Na gode da ziyartar Nature.com.Kuna amfani da sigar burauza tare da iyakancewar tallafin CSS.Don ƙwarewa mafi kyau, muna ba da shawarar ku yi amfani da sabuntar burauza (ko kuma musaki Yanayin dacewa a cikin Internet Explorer).Bugu da ƙari, don tabbatar da goyon baya mai gudana, muna nuna shafin ba tare da salo da JavaScript ba.
Yana nuna carousel na nunin faifai uku lokaci guda.Yi amfani da maɓallan da suka gabata da na gaba don matsawa ta cikin nunin faifai guda uku a lokaci ɗaya, ko amfani da maɓallan maɓalli a ƙarshen don matsawa ta cikin nunin faifai uku a lokaci ɗaya.
Iyakance fibrous hydrogels zuwa kunkuntar capillaries yana da matukar mahimmanci a cikin tsarin ilimin halitta da na halitta.An yi nazari da yawa game da tashin hankali da matsawa uniaxial na fibrous hydrogels, amma amsawar su ga riƙewar biaxial a cikin capillaries ya kasance ba a gano su ba.Anan, muna nuna gwaji da ka'idar cewa gels na filamentous suna amsawa da inganci daban-daban don ƙuntatawa fiye da gels masu sassaucin ra'ayi saboda asymmetry a cikin kayan aikin injiniya na filaye masu ƙima, waɗanda ke da taushi a cikin matsawa da ƙarfi cikin tashin hankali.Ƙarƙashin riƙewa mai ƙarfi, gel ɗin fibrous yana nuna ɗan ƙara haɓakawa da raguwar asymptotic a cikin rabon biaxial Poisson zuwa sifili, yana haifar da haɓakar gel mai ƙarfi da ƙarancin shigar ruwa ta gel.Wadannan sakamakon suna nuna juriya na ƙwanƙwasa occlusive thrombi zuwa lysis ta hanyar magungunan warkewa kuma suna ƙarfafa haɓakar haɓakar haɓakar endovascular mai tasiri daga gels fibrous don dakatar da zubar jini na jijiyoyin jini ko hana samar da jini na ciwace-ciwace.
Cibiyoyin Fibrous su ne ainihin ginshiƙan ginshiƙan ginshiƙan kyallen takarda da sel masu rai.Actin shine babban sashi na cytoskeleton1;Fibrin wani mahimmin sinadari ne a cikin warkar da rauni da samuwar thrombus2, kuma collagen, elastin da fibronectin su ne sassan matrix na extracellular a cikin daular dabba3.Cibiyoyin da aka dawo da su na fibrous biopolymers sun zama kayan aiki tare da aikace-aikace masu yawa a cikin injiniyan nama4.
Cibiyoyin hanyoyin sadarwa suna wakiltar wani nau'i daban-daban na kwayoyin halitta mai laushi tare da kaddarorin inji waɗanda suka bambanta da hanyoyin sadarwa masu sassauƙa.Wasu daga cikin waɗannan kaddarorin sun samo asali a cikin tsarin juyin halitta don sarrafa martanin kwayoyin halitta zuwa nakasu6.Misali, cibiyoyin sadarwa na fibrous suna nuna elasticity na layi a ƙananan nau'ikan nau'ikan7,8 yayin da a manyan nau'ikan suna nuna ƙara ƙarfi9,10, don haka suna riƙe amincin nama.Abubuwan da ke haifar da wasu kaddarorin inji na gels fibrous, irin su mummunan damuwa na al'ada don mayar da martani ga nau'in shear11,12, har yanzu ba a gano su ba.
An yi nazarin kaddarorin injiniyoyi masu sassaucin ra'ayi na fibrous hydrogels a ƙarƙashin uniaxial tension13,14 da compression8,15, amma ba a yi nazarin ƴancin su da ke haifar da matsawa biaxial a cikin kunkuntar capillaries ko tubes ba.Anan muna ba da rahoton sakamakon gwaji kuma a ka'ida muna ba da shawarar wata hanya don halayen fibrous hydrogels ƙarƙashin riƙewar biaxial a cikin tashoshi na microfluidic.
