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He mea koʻikoʻi ka palena o nā hydrogels fibrous i nā capillaries liʻiliʻi i nā ʻōnaehana biological a me biomedical.Ua aʻo nui ʻia ka hoʻopaʻapaʻa a me ka uniaxial o nā hydrogels fibrous, akā ʻaʻole i ʻike ʻia kā lākou pane i ka paʻa biaxial i nā capillaries.Maʻaneʻi, hōʻike mākou i ka hoʻokolohua a me ka manaʻo ʻokoʻa ka pane ʻana o nā gel filamentous i ke koʻikoʻi ma mua o nā kaulahao maʻalahi ma muli o ka asymmetry i nā waiwai mechanical o nā filament constituent, he palupalu i ka paʻi a ʻoʻoleʻa i ka haʻalulu.Ma lalo o ka paʻa ikaika, hōʻike ka fibrous gel i ka elongation liʻiliʻi a me ka emi ʻana o ka asymptotic i ka ratio biaxial Poisson i ʻole, ka hopena i ka hoʻopili ʻana i ka gel ikaika a me ka hoʻoheheʻe ʻana o ka wai ma o ka gel.Hōʻike kēia mau hopena i ke kūʻē ʻana o ka thrombi occlusive i lysis e nā mea lapaʻau a hoʻoulu i ka hoʻomohala ʻana o ka endovascular embolization mai nā fibrous gels e hoʻōki i ke koko vascular a i ʻole ke kāohi ʻana i ke kahe koko o nā maʻi maʻi.
ʻO nā ʻupena fibrous ke kumu o ke kūkulu ʻana a me ka hana o nā ʻiʻo a me nā cell ola.ʻO Actin kahi mea nui o ka cytoskeleton1;ʻO ka fibrin kahi mea nui i ka ho'ōla ʻana i ka ʻeha a me ka hoʻokumu ʻana o ka thrombus2, a ʻo ka collagen, elastin a me fibronectin nā ʻāpana o ka matrix extracellular i ke aupuni holoholona3.Ua lilo nā ʻupena i hoʻihoʻi ʻia o nā biopolymers fibrous i mea me ka hoʻohana ākea i ka ʻenekinia kiko4.
Hōʻike ʻia nā ʻupena filamentous i kahi papa ʻokoʻa o nā mea palupalu olaola me nā ʻano mekini ʻokoʻa me nā ʻupena molekala maʻalahi5.Ua ulu aʻe kekahi o kēia mau waiwai i ke ʻano o ka hoʻomohala ʻana e hoʻomalu i ka pane ʻana o nā mea ola i ka deformation6.No ka laʻana, hōʻike nā ʻupena fibrous i ka elasticity linear ma nā kānana liʻiliʻi7,8 ʻoiai ma nā ʻano nui e hōʻike ana lākou i ka hoʻonui ʻana i ka ʻoʻoleʻa9,10, a laila e hoʻomau i ka pono o ke kino.ʻAʻole i ʻike ʻia nā hopena no nā ʻano mīkini ʻē aʻe o nā gel fibrous, e like me ke koʻikoʻi maʻamau maikaʻi ʻole i ka pane ʻana i ka shear strain11,12.
Ua aʻo ʻia nā waiwai mechanical o semi-flexible fibrous hydrogels ma lalo o ka uniaxial tension13,14 a me ka compression8,15, akā ʻaʻole i aʻo ʻia ko lākou kūʻokoʻa-induced biaxial compression i nā capillaries haiki a i ʻole nā paipu.Ma ʻaneʻi, hōʻike mākou i nā hopena hoʻokolohua a manaʻo ʻia he ʻano hana no ka hana ʻana o nā hydrogels fibrous ma lalo o ka paʻa biaxial i nā kahawai microfluidic.
ʻO nā microgels fibrin me nā ʻano like ʻole o ka fibrinogen a me ka thrombin concentrations a me kahi anawaena D0 mai 150 a 220 µm i hana ʻia me ka hoʻohana ʻana i kahi microfluidic approach (Supplementary Figure 1).Ma ka fig.Hōʻike ka 1a i nā kiʻi o nā microgels i hoʻopaʻa ʻia i ka fluorochrome i loaʻa me ka confocal fluorescence microscopy (CFM).He spherical nā microgels, he polydispersity ma lalo o 5%, a ua ʻano like ke ʻano o nā unahi i nānā ʻia e CFM (Supplementary Information and Movies S1 a me S2).ʻO ka awelika pore nui o nā microgels (i hoʻoholo ʻia ma ke ana ʻana i ka Darcy permeability16) ua emi mai ka 2280 a i ka 60 nm, ua hoʻonui ʻia ka nui o ka fibrin mai 5.25 a i 37.9 mg / mL, a ua emi ka thrombin concentration mai 2.56 a i 0.27 units / mL.(ʻIke Hou).Laiki.2), 3 a me ka papa kuhikuhi 1).Hoʻonui ka ʻoʻoleʻa like o ka microgel mai 0.85 a i 3.6 kPa (Hoʻohui Fig. 4).E like me nā hiʻohiʻona o nā gels i hoʻokumu ʻia mai nā kaulahao maʻalahi, hoʻohana ʻia nā microgels agarose o nā ʻano paʻakikī.
