0 n'ihi nkewa maka SM, MM, na RM na D0 = 197 ± 3 µm kpara nkata dị ka ọrụ nke tlys.Maka SM, MM na RM, tinye microgel ọ bụla na microchannel nwere ΔP 400, 750 ma ọ bụ 1800 Pa na Q 12300, 2400 ma ọ bụ 1860 µm3/s, n'otu n'otu.Ọ bụ ezie na nrụgide a na-etinye na SM bụ 4.5 ugboro dị ala karịa nke RM, ntinye site na SM dị ike karịa ugboro isii n'ihi ike dị elu nke SM, na shrinkage nke microgel na-ebelata site na SM ruo MM na RM. .Dịka ọmụmaatụ, na tlys = 78 min, SM kacha gbasasịa ma chụpụ ya, ebe MM na PM gara n'ihu na-emechi microchannels, n'agbanyeghị na-ejigide naanị 16% na 20% nke olu mbụ ha, n'otu n'otu.Nsonaazụ ndị a na-egosi mkpa ọ dị n'usoro mgbasa ozi convection nke gels fibrous constricted ma jikọta ya na akụkọ banyere mgbaze ngwa ngwa nke mkpịsị na ọdịnaya fibrin dị ala.
Ya mere, ọrụ anyị na-egosipụta n'ụzọ nnwale na usoro usoro nke gels filamentous na-anabata njide biaxial.A na-ekpebi omume nke gels fibrous na oghere dị oke site na asymmetry siri ike nke ike ike nke filaments (dị nro na mkpakọ na ike na esemokwu) na naanị site n'akụkụ akụkụ na curvature nke filaments.Mmeghachi omume a na-ebute ntakịrị elongation nke fibrous gels dị na capillaries dị warara, nha biaxial Poisson na-ebelata site na mkpakọ na-abawanye na obere obere nrụgide.
Ebe ọ bụ na a na-eji njide biaxial nke ụmụ irighiri ihe na-eme ka ọ dị nro mee ihe na teknụzụ dị iche iche, nsonaazụ anyị na-akpali mmepụta nke ihe ọhụrụ fibrous.Karịsịa, njigide biaxial nke gels filamentous na capillaries ma ọ bụ tubes dị warara na-eduga ná mkpụkọ ha siri ike na mbelata dị ukwuu na permeability.Mgbochi siri ike nke mmiri na-asọba site na gels occlusive fibrous gels nwere uru mgbe ejiri ya dị ka plọg iji gbochie ọbara ọgbụgba ma ọ bụ belata ọbara na-ebute ọrịa 33,34,35.N'aka nke ọzọ, mbelata nke mmiri na-asọ site na occlusal fibrin gel, si otú a na-egbochi convective-mediated thrombus lysis, na-enye ihe ngosi nke ngwa ngwa lysis nke occlusal clots [27, 36, 37].Usoro ihe nlere anya anyị bụ nzọụkwụ mbụ n'ịghọta nsonaazụ nke nzaghachi igwe nke fibrous biopolymer hydrogels na njigide biaxial.Ịgbakwunye mkpụrụ ndụ ọbara ma ọ bụ platelet n'ime gels na-egbochi fibrin ga-emetụta omume mmachi ha 38 ma bụrụ nzọụkwụ ọzọ n'ikpughe omume nke sistemu dị mgbagwoju anya nke usoro ndu.
A na-akọwa ihe ndị a na-eji akwadebe microgels fibrin na imepụta ngwaọrụ MF na Ozi Mgbakwụnye (Usoro mgbakwunye Nkeji 2 na 4).A kwadebere microgels nke Fibrin site na emulsifying ngwakọta agwakọta nke fibrinogen, Tris buffer na thrombin n'ime ngwaọrụ MF na-eru eru, na-esote gelation droplet.Bovine fibrinogen solution (60 mg/ml na TBS), Tris buffer na bovine thrombin solution (5 U/ml na 10 mM CaCl2 solution) na-eji nfuli sirinji abụọ na-achịkwa onwe ha (PhD 200 Harvard Apparatus PHD 2000 Syring Pump).iji gbochie MF, USA).F-mmanụ na-aga n'ihu na-enwe 1 wt.% ngọngọ copolymer PFPE-P(EO-PO) -PFPE, ka ewebatara n'ime ngalaba MF site na iji mgbapụta sirinji nke atọ.A na-anakọta ụmụ irighiri mmiri etolite na ngwaọrụ MF n'ime tube centrifuge 15 ml nwere F-mmanụ.Tinye tubes n'ime mmiri ịsa ahụ na 37 Celsius C maka 1 h iji mezue gelation fibrin.A kwadebere FITC nke akpọrọ fibrin microgels site na ịgwakọta fibrinogen bovine na FITC akpọrọ fibrinogen mmadụ n'ogo 33: 1, n'otu n'otu.Usoro a bụ otu maka nkwadebe nke microgels fibrin.
Nyefee microgels site na mmanụ F na TBS site na ịgbasa mgbasa na 185 g maka 2 min.A na-achụsasị microgels ndị a na-agbanye ọkụ na mmanụ F gwakọtara ya na mmanya 20 wt.% perfluorooctyl, wee gbasaa na hexane nwere 0.5 wt.% Span 80, hexane, 0.1 wt.% Triton X na mmiri na TBS.N'ikpeazụ, a chụsasịrị microgels na TBS nwere 0.01 wt% Tween 20 ma chekwaa ya na 4 Celsius C maka ihe dịka 1-2 izu tupu nnwale.
A kọwapụtara nrụpụta ngwaọrụ MF na Ozi Mgbakwụnye (Usoro mgbakwunye Nkebi 5).N'ime nnwale a na-ahụkarị, a na-ekpebi uru dị mma nke ΔP site na ịdị elu dị elu nke ọdọ mmiri ndị ejikọtara tupu na mgbe ngwaọrụ MF maka iwebata microgels na dayameta nke 150
Data na-akwado nsonaazụ ọmụmụ a dị site n'aka ndị edemede dị iche iche mgbe a rịọrọ ya.Ihe oyiyi SEM Raw nke fibrin gels, ihe oyiyi TEM raw nke fibrin gels tupu na mgbe emechara ya, na isi ihe ntinye data maka ọnụọgụ 1 na 2. 2 na 3 na-enye na faịlụ data raw.Edemede a na-enye data izizi.
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Oge nzipu: Feb-23-2023