Fibrin microgels tare da nau'o'i daban-daban na fibrinogen da ƙananan thrombin da diamita na D0 daga 150 zuwa 220 µm an samo su ta amfani da tsarin microfluidic (Ƙarin Hoto 1).A kan fig.1a yana nuna hotuna na microgels masu alamar fluorochrome da aka samu ta amfani da microscopy confocal fluorescence microscopy (CFM).Microgels suna da siffar zobe, suna da rarrabuwar ƙasa da ƙasa da 5%, kuma sun kasance iri ɗaya cikin tsari a cikin ma'auni da CFM (Ƙarin Bayani da Fina-finai S1 da S2 ke dubawa).Matsakaicin girman pore na microgels (an ƙaddara ta hanyar aunawa Darcy permeability16) ya ragu daga 2280 zuwa 60 nm, abun ciki na fibrin ya karu daga 5.25 zuwa 37.9 mg / ml, kuma ƙwayar thrombin ya ragu daga 2.56 zuwa 0.27 raka'a / mL, bi da bi.(Ƙarin Bayani).Shinkafa2), 3 da ƙarin tebur 1).Matsakaicin madaidaicin microgel yana ƙaruwa daga 0.85 zuwa 3.6 kPa (Ƙarin Hoton 4).A matsayin misalan gels da aka samo daga sarƙoƙi masu sassauƙa, ana amfani da microgels agarose na taurin kai.
Hoton microscope na Fluorescence na fluorescein isothiocyanate (FITC) mai lakabin PM an dakatar da shi a cikin TBS.Ma'auni na mashaya shine 500 µm.b Hotunan SEM na SM (saman) da RM (kasa).Matsakaicin girman 500 nm.c Tsarin tsari na tashar microfluidic mai kunshe da babban tasho (diamita dl) da yanki mai siffar mazugi mai kunkuntar tare da kusurwar shigarwa α na 15° da diamita na dc = 65 µm.d Hagu zuwa dama: Hotunan microscope na gani na RM (diamita D0) a cikin manyan tashoshi, yanki mai juzu'i da ƙuntatawa (ƙayyade tsawon gel Dz).Ma'auni na mashaya shine 100 µm.e, f Hotunan TEM na RM mara kyau (e) da RM (f) maras kyau, gyarawa na sa'a daya tare da ƙuntatawa 1 / λr = 2.7, sannan saki da gyarawa na 5% na taro.glutaraldehyde a cikin TBS.Diamita na CO mara kyau shine 176 μm.Matsakaicin sikelin shine 100 nm.
Mun mayar da hankali kan microgels na fibrin tare da taurin 0.85, 1.87 da 3.6 kPa (nan gaba ana magana da su azaman microgels masu laushi (SM), matsakaicin wuyan microgels (MM) da ƙananan microgels (RM), bi da bi).Wannan kewayon fibrin gel stiffness yana da tsari iri ɗaya kamar na ɗigon jini18,19 don haka fibrin gels da aka yi nazari a cikin aikinmu suna da alaƙa kai tsaye da tsarin halittu na ainihi.A kan fig.1b yana nuna hotuna na sama da kasa na tsarin SM da RM da aka samu ta amfani da microscope na lantarki (SEM), bi da bi.Idan aka kwatanta da tsarin RM, hanyoyin sadarwar SM suna samuwa ta hanyar filaye masu kauri da ƙananan maki reshe, daidai da rahotannin da suka gabata 20, 21 (Ƙarin Hoton 5).Bambance-bambance a cikin tsarin hydrogel ya dace da yanayin halayensa: ƙarancin gel ɗin yana raguwa tare da rage girman pore daga SM zuwa MM da RM (Ƙarin Teburin 1), kuma taurin gel ɗin yana juyawa.Ba a lura da canje-canje a cikin tsarin microgel ba bayan ajiya a 4 ° C na kwanaki 30 (Ƙarin Hoton 6).
A kan fig.1c yana nuna zane na tashar microfluidic tare da sashin giciye na madauwari wanda ya ƙunshi (daga hagu zuwa dama): babban tashar da diamita dl wanda microgel ya kasance maras kyau, wani sashi mai siffar mazugi tare da raguwa a diamita dc
A kan fig.1e.Bayan matsawa na RM, girman pore microgel ya ragu sosai kuma siffar su ta zama anisotropic tare da ƙananan girma a cikin jagorancin matsawa, wanda ya dace da rahoton da ya gabata 23.