ʻO ke kiʻi microscopy fluorescence o fluorescein isothiocyanate (FITC) i kapa ʻia ʻo PM i hoʻokuʻu ʻia ma TBS.ʻO 500 µm ka pālākiō.b nā kiʻi SEM o SM (luna) a me RM (lalo).ʻO ka pā unahi 500 nm.c Ke kiʻikuhi kiʻi o kahi awāwa microfluidic i loko o kahi awāwa nui (diameter dl) a me kahi ʻāpana ʻano cone haiki me kahi kihi komo α o 15° a me ke anawaena o dc = 65 µm.d Mai ka hema a i ka ʻākau: Nā kiʻi microscope oki o RM (diameter D0) ma nā kaha nui, conical zone a me ka constriction (palena i ka lōʻihi gel Dz).ʻO 100 µm ka pālākiō.e, f nā kiʻi TEM o ka RM (e) a me ka RM (f) i hoʻopaʻa ʻia, i hoʻopaʻa ʻia no hoʻokahi hola me ka constriction 1/λr = 2.7, a ukali ʻia e ka hoʻokuʻu ʻana a me ka hoʻopaʻa ʻana o 5% o ka nuipa.glutaraldehyde ma TBS.ʻO ke anawaena o ka CO undeformed he 176 μm.ʻO 100 nm ka pae pālākiō.
Ua nānā mākou i nā microgels fibrin me ka paʻakikī o 0.85, 1.87 a me 3.6 kPa (ma hope i kapa ʻia ʻo nā microgels palupalu (SM), nā microgels paʻakikī (MM) a me nā microgels paʻakikī (RM).ʻO kēia ʻano o ka fibrin gel stiffness he like ia o ka nui o ka nui o ke koko 18,19 a no laila ua pili pono nā fibrin gels i aʻo ʻia i kā mākou hana i nā ʻōnaehana ola maoli.Ma ka fig.Hōʻike ka 1b i nā kiʻi o luna a me lalo o nā hale SM a me RM i loaʻa me ka scanning electron microscope (SEM), kēlā me kēia.Ke hoʻohālikelike ʻia me nā hale RM, ua hoʻokumu ʻia nā ʻupena SM e nā fiber ʻoi aku ka mānoanoa a me nā wahi lālā liʻiliʻi, e kūlike me nā hōʻike mua 20, 21 (Supplementary Fig. 5).Hoʻopili ka ʻokoʻa o ke ʻano o ka hydrogel me ke ʻano o kāna mau waiwai: ke emi nei ka permeability o ka gel me ka emi ʻana o ka nui o ka pore mai SM a MM a me RM (Paʻi Hoʻohui 1), a hoʻohuli ka ʻoʻoleʻa o ka gel.ʻAʻole i ʻike ʻia nā loli o ka microgel ma hope o ka mālama ʻana ma 4 ° C no nā lā 30 (Supplementary Fig. 6).
Ma ka fig.Hōʻike ʻo 1c i ke kiʻikuhi o kahi awāwa microfluidic me kahi ʻāpana keʻa pōʻai i loaʻa (mai ka hema a i ka ʻākau): kahi awāwa nui me ke anawaena dl kahi i noho ʻole ai ka microgel, kahi ʻāpana ʻano cone me kahi haiki i ke anawaena dc < D0, cone -ʻano ʻāpana a me nā kaha nui me ke anawaena dl (Hoʻohui Fig. 7).Ma kahi hoʻokolohua maʻamau, ua hoʻokomo ʻia nā microgels i loko o nā kahawai microfluidic ma kahi hāʻule kaomi maikaʻi ΔP o 0.2-16 kPa (Supplementary Fig. 8).Pili kēia pae puʻe i ke koko koʻikoʻi koʻikoʻi (120 mm Hg = 16 kPa)22.Ma ka fig.Hōʻike ʻo 1d (mai ka hema a i ka ʻākau) i nā kiʻi hōʻike o RM ma nā kahawai nui, nā wahi conical a me nā ʻāpana.Hoʻopaʻa ʻia ka neʻe a me ke ʻano o ka microgel me ka hoʻohana ʻana i ka polokalamu MATLAB.He mea nui e hoʻomaopopo i nā ʻāpana liʻiliʻi a me nā constrictions, aia nā microgels i ka conformal contact me nā paia o nā microchannels (Supplementary Fig. 8).ʻO ke kiʻekiʻe o ka paʻa ʻana o ka radial o ka microgel ma ka hōʻemi ʻana D0 / dc = 1 / λr aia ma ka laulā 2.4 ≤ 1 / λr ≤ 4.2, kahi 1 / λr ka lākiō kaomi.Hele ka microgel i ka emi ʻana i ka wā ΔP > ΔPtr, kahi ʻo ΔPtr ka ʻokoʻa kaomi unuhi.Hoʻoholo ʻia ka lōʻihi a me ka nui o nā pores o nā microgels biaxially constrained e ko lākou kūlana kaulike, no ka mea he mea nui e noʻonoʻo i ka viscoelasticity o nā gels i nā ʻōnaehana biological.ʻO ka manawa hoʻohālikelike no nā microgels agarose a me fibrin he 10 min a me 30 min, kēlā me kēia.Ma hope o kēia mau manawa, ua hōʻea nā microgels liʻiliʻi i ko lākou kūlana paʻa a me ke ʻano, i hopu ʻia me ke kāmela kiʻekiʻe a nānā ʻia me ka hoʻohana ʻana iā MATLAB.
Ma ka fig.1e, 1f hōʻike i nā kiʻi microscopy electron transmitted (TEM) o nā hale RM i hoʻokaʻawale ʻole ʻia a biaxially.Ma hope o ka hoʻopaʻa ʻana o RM, ua emi nui ka nui o ka microgel pore a ua lilo ko lākou ʻano i anisotropic me nā liʻiliʻi liʻiliʻi i ke kuhikuhi o ka hoʻopili ʻana, i kūlike me ka hōʻike mua 23.
ʻO ka hoʻoemi Biaxial i ka wā o ka ʻoki ʻana e hoʻolōʻihi i ka microgel i kahi ʻaoʻao palena ʻole me kahi coefficient λz = \({D}_{{{{{{{\rm{z}}}}}}}/\({D }_ { 0}\) , kahi \({D}_{{{{({\rm{z}}}}}}}}\) ka lōʻihi o ka microgel i pani ʻia. No nā microgels fibrin a me agarose He mea kupanaha, ma lalo o ke kaomi ikaika o 2.4 ≤ 1/λr ≤ 4.2, hōʻike nā microgels fibrin i ka hoʻolōʻihi ʻole ʻia o 1.12 +/- 0.03 λz, kahi i hoʻopilikia iki ʻia e ka waiwai o 1/λr. nā microgels agarose i kaupalena ʻia, i ʻike ʻia ma ka hoʻoemi nāwaliwali ʻana 1/λr = 2.6 i kahi elongation nui aʻe λz = 1.3.
a Agarose microgel hoʻokolohua me nā moduli elastic like ʻole (2.6 kPa, daimana hāmama ʻōmaʻomaʻo; 8.3 kPa, pōʻai hāmama ʻulaʻula; 12.5 kPa, ʻālani hāmama ʻalani; 20.2 kPa, huinakolu hāmama magenta) a me SM (ʻulaʻula paʻa) Hoʻololi i ke ana elongation λz ( nā pōʻai), MM (nā ʻāpana ʻeleʻele paʻa) a me RM (nā huinakolu polū paʻa).Hōʻike nā laina paʻa i ka λz i wānana mua ʻia no nā agarose (laina ʻōmaʻomaʻo) a me nā microgels fibrin (laina a me nā hōʻailona o ke kala like).b, c Panel kiʻekiʻe: kiʻi kiʻi kiʻi o nā kaulahao pūnaewele o agarose (b) a me fibrin (c) ma mua (hema) a ma hope ('ākau) biaxial compression.Ma lalo: Ke ʻano o ka pūnaewele pili ma mua a ma hope o ka hoʻololi ʻana.Hōʻike ʻia nā kuhikuhi hoʻoemi x a me y e nā pua magenta a me nā pua ʻeleʻele.Ma ke kiʻi ma luna, ua hōʻike ʻia nā kaulahao o nā ʻupena i hoʻonohonoho ʻia ma kēia mau kuhikuhi x a me y me nā laina ʻulaʻula a me nā laina ʻeleʻele e pili ana, a ʻo nā kaulahao i kuhikuhi ʻia ma kahi ʻaoʻao z i hōʻike ʻia e nā laina ʻōmaʻomaʻo.I loko o ka fibrin gel (c), ʻoi aku ka piʻo o nā laina poni a me ka ʻeleʻele ma nā ʻaoʻao x a me y ma mua o ke kūlana ʻole, a ʻo nā laina ʻōmaʻomaʻo ma ka ʻaoʻao z e piʻo a kikoo.Hoʻouna ʻia ka ʻāʻī ma waena o nā kuhikuhi o ka hoʻopaʻa ʻana a me ka neʻe ʻana ma o nā kaula me nā kuhikuhi waena.I nā gels agarose, hoʻoholo nā kaulahao ma nā ʻaoʻao a pau i ke kaomi osmotic, e hana nui ana i ka deformation o ka gel.d Manaʻo ʻia ka hoʻololi ʻana i ka lākiō Poisson biaxial, } }^{{{{\rm{eff}}}}}}}} =-{{{{{\rm{ln}}}}}}{\lambda }_{ z}/{{{{ {{ \rm{ln}}}}}}{\lambda }_{r}\ ), no ka hoʻoemi equibiaxial o nā gels agarose (laina ʻōmaʻomaʻo) a me nā fibrin (laina ʻulaʻula).Hōʻike ka inset i ka biaxial deformation o ka gel.e Hoʻololi ʻia ka hoʻololi kaomi ʻana ΔPtr, i hoʻohālikelike ʻia i ka ʻoʻoleʻa gel S, i hoʻolālā ʻia ma ke ʻano he hana o ka lākiō kōmi no nā microgels agarose a me fibrin.Pili nā kala hōʻailona me nā kala ma (a).Hōʻike nā laina ʻōmaʻomaʻo a me ka ʻulaʻula i ka pilina manaʻo ma waena o ΔPtr/S a me 1/λr no nā agarose a me nā fibrin gels.Hōʻike ka ʻāpana o ka laina ʻulaʻula i ka piʻi ʻana o ka ΔPtr ma lalo o ka paʻi ikaika ma muli o nā pilina interfiber.
Hoʻopili ʻia kēia ʻokoʻa me nā ʻano hana like ʻole o ka deformation o fibrin a me agarose microgel networks, i loaʻa i nā kaula flexible24 a me rigid25, kēlā me kēia.ʻO ka hoʻoemi Biaxial o nā gels hiki ke alakaʻi i ka emi ʻana o kā lākou leo a me ka piʻi ʻana o ka neʻe ʻana a me ka osmotic pressure, kahi e alakaʻi ai i kahi elongation o ka gel i kahi kuhikuhi palena ʻole.ʻO ka elongation hope loa o ka gel e pili ana i ke koena o ka hoʻonui ʻana i ka ikehu entropic manuahi o nā kaulahao i hoʻopaʻa ʻia a me ka emi ʻana o ka ikehu manuahi o ka osmosis ma muli o ka haʻahaʻa haʻahaʻa polymer i loko o ka gel stretched.Ma lalo o ka ikaika biaxial compression, piʻi ka elongation o ka gel me λz ≈ 0.6 \({{\lambda}_{{{\rm{r}}}}^{-2/3}}\) (e nānā i ke kiʻi 2a ma mahele kūkākūkā 5.3.3).Hōʻike ʻia nā hoʻololi conformational i nā kaulahao maʻalahi a me ke ʻano o nā pūnaewele pili ma mua a ma hope o ka paʻa biaxial.2b.