Matsi na biaxial a lokacin ƙanƙara yana haifar da microgel don yin tsawo a cikin hanya mara iyaka tare da ƙididdiga λz = ({D}_{{{{{{{\rm{z}}}}}}}}}/\({D }_ {{{{{{\rm{z}}}}}}}}}) 0}\), inda \({D}_{{{{({\rm{z}}}}}}}})) shine tsayin rufaffiyar microgel Hoto 2a yana nuna canji a λzvs .1/ λr Don fibrin da agarose microgels. Ƙayyadaddun microgels na agarose, waɗanda aka lura har ma a matsawa mai rauni 1 / λr = 2.6 zuwa mafi girma elongation λz = 1.3.
a Agarose microgel gwaje-gwaje tare da daban-daban na roba moduli (2.6 kPa, kore bude lu'u-lu'u; 8.3 kPa, launin ruwan kasa bude da'irar; 12.5 kPa, orange bude square; 20.2 kPa, magenta bude inverted alwatika) da SM (m ja) Canja a auna elongation λz ( da'irori), MM (m baƙar fata murabba'ai) da RM (m blue triangles).Layuka masu ƙarfi suna nuna λz da aka annabta na agrose (layin kore) da fibrin microgels (layi da alamomin launi ɗaya).b, c Babban panel: zane-zane na sarƙoƙin cibiyar sadarwa na agarose (b) da fibrin (c) kafin (hagu) da bayan (dama) matsawar biaxial.Kasa: Siffar hanyar sadarwar da ta dace kafin da bayan nakasawa.Ana nuna kwatancen matsi na x da y ta magenta da kiban launin ruwan kasa, bi da bi.A cikin hoton da ke sama, ana nuna sarƙoƙin cibiyoyin sadarwa waɗanda ke cikin waɗannan kwatance x da y tare da magenta da layukan launin ruwan kasa daidai, kuma sarƙoƙin da ke kan hanyar z na sabani ana wakilta su da koren layi.A cikin fibrin gel (c), layukan shunayya da launin ruwan kasa a cikin kwatancen x da y suna lanƙwasa fiye da yanayin da ba su da lahani, kuma korayen da ke cikin hanyar z suna lanƙwasa da shimfiɗawa.Ana watsa tashin hankali tsakanin kwatance na matsawa da tashin hankali ta hanyar zaren tare da matsakaicin kwatance.A cikin gels na agarose, sarƙoƙi a duk kwatance suna ƙayyade matsa lamba na osmotic, wanda ke ba da gudummawa mai mahimmanci ga lalata gel.d Canjin da aka annabta a cikin rabon biaxial Poisson, }} ^{{{{\rm{eff}}}}}} =-{{{{{{{\rm{ln}}}}}}}}{\lambda }_{ z}/{{{{{\rm{ln}}}}}}}, don daidaita ma'aunin agarose (layin kore) da fibrin (layin jan) gels.A ciki yana nuna nakasar biaxial na gel.e Canjin matsa lamba ΔPtr, wanda aka daidaita zuwa gel stiffness S, an tsara shi azaman aikin matsi don agarose da fibrin microgels.Launukan alamar sun dace da launuka a cikin (a).Layukan kore da ja suna nuna alaƙar ka'idar tsakanin ΔPtr/S da 1/λr don gels na agarose da fibrin, bi da bi.Sashin da aka soke na layin ja yana nuna haɓakar ΔPtr a ƙarƙashin matsawa mai ƙarfi saboda hulɗar interfiber.
Wannan bambance-bambance yana da alaƙa da hanyoyi daban-daban na nakasar fibrin da cibiyoyin sadarwa na agarose microgel, waɗanda suka ƙunshi sassauƙa24 da zaren rigid25, bi da bi.Matsi na biaxial na gels masu sassaucin ra'ayi yana haifar da raguwa a cikin ƙarar su da haɓakar haɓakawa a cikin maida hankali da matsa lamba na osmotic, wanda ke haifar da haɓakar gel a cikin hanya marar iyaka.Ƙarshe na ƙarshe na gel ɗin ya dogara da ma'auni na karuwa a cikin makamashi na kyauta na entropic na sassan da aka shimfiɗa da kuma raguwa a cikin makamashi na kyauta na osmosis saboda ƙananan ƙwayar polymer a cikin gel mai shimfiɗa.Ƙarƙashin matsawa mai ƙarfi na biaxial, haɓakar gel ɗin yana ƙaruwa tare da λz ≈ 0.6 \({{\lambda}_{{{\rm{r}}}}^{-2/3}}) (duba siffa 2a a ciki) sashen tattaunawa 5.3.3).Canje-canje masu daidaitawa a cikin sarƙoƙi masu sassauƙa da siffar hanyoyin sadarwar da suka dace kafin da bayan riƙewar biaxial ana nuna su a cikin figs.2b.