ʻOkoʻa, pane ʻokoʻa nā gel fibrous e like me fibrin i ka paʻa biaxial.ʻO nā filament i hoʻohālikelike nui ʻia me ke kuhikuhi o ka compression flex (ma laila e hōʻemi ai i ka mamao ma waena o nā loulou keʻa), ʻoiai ʻo nā filament e pili pono ana i ke kuhikuhi o ka hoʻopili ʻana a hoʻopololei ma lalo o ka hana o ka ikaika elastic, e hoʻolōʻihi i ka gel ( Fig. 1).2c) Ua hōʻike ʻia nā hale o ka SM, MM a me RM i hoʻokaʻawale ʻole ʻia e ka nānā ʻana i kā lākou mau kiʻi SEM a me CFM (Supplementary Discussion Section IV and Supplementary Figure 9).Ma ka hoʻoholo ʻana i ka modulus elastic (E), ke anawaena (d), ka lōʻihi o ka profile (R0), ka mamao ma waena o nā wēlau (L0 ≈ R0) a me ke kihi waena (ψ0) o nā kaula i loko o nā microgels fibrin undeformed (Pauna Hoʻohui 2) - 4), ʻike mākou i kēlā modulus kulou o ke kaula \({k}_{{{{{{\rm{b))))))))}=\frac{9\pi E{d}^{4} } {4 {\psi } _{0}^{2}{L}_{0}}\) he emi loa ia ma mua o kona modulus tensile\({k}_{{{{{{{\rm{s}}} } }} }}=E\frac{\pi {d}^{2}{R}_{0}}{4}\), no laila kb/ks ≈ 0.1 (Paukaukau 4).No laila, ma lalo o nā kūlana o ka paʻa ʻana o ka gel biaxial, ʻoi aku ka maʻalahi o nā kaula fibrin, akā pale i ka hoʻopololei.Hōʻike ʻia ka elongation o kahi ʻupena filamentous i hoʻopili ʻia i ka biaxial compression ma ke Kiʻi 17.
Hoʻomohala mākou i kahi kumu hoʻohālike affine (Supplementary Discussion Section V a me Supplementary Figures 10-16) kahi e hoʻoholo ʻia ai ka elongation o kahi gel fibrous mai ka equilibrium kūloko o nā ikaika elastic e hana ana i ka gel a wānana i ka ikaika biaxial strain λz - 1 malalo o ke kaohi
Hōʻike ka hoʻohālikelike (1) ʻoiai ma lalo o ke kaomi ikaika (\({\lambda }_{{{\mbox{r))))\,\to \,0\)) aia ka hoʻonui ʻana o ka gel a me ka hoʻololi ʻana o ka elongation ma hope. hoʻonaʻauao λz–1 = 0.15 ± 0.05.Pili kēia hana me (i) \({\left({k}_{{{{({\rm{b}}}}}}}}}/{k}_{{{{{{\rm { s }}}}}}}\akau)}^{1/2}\) ≈ 0.15−0.4 a me (ii) ka hua'ōlelo i loko o nā pākuʻi huinahā like asymptotically asymptotically \(1{{\mbox{/}}} \sqrt { 3 }\) no nā mea paʻa biaxial ikaika. He mea nui e hoʻomaopopo i ka prefactor \({\left({k}_{({\mbox{b))))/{k}_{({\mbox{ s))))\akau)}^{1/ 2 }\) aole pili i ka oolea o ka milo E, aka, ua hooholoia e ka ratio hiohiona o ka milo d/L0 a me ka huina waena o ke arc. ψ0, ua like ia me SM, MM a me RM (Pau 4).
No ka hōʻike hou ʻana i ka ʻokoʻa o ke koʻikoʻi i hoʻokomo ʻia i ke kūʻokoʻa ma waena o nā gels hikiwawe a me ka filamentous, hoʻolauna mākou i ka ratio biaxial Poisson \({\nu }_{{{({\rm{b)))))) }{{\ mbox { =}}}\,\mathop{{\lim}}\limits_{{\lambda}_{{{{({\rm{r}}}}}}}}\to 1}\ frac{{\ lambda } _{ {{{{\rm{z}}}}}}}-1}{1-{\lambda }_{{({\rm{r}}}}}}}}}, \) wehewehe i kahi palena ʻole ka hoʻonohonoho ʻana o ke kāʻei gel i ka pane ʻana i ke kānana like ma nā ʻaoʻao radial ʻelua, a hoʻonui i kēia i nā ʻano like ʻole nui \ rm{b }}}}}}}}}^{{{{{\rm{eff}}}}}}} }}=-{{{{{\rm{ln}}}}}}}} }{ \lambda } _{z} /{{{({\rm{ln)))))))}{\lambda }_{{{({\rm{r)))))))))}\) .Ma ka fig.2d hōʻike \({{{{{\rm{\nu }}}}}}}}}_{{{({\rm{b}}}}}}}}^{{{ {{\rm { eff }}}}}}}\) no ka hoʻopili ʻana i ka biaxial like ʻole o nā gels maʻalahi (e like me agarose) a me nā gels (e like me fibrin) (Kūkākūkā hoʻohui, Māhele 5.3.4), a hōʻike i ka pilina ma waena o nā ʻokoʻa ikaika i nā pane i ka hoʻopaʻa ʻia. No nā gel agarose ma lalo o nā kapu ikaika {\rm{eff}}}}}}}}\) piʻi aʻe i ka waiwai asymptotic 2/3, a no nā gel fibrin ua emi ia i ka ʻole, no ka mea, lnλz/lnλr → 0, no ka mea, piʻi ka λz me ka hoʻopololei i ka piʻi ʻana o λr.E hoʻomaopopo i ka hoʻokolohua ʻana, ʻoi aku ka ikaika o nā microgels spherical i hoʻopaʻa ʻia, a ʻoi aku ka ikaika o ko lākou ʻāpana waena;akā naʻe, hiki i ka extrapolation i kahi waiwai nui o 1/λr ke hoʻohālikelike i ka hoʻokolohua me ka manaʻo no nā gels deformed uniformly.
Ua ʻike ʻia kekahi ʻokoʻa ʻē aʻe i ka ʻano o nā gel kaulahao maʻalahi a me nā gel filamentous ma muli o ko lākou neʻe ʻana i ka wā ʻoki.ʻO ke kaomi translocation ΔPtr, maʻamau i ka gel stiffness S, ua hoʻonui ʻia me ka hoʻonui ʻana i ka hoʻopiʻi (Fig. 2e), akā ma 2.0 ≤ 1/λr ≤ 3.5, ua hōʻike nā fibrin microgels i nā waiwai haʻahaʻa o ΔPtr/S i lalo i ka wā shrinkage.ʻO ka paʻa ʻana o ka microgel agarose e alakaʻi i ka piʻi ʻana o ka osmotic pressure, e alakaʻi ana i ka hohola ʻana o ka gel ma ka ʻaoʻao longitudinal i ka wā e hoʻolōʻihi ʻia ai nā molekala polymer (Fig. 2b, hema) a me ka piʻi ʻana o ke kaomi translocation e ΔPtr/S ~(( 1/λr)14/317.ʻO ka mea ʻē aʻe, ua hoʻoholo ʻia ke ʻano o nā microgels fibrin i pani ʻia e ke koena o ka ikehu o nā kaula o ka radial compression a me ka longitudinal tension, e alakaʻi ana i ka deformation longitudinal kiʻekiʻe λz ~\(\sqrt{{k}_{{{ {{ { \rm{ b)))))))} /{k}_{{{{{{{\rm{s}}}}}}}}}}\).No 1/λr ≫ 1, ua hoʻonui ʻia ka hoʻololi ʻana i ke kaomi unuhi ma ke ʻano he 1 }{{{({\rm{ln))))))\left({{\lambda }}_{{{{{\rm {r} }}}}}}}^{{-} 1} \akau)\) (Kūkākūkā Pākuʻi, Māhele 5.4), e like me ka hōʻike ʻia e ka laina ʻulaʻula paʻa ma ke kiʻi 2e.No laila, ʻoi aku ka liʻiliʻi o ka ΔPtr ma mua o nā gel agarose.No ka compressions me 1/λr > 3.5, he piʻi nui i ka hapa leo o nā filament a me ka launa pū ʻana o nā filament pili e kaupalena hou i ka deformation o ka gel a alakaʻi i nā deviations o nā hopena hoʻokolohua mai nā wanana (laina ʻulaʻula kiko ma Fig. 2e).Hoʻoholo mākou no ka like 1/λr a me Δ\({P}_{{{{{{{\rm{tr}}}}}}}}}_{{{{\rm{fibrin}}} )) } }}}\) < ΔP < Δ\({P}_{{{{{{{\rm{tr))))))}}}}_{{{{\rm{agarose}} }} } } } }}\) e hopu ʻia ka gel agarose e ka microchannel, a ʻo ka fibrin gel me ka ʻoʻoleʻa like e hele ma ia.No ka ΔP < Δ\({P}_{{{{{{\rm{tr)))))))))_{{{{{\rm{fibrin))))))))}\ ), ʻElua mau gel ʻelua e ālai i ke kahawai, akā ʻoi aku ka hohonu o ka fibrin gel a hoʻopaʻa ʻoi aku ka maikaʻi, ke kāohi ʻana i ka kahe wai.Hōʻike nā hopena i hōʻike ʻia ma ke Kiʻi 2 e hiki i ka fibrous gel ke lilo i puʻupuʻu maikaʻi e hōʻemi i ke koko a i ʻole ke kāohi ʻana i ke kahe koko i nā ʻōpū.
Ma kekahiʻaoʻao, hana ka fibrin i kahi scaffold clot e alakaʻi ai i ka thromboembolism, kahi maʻi pathological kahi e hoʻopaʻa ai kahi thrombus i kahi moku ma ΔP < ΔPtr, e like me kekahi mauʻano o ka maʻi ischemic (Fig. 3a).ʻO ka hoʻonui ʻia ʻana o ka fibrin microgels i ʻoi aku ka ikaika o ka hoʻonui ʻana o ka fibrin o ka C / C fibrinogen i hoʻohālikelike ʻia me nā kaulahao maʻalahi, kahi i kaupalena ʻia ai ʻo C a me C fibrinogen a me nā microgels ʻole.ʻO ka hoʻopaʻa ʻana o ka polymer i ka gel.Hōʻike ke kiʻi 3b i ka fibrinogen C / C ma SM, MM, a me RM i piʻi aʻe ma mua o ʻehiku mau paʻi ma 1 / λr ≈ 4.0, i alakaʻi ʻia e ka palena a me ka dehydration (Supplementary Fig. 16).