Sabanin haka, gels masu fibrous irin su fibrin suna amsawa daban-daban ga riƙewar biaxial.Filayen filaye sun fi dacewa daidai da shugabanci na jujjuyawar matsawa (saboda haka rage nisa tsakanin hanyoyin haɗin giciye), yayin da filayen filaye suka fi dacewa daidai da shugabanci na matsawa suna mikewa a ƙarƙashin aikin ƙarfin roba, yana haifar da gel ɗin zuwa tsawo ( Hoto 1).2c) Tsarin SM, MM da RM maras kyau an kwatanta su ta hanyar nazarin hotunan SEM da CFM (Ƙarin Tattaunawa Sashe na IV da Ƙarin Hoto 9).Ta hanyar ƙayyadaddun modules na roba (E), diamita (d), tsawon bayanin martaba (R0), nisa tsakanin iyakar (L0 ≈ R0) da kusurwar tsakiya (ψ0) na igiyoyi a cikin microgels fibrin mara lalacewa (Ƙarin Teburin 2) - 4), mun gano cewa zaren lankwasawa modules \({k}_{{{{{{\rm{b)))))))))}=\frac{9\pi E{d}^{4}} {4} {\psi } _{0}^{2}{L}_{0}}\) yayi kasa sosai da modulolis dinsa ({k}_{{{{{{{\rm{s}}}}}}}) }} }}=E\frac{\pi {d}^{2}{R}_{0}}{4}\), don haka kb/ks ≈ 0.1 (Ƙarin Tebu na 4).Don haka, a ƙarƙashin yanayin riƙewar gel biaxial, igiyoyin fibrin suna sauƙin lankwasa, amma suna tsayayya da shimfiɗawa.Ana nuna elongation na hanyar sadarwa na filamentous wanda aka yiwa matsi na biaxial a Ƙarin Fig. 17.
Mun haɓaka samfurin affine na ka'idar (Ƙarin Tattaunawa na V da Ƙarin Bayani 10-16) wanda aka ƙaddara ƙaddamar da gel ɗin fibrous daga ma'auni na gida na sojojin na roba da ke aiki a cikin gel kuma yana annabta cewa a cikin wani nau'i mai karfi na biaxial λz - 1 a ƙarƙashin ƙuntatawa
Equation (1) yana nuna cewa ko da a ƙarƙashin ƙarfi mai ƙarfi (\({\lambda }_{{{\mbox{r))))\,\zuwa \,0\)) akwai ɗan ƙaramin gel ɗin fadadawa da nakasar elongation na gaba akan. jikewa λz–1 = 0.15 ± 0.05.Wannan halin yana da alaƙa da (i) \({\hagu({k}_{{{{{\rm{b}}}}}}}}/{k}_{{{{{\rm} {s }}}}}} \ dama)}^{1/2}\) ≈ 0.15−0.4 da (ii) kalmar a madaukai madaidaicin daidai gwargwado \(1{{\mbox{/}}} \sqrt {3}\) don ƙuƙunƙun biaxial masu ƙarfi. Yana da mahimmanci a lura cewa prefactor \ ({\hagu ({k}_{({\mbox{b)))))/{k}_{({\mbox{ s))))\dama)}^{1/ 2}\) ba shi da alaƙa da taurin zaren E, amma an ƙaddara shi ne kawai ta yanayin rabon zaren d/L0 da tsakiyar kusurwar baka. ψ0, wanda yayi kama da SM, MM da RM (Ƙarin Teburin 4).