Hōʻike hoʻohālike o ka occlusion o ke aʻa cerebral waena i loko o ka lolo.b Hoʻonui pili pili i ka hoʻopaʻa ʻia ʻana o ka fibrin i loko o SM obstructive SM (nā pōʻai ʻulaʻula paʻa), MM (nā ʻāpana ʻeleʻele paʻa), a me RM (nā huinakolu polū paʻa).c Hoʻolālā hoʻokolohua i hoʻohana ʻia e aʻo i ka ʻoki ʻana o nā gel fibrin i kaupalena ʻia.Ua hoʻokomo ʻia kahi hopena o ka tPA i kapa ʻia i ka fluorescently i TBS ma kahi kahe kahe o 5.6 × 107 µm3/s a me kahi hāʻule kaomi hou o 0.7 Pa no nā kahawai e kū pololei ana i ke axis lōʻihi o ka microchannel nui.d Hoʻohui ʻia ke kiʻi microscopic multichannel o keakea MM (D0 = 200 µm) ma Xf = 28 µm, ΔP = 700 Pa a i ka wā e māhele ai.Hōʻike nā laina kiko pololei i nā kūlana mua o nā ʻaoʻao hope a me mua o ka MM ma tlys = 0. ʻO nā waihoʻoluʻu ʻōmaʻomaʻo a me ka ʻulaʻula e pili ana me FITC-dextran (70 kDa) a me ka tPA i kapa ʻia me AlexaFluor633.e Hoʻololi manawa like ʻole ka nui o nā RMs i hoʻopaʻa ʻia me D0 o 174 µm ( huinakolu hāmama ʻulaʻula), 199 µm ( huinakolu hāmama uliuli), a me 218 µm ( huinakolu hāmama ʻulaʻula ), i kēlā me kēia, i loko o kahi microchannel conical me Xf = 28 ± 1 µm.na pauku he ΔP 1200, 1800, a me 3000 Pa, a me Q = 1860 ± 70 µm3/s.Hōʻike ka mea hoʻokomo iā RM (D0 = 218 µm) e hoʻopili ana i ka microchannel.f Hoʻololi manawa o ka leo pili o SM, MM a i ʻole RM i kau ʻia ma Xf = 32 ± 12 µm, ma ΔP 400, 750 a me 1800 Pa a me ΔP 12300 Pa a me Q 12300 ma ka ʻāpana conical o ka microchannel, kēlā me kēia 2400 a me 18360 µm. /s.Hōʻike ʻo Xf i ke kūlana mua o ka microgel a hoʻoholo i kona mamao mai ka hoʻomaka ʻana o ka shrinkage.ʻO V(tlys) a me V0 ka leo pōkole o ka microgel lysed a me ka leo o ka microgel undisturbed, kēlā me kēia.Kūlike nā kala ʻano me nā kala ma b.ʻO nā pua ʻeleʻele ma e, f pili i ka manawa hope ma mua o ka hele ʻana o nā microgels ma o ka microchannel.ʻO ka pā unahi ma d, e he 100 µm.
No ka noiʻi ʻana i ka hopena o ke kaohi ʻana i ka hoʻemi ʻana o ka wai ma waena o nā gels fibrin obstructive, ua aʻo mākou i ka lysis o SM, MM, a me RM infiltrated me ka thrombolytic agent tissue plasminogen activator (tPA).Hōʻike ka 3c i ka hoʻolālā hoʻokolohua i hoʻohana ʻia no nā hoʻokolohua lysis. Ma ΔP = 700 Pa (<ΔPtr) a me kahi kahe kahe, Q = 2400 μm3/s, o Tris-buffered saline (TBS) i hui pū ʻia me 0.1 mg/mL o (fluorescein isothiocyanate) FITC-Dextran, ua hoʻopaʻa ka microgel i ka microchannel tapered māhele ʻāina. Ma ΔP = 700 Pa (<ΔPtr) a me kahi kahe kahe, Q = 2400 μm3/s, o Tris-buffered saline (TBS) i hui pū ʻia me 0.1 mg/mL o (fluorescein isothiocyanate) FITC-Dextran, ua hoʻopaʻa ka microgel i ka microchannel tapered māhele ʻāina. При ΔP = 700 Па (<ΔPtr) a me скорости потока, Q = 2400 мкм3/с, трис-буферного солевого раствора (TBS), смешангного мсуфорный цианата) FITC-декстрана, микрогель перекрывал сужающийся микроканал. Ma ΔP = 700 Pa (<ΔPtr) a me kahi kahe kahe, Q = 2400 µm3/s, o Tris buffered saline (TBS) i hui pū ʻia me 0.1 mg/mL (fluorescein isothiocyanate) FITC-dextran, ua hoʻopaʻa ka microgel i ka microchannel converging.māhele ʻāina.在ΔP = 700 Pa (<ΔPtr) 和流速Q = 2400 µm3/s时，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 (флуоресцеинизотио 0,1 мг/мл (флуоресцеинизотио) FITC-пинизотио а (<ΔPtr) и скорости потока Q = 2400 мкм3/с Конические области микроканалов. Hoʻopili ʻia nā Microgels i ka wā i hui ʻia ai ʻo Tris buffered saline (TBS) me 0.1mg/mL (fluorescein isothiocyanate) FITC-dextran ma ΔP = 700 Pa (<ΔPtr) a me ke kahe kahe Q = 2400 µm3/s Conical māhele o microchannels.ʻO ke kūlana mua Xf o ka microgel e hoʻoholo ai i kona mamao mai ka helu hoʻomaka mua X0.No ka hoʻoulu ʻana i ka lysis, ua hoʻoheheʻe ʻia kahi hopena o ka tPA i kapa ʻia i ka fluorescently i TBS mai kahi awāwa i loaʻa i ka orthogonally a i ke axis lōʻihi o ka microchannel nui.