Don ƙara haskaka bambance-bambancen da ke haifar da 'yanci tsakanin masu sassauƙa da filamentous gels, mun gabatar da rabon biaxial Poisson's ratio \({\nu }_{{({\rm{b)))))) }{{\mbox { =}}}\,\mathop{{\lim}}\liits_{{\lambda}_{{{{({\rm{r}}}}}}\zuwa 1}\ frac{{\ lambda } _{{{{\rm{z}}}}}}}-1}{1-{\lambda }_{{({\rm{r}}}}}}}}}, \) yana bayyana rashin iyaka daidaitawar nau'in gel don amsawa daidai nau'in a cikin radial guda biyu, kuma yana faɗaɗa wannan zuwa manyan nau'ikan iri iri \ rm{b}}}}}}}} ^ {{{{\rm{eff}}}}}} }}=-{{{{{\rm{ln}}}}}}} }{ \lambda } _{z} /{{({\rm{ln)))))))}{\lambda }_{{({\rm{r)))))))}).A kan fig.2d yana nuna \({{{{{\rm{\nu }}}}}}_{{{\rm{b}}}}}}}} ^{{{{\rm { eff }}}}}}}\) don matsewar biaxial iri ɗaya na sassauƙa (kamar agarose) da tauri (kamar fibrin) gels (Ƙarin Tattaunawa, Sashe na 5.3.4), kuma yana nuna alaƙa tsakanin bambance-bambance masu ƙarfi a cikin martani ga ɗaurewa. Ga gels agarose a ƙarƙashin ƙaƙƙarfan ƙuntatawa {\rm{eff}}}}}}}\) yana ƙaruwa zuwa ƙimar asymptotic 2/3, kuma ga fibrin gels yana raguwa zuwa sifili, tun lnλz/lnλr → 0, tunda λz yana ƙaruwa tare da jikewa yayin da λr ke ƙaruwa.Lura cewa a cikin gwaje-gwajen, rufaffiyar microgels suna lalacewa ba tare da kamanceceniya ba, kuma sashinsu na tsakiya yana samun ƙarin matsawa;duk da haka, ƙaddamarwa zuwa babban darajar 1 / λr yana sa ya yiwu a kwatanta gwaji tare da ka'idar don gels maras kyau.
An sami wani bambanci a cikin halayyar sarƙaƙƙiyar gels masu sassauƙa da filamentous gels saboda motsin su akan raguwa.Matsakaicin matsi na ΔPtr, wanda aka saba da shi zuwa gel stiffness S, ya karu tare da ƙara matsawa (Fig. 2e), amma a 2.0 ≤ 1 / λr ≤ 3.5, fibrin microgels ya nuna ƙananan ƙimar ΔPtr / S a lokacin raguwa.Riƙewar microgel na agarose yana haifar da haɓakar matsa lamba na osmotic, wanda ke haifar da shimfidar gel ɗin a cikin madaidaiciyar hanya yayin da ƙwayoyin polymer ke shimfiɗa (Fig. 2b, hagu) da haɓaka matsa lamba ta ΔPtr / S ~ ( 1 / r) 14/317.Akasin haka, an ƙaddara siffar rufaffiyar fibrin microgels ta hanyar ma'auni na makamashi na zaren matsawa na radial da tashin hankali na tsayi, wanda ke haifar da matsakaicin nakasar λz ~\(\sqrt{{k}_{{{{{{{{{{{{{}}} \rm{b))))))))} /{k}_{{{{{\rm{s}}}}}}}.Don 1/λr ≫ 1, ana ƙididdige canjin matsi na juyawa kamar 1 }{{{({\rm{ln)))))"hagu({{\lambda}}}_{{{{\rm}) {r} }}}}}}^{-} 1} \dama)\) (Ƙarin Tattaunawa, Sashe na 5.4), kamar yadda aka nuna ta tsayayyen layin ja a Hoto 2e.Don haka, ΔPtr yana da ƙarancin ƙuntatawa fiye da gels na agarose.Don matsawa tare da 1 / λr> 3.5, haɓaka mai mahimmanci a cikin ƙananan ƙananan filaments da haɗin gwiwar filaments makwabta suna iyakance ƙarin nakasar gel kuma yana haifar da ɓarna na sakamakon gwaji daga tsinkaya (layin ja mai dige a cikin Fig. 2e).Mun kammala cewa ga guda 1/λr da Δ\({P}_{{{{{{\rm{tr}}}}}}}}_{{{{\rm{fibrin}}}))) } }}} \) < ΔP < Δ \ ({P}_{{{{{\rm{tr))))))}}}_{{{\rm{agarose}}}} } } }}\) za a kama agarose gel ta microchannel, kuma gel ɗin fibrin mai tauri iri ɗaya zai ratsa ta.Don ΔP < Δ \ ({P}_{{{{{\rm{tr))))))))_{{{{\rm{fibrin))))))))}\ ), Biyu Dukansu gels za su toshe tashar, amma fibrin gel zai tura zurfi da kuma damfara yadda ya kamata, tare da hana ruwa gudu da kyau.Sakamakon da aka nuna a cikin Hoto 2 ya nuna cewa gel ɗin fibrous zai iya aiki azaman toshe mai tasiri don rage zubar jini ko hana samar da jini ga ciwace-ciwacen daji.
A gefe guda kuma, fibrin ya haifar da ƙwayar ƙwayar cuta wanda ke haifar da thromboembolism, yanayin cututtuka wanda thrombus ya rufe jirgin ruwa a ΔP <ΔPtr, irin su wasu nau'in bugun jini na ischemic (Fig. 3a).Rashin ƙarancin ƙuntatawa da aka haifar da haɓakar fibrin microgels ya haifar da karuwa mai ƙarfi a cikin ƙwayar fibrin na C / C fibrinogen idan aka kwatanta da gels masu sassauƙa, inda C da C fibrinogen ke ƙuntatawa da ƙananan microgels marasa lahani, bi da bi.Polymer maida hankali a cikin gel.Hoto 3b ya nuna cewa fibrinogen C / C a cikin SM, MM, da RM sun karu fiye da sau bakwai a 1 / λr ≈ 4.0, wanda ke haifar da ƙuntatawa da rashin ruwa (Ƙarin Hoto 16).
Misalin tsari na rufewar jijiya ta tsakiya a cikin kwakwalwa.b Ƙaƙƙarwar ƙaƙƙarfan tsaka-tsaki na dangi a cikin fibrin maida hankali a cikin obstructive SM (m jan da'irar), MM (m baƙar fata murabba'i), da RM (m blue triangles).c Zane-zane na gwaji da aka yi amfani da shi don nazarin tsagewar ƙulla fibrin gels.An yi allurar maganin tPA mai kyalli mai kyalli a cikin TBS a saurin gudu na 5.6 × 107 µm3/s da ƙarin digon matsa lamba na 0.7 Pa don tashoshi da ke tsaye da tsayin tsayin daka na babban microchannel.d Pooled multichannel microscopic image na obstructive MM (D0 = 200 µm) a Xf = 28 µm, ΔP = 700 Pa kuma a lokacin rarrabuwa.Layukan dige-dige na tsaye suna nuna matsayi na farko na gefuna na baya da na gaba na MM a tlys = 0. Launuka kore da ruwan hoda sun dace da FITC-dextran (70 kDa) da tPA da aka lakafta tare da AlexaFluor633, bi da bi.e Adadin dangi na lokaci-lokaci na RMs da aka rufe tare da D0 na 174 µm (alwati mai buɗe buɗaɗɗen alwatika), 199 µm (alwati buɗaɗɗen shuɗi), da 218 µm (alwati buɗaɗɗen shuɗi), bi da bi, a cikin microchannel conical tare da Xf = 28 ± 1 µm.sassan suna da ΔP 1200, 1800, da 3000 Pa, bi da bi, da Q = 1860 ± 70 µm3/s.Saitin yana nuna RM (D0 = 218 µm) yana toshe microchannel.f Bambancin lokaci na ƙarar dangi na SM, MM ko RM da aka sanya a Xf = 32 ± 12 µm, a ΔP 400, 750 da 1800 Pa da ΔP 12300 Pa da Q 12300 a cikin yanki na conical na microchannel, bi da bi 24000 da 1800 µm3. /s.Xf yana wakiltar gaban gaban microgel kuma yana ƙayyade nisa daga farkon raguwa.V(tlys) da V0 sune ƙarar ɗan lokaci na microgel lysed da ƙarar microgel mara damuwa, bi da bi.Launukan halayen sun dace da launuka a cikin b.Baƙaƙen kibau akan e, f sun dace da ƙarshen lokacin kafin wucewar microgels ta hanyar microchannel.Ma'auni a cikin d, e shine 100 µm.