I ka hiki ʻana o ka hopena tPA i ka MM occlusal, ua pōwehiwehi ka ʻaoʻao hope o ka microgel, e hōʻike ana ua hoʻomaka ka cleavage fibrin i ka manawa tlys = 0 (Fig. 3d and Supplementary Fig. 18).I ka wā o ka fibrinolysis, hōʻiliʻili ka tPA i kapa ʻia i ka wai i loko o ka MM a hoʻopaʻa i nā kaula fibrin, e alakaʻi ana i ka hoʻonui mālie i ka ikaika o ka waihoʻoluʻu ʻulaʻula o nā microgels.Ma tlys = 60 min, ʻaelike ka MM ma muli o ka hemo ʻana o kona ʻaoʻao hope, a hoʻololi iki ke kūlana o kona ʻaoʻao alakaʻi Xf.Ma hope o 160 min, ua hoʻomau ka MM i hoʻopaʻa ikaika ʻia i ka ʻaelike, a ma ka tlys = 161 min, ua hoʻihoʻi ʻia ka kahe wai ma o ka microchannel (Fig. 3d and Supplementary Fig. 18, kolamu ʻākau).
Ma ka fig.Hōʻike ka 3e i ka emi ʻana o ka manawa i hoʻopaʻa ʻia i ka lysis i ka leo V(tlys) i maʻamau i ka leo mua V0 o nā microgels fibrin like ʻole.Hoʻokomo ʻia ʻo CO me D0 174, 199, a i ʻole 218 µm i loko o kahi microchannel me ΔP 1200, 1800, a i ʻole 3000 Pa, kēlā me kēia, a me Q = 1860 ± 70 µm3/s e ālai i ka microchannel (Fig. 3e, inset).meaʻai.Hoʻemi mālie nā microgels a hiki i ka liʻiliʻi e hele i nā kahawai.ʻO ka emi ʻana o ka nui koʻikoʻi o CO me kahi anawaena mua nui aʻe e pono ai ka manawa lysis lōʻihi.Ma muli o ke kahe like ʻana ma waena o nā RMs nui like ʻole, hiki ke ʻoki ʻia ma ka helu like, ka hopena o ka hoʻoemi ʻana i nā ʻāpana liʻiliʻi o nā RM nui a me kā lākou unuhi lohi.Ma ka fig.Hōʻike ka 3f i ka hoʻemi pili ʻana ma V(tlys)/V0 ma muli o ka māhele ʻana no SM, MM, a me RM ma D0 = 197 ± 3 µm i hoʻolālā ʻia ma ke ʻano he hana o nā tlys.No SM, MM a me RM, e kau i kēlā me kēia microgel i loko o kahi microchannel me ΔP 400, 750 a i ʻole 1800 Pa a me Q 12300, 2400 a i ʻole 1860 µm3/s.ʻOiai ʻo ke kaomi i hoʻohana ʻia i ka SM he 4.5 mau manawa haʻahaʻa ma mua o ka RM, ʻoi aku ka nui o ka kahe ma ka SM ma mua o ʻeono mau manawa ikaika ma muli o ke kiʻekiʻe kiʻekiʻe o ka SM, a ua emi ka emi ʻana o ka microgel mai SM a MM a me RM. .No ka laʻana, ma tlys = 78 min, ʻo SM ka hapa nui i hoʻoheheʻe ʻia a hoʻoneʻe ʻia, ʻoiai ʻo MM a me PM e hoʻomau i ka hoʻopaʻa ʻana i nā microchannels, ʻoiai ke mālama ʻia nei he 16% a me 20% o kā lākou leo kumu, kēlā me kēia.Hōʻike kēia mau hualoaʻa i ke koʻikoʻi o ka convection-mediated lysis o constricted fibrous gels a hoʻopili ʻia me nā hōʻike o ka wikiwiki ʻana o nā clots me ka haʻahaʻa o ka fibrin.
No laila, hōʻike kā mākou hana i ka hoʻokolohua a me ka manaʻo i ke ʻano e pane ai nā gel filamentous i ka paʻa biaxial.Hoʻoholo ʻia ke ʻano o nā gels fibrous i kahi ākea e ka asymmetry ikaika o ka ikaika o nā filament (malū i ka hoʻoemi a paʻakikī i ka hoʻopaʻapaʻa) a ma ka ʻaoʻao wale nō a me ka curvature o nā filament.ʻO kēia hopena ka hopena i ka liʻiliʻi o ka hoʻolōʻihi ʻia o nā gel fibrous i loko o nā capillaries haiki, ke emi nei ko lākou biaxial Poisson's ratio me ka hoʻonui ʻana i ka hoʻopiʻi a me ka liʻiliʻi o ka puʻe māmā.
No ka hoʻohana ʻana o ka biaxial i nā ʻāpana palupalu palupalu i nā ʻenehana ākea, hoʻoulu kā mākou hopena i ka hoʻomohala ʻana i nā mea fibrous hou.ʻO ka mea kūikawā, ʻo ka paʻa biaxial o nā gel filamentous i nā capillaries liʻiliʻi a i ʻole nā paipu e alakaʻi ai i kā lākou compaction ikaika a me ka emi ʻana o ka permeability.Loaʻa ka maikaʻi o ka pale ʻana i ka kahe o ka wai ma o ka occlusive fibrous gels ke hoʻohana ʻia e like me nā plugs e pale ai i ke koko a i ʻole e hōʻemi i ka hāʻawi ʻana i ke koko i nā malignancies33,34,35.Ma ka ʻaoʻao ʻē aʻe, ʻo ka emi ʻana o ka kahe o ka wai ma o ka occlusal fibrin gel, no laila ke kāohi nei i ka convective-mediated thrombus lysis, e hōʻike ana i ka lysis lohi o nā clots occlusal [27, 36, 37].ʻO kā mākou ʻōnaehana hoʻohālike ka hana mua i ka hoʻomaopopo ʻana i nā hopena o ka pane mechanical o nā fibrous biopolymer hydrogels i ka paʻa biaxial.ʻO ka hoʻokomo ʻana i nā ʻāpana koko a i ʻole platelets i loko o nā gel fibrin obstructive e hoʻopilikia i kā lākou ʻano kaohi 38 a ʻo ia ka hana hou e wehe ai i ka ʻano o nā ʻōnaehana koʻikoʻi koʻikoʻi.
Hōʻike ʻia nā reagents e hoʻomākaukau ai i nā microgels fibrin a me ka hana ʻana i nā mea hana MF ma ka ʻike ʻikepili hou (Pauku 2 a me 4).Ua hoʻomākaukau ʻia nā microgels fibrin ma ka hoʻoheheʻe ʻana i kahi hopena hui ʻia o fibrinogen, Tris buffer a me thrombin i loko o kahi hāmeʻa MF e nānā pono ana, a ukali ʻia e ka droplet gelation.ʻO ka bovine fibrinogen solution (60 mg/ml ma TBS), Tris buffer a me bovine thrombin solution (5 U/ml i ka 10 mM CaCl2 solution) ua lawelawe ʻia me ka hoʻohana ʻana i ʻelua mau pamu syringe i hoʻokele kūʻokoʻa ʻia (PhD 200 Harvard Apparatus PHD 2000 Syring Pump).e ālai iā MF, USA).ʻO ka ʻaila F-ʻaila hoʻomau i loaʻa ka 1 wt.% block copolymer PFPE-P(EO-PO)-PFPE, ua hoʻokomo ʻia i loko o ka pūʻulu MF me ka hoʻohana ʻana i ke kolu o ka pamu syringe.ʻO nā droplets i hana ʻia i loko o ka mea MF e hōʻiliʻili ʻia i loko o kahi pahu centrifuge 15 ml me ka aila F.E kau i nā paipu i loko o ka ʻauʻau wai ma 37 °C no 1 hola e hoʻopau ai i ka fibrin gelation.Ua hoʻomākaukau ʻia nā microgels fibrin i kapa ʻia ʻo FITC ma ka hui ʻana i ka fibrinogen bovine a me ka FITC i kapa ʻia ʻo fibrinogen kanaka i ka ratio paona 33:1.ʻO ke kaʻina hana e like me ka hoʻomākaukau ʻana i nā microgels fibrin.
E hoʻololi i nā microgels mai ka aila F a i ka TBS ma ka centrifuging i ka dispersion ma 185 g no 2 min.Hoʻopuehu ʻia nā microgels precipitated i ka aila F i hui pū ʻia me 20 wt.% perfluorooctyl alcohol, a laila hoʻopuehu ʻia i loko o ka hexane i loaʻa ka 0.5 wt.% Span 80, hexane, 0.1 wt.% Triton X i ka wai a me TBS.ʻO ka hope, ua hoʻopuehu ʻia nā microgels i loko o ka TBS i loaʻa ka 0.01 wt% Ma waena o 20 a mālama ʻia ma 4 ° C no kahi o 1-2 mau pule ma mua o nā hoʻokolohua.
Hōʻike ʻia ka hana ʻana o ka hāmeʻa MF ma ka ʻIke Hoʻohui (Pūnaehana Pākuʻi 5).Ma kahi hoʻokolohua maʻamau, hoʻoholo ʻia ka waiwai maikaʻi o ΔP e ke kiʻekiʻe pili o nā loko i hoʻopili ʻia ma mua a ma hope o ka hāmeʻa MF no ka hoʻokomo ʻana i nā microgels me ke anawaena o 150 < D0 < 270 µm i loko o nā microchannels.Ua hoʻoholo ʻia ka nui o nā microgels ma ka nānā ʻana iā lākou ma ka macrochannel.Kū ka microgel ma kahi conical ma ka puka o ka constriction.Ke hoʻololi ʻole ka piko o ka microgel mua no 2 min, e hoʻohana i ka polokalamu MATLAB e hoʻoholo i ke kūlana o ka microgel ma ka x-axis.Me ka piʻi ʻana o ka stepwise i ka ΔP, neʻe ka microgel ma ke ʻano o ka wedge a hiki i ke komo ʻana i ka constriction.Ke hoʻokomo piha ʻia ka microgel a hoʻopaʻa ʻia, hāʻule koke ka ΔP i ka ʻole, ke kaulike ʻana i ka pae wai ma waena o nā waihona, a paʻa ka microgel i pani ʻia ma lalo o ke kaomi.Ua ana ʻia ka lōʻihi o ka microgel obstructive 30 min ma hope o ka pau ʻana o ka constriction.
I ka wā o nā hoʻokolohua fibrinolysis, ua komo nā hāʻina o ka t-PA a me ka FITC-labeled dextran i nā microgels i pāpā ʻia.Ua nānā ʻia ke kahe o kēlā me kēia wai me ka hoʻohana ʻana i ke kiʻi fluorescence hoʻokahi.Hoʻopili ʻia ʻo TAP me ka AlexaFluor 633 i hoʻopili ʻia i nā fibrin fibers a hōʻiliʻili ʻia i loko o nā microgels fibrin compressed (Kili TRITC ma ke Kiʻi 18).ʻO ka hopena dextran i hōʻailona ʻia me ka FITC e neʻe me ka ʻole o ka hōʻiliʻili ʻana i ka microgel.
Loaʻa nā ʻikepili e kākoʻo ana i nā hopena o kēia noiʻi mai nā mea kākau paʻa ma ke noi.ʻO nā kiʻi SEM Raw o nā fibrin gels, nā kiʻi TEM raw o nā fibrin gels ma mua a ma hope o ka inoculation, a me nāʻikepili komo nui no nā Kiʻi 1 a me 2. 2 a me 3 i hoʻolakoʻia i ka waihonaʻike maka.Hāʻawi kēia ʻatikala i ka ʻikepili kumu.
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