Don bincika tasirin ƙuntatawa akan raguwar kwararar ruwa a cikin gels na toshewa, mun yi nazarin lysis na SM, MM, da RM da aka shiga tare da wakili na thrombolytic tissue plasminogen activator (tPA).Hoto 3c yana nuna ƙirar gwaji da aka yi amfani da su don gwaje-gwajen lysis. A ΔP = 700 Pa (<ΔPtr) da kuma kwararar ruwa, Q = 2400 μm3 / s, na Tris-buffered saline (TBS) gauraye da 0.1 mg / mL na (fluorescein isothiocyanate) FITC-Dextran, microgel ya rufe microchannel tapered. yanki. A ΔP = 700 Pa (<ΔPtr) da kuma kwararar ruwa, Q = 2400 μm3 / s, na Tris-buffered saline (TBS) gauraye da 0.1 mg / mL na (fluorescein isothiocyanate) FITC-Dextran, microgel ya rufe microchannel tapered. yanki. При ΔP = 700 Па (<ΔPtr) da скорости потока, Q = 2400 мкм3/с сцеинизотиоцианата) FITC-декстрана, микрогель перекрывал сужающийся m. A ΔP = 700 Pa (<ΔPtr) da kuma raguwa, Q = 2400 µm3 / s, na Tris buffered saline (TBS) gauraye da 0.1 mg / mL (fluorescein isothiocyanate) FITC-dextran, microgel ya rufe microchannel mai haɗuwa.yanki.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) da скорости потока Q = 2400 мкм3/с Конические области микроканалов. Microgels toshe lokacin da Tris buffered saline (TBS) ya haɗu tare da 0.1mg/mL (fluorescein isothiocyanate) FITC-dextran a ΔP = 700 Pa (<ΔPtr) da ƙimar kwarara Q = 2400 µm3 / s Conical yankuna na microchannels.Matsayin gaba Xf na microgel yana ƙayyade nisa daga wurin raguwa na farko X0.Don haifar da lysis, an allurar maganin tPA mai kyalli a cikin TBS daga tashar da ke a kai tsaye zuwa doguwar axis na babban microchannel.
Lokacin da maganin tPA ya kai MM occlusal, gefen baya na microgel ya zama mara kyau, yana nuna cewa fibrin cleavage ya fara a lokacin tlys = 0 (Fig. 3d da Ƙarin Hoto 18).A lokacin fibrinolysis, tPA mai lakabin rini ya taru a cikin MM kuma yana ɗaure zuwa igiyoyin fibrin, wanda ke haifar da karuwa a hankali a cikin tsananin launin ruwan hoda na microgels.A tlys = 60 min, MM kwangilar saboda rushewar sashinta na baya, kuma matsayin babban gefenta Xf yana canzawa kadan.Bayan 160 min, MM mai karfi da aka yi kwangila ya ci gaba da yin kwangila, kuma a tlys = 161 min, an yi ta raguwa, ta haka ne ya dawo da ruwa mai gudana ta hanyar microchannel (Fig. 3d da Ƙari na 18, shafi na dama).
A kan fig.3e yana nuna raguwar matsakaicin matsakaicin lokaci na lysis a cikin ƙarar V (tlys) wanda aka daidaita zuwa ƙarar farko na V0 na microgels fibrin daban-daban.CO tare da D0 174, 199, ko 218 µm an sanya shi a cikin microchannel tare da ΔP 1200, 1800, ko 3000 Pa, bi da bi, da Q = 1860 ± 70 µm3 / s don toshe microchannel (Fig. 3e, inset).abinci mai gina jiki.A hankali microgels suna raguwa har sai sun yi ƙanƙanta don wucewa ta tashoshi.Rage ƙimar CO mai mahimmanci tare da diamita mafi girma na farko yana buƙatar tsawon lokacin lysis.Saboda irin wannan kwarara ta RMs daban-daban, tsagewa yana faruwa a daidai wannan ƙimar, yana haifar da narkewar ƙananan juzu'i na RMs mafi girma da jinkirin jujjuyawar su.A kan fig.3f yana nuna raguwar dangi a cikin V (tlys)/V0 saboda rarrabuwa don SM, MM, da RM a D0 = 197 ± 3 µm da aka tsara azaman aikin tlys.Don SM, MM da RM, sanya kowane microgel a cikin microchannel tare da ΔP 400, 750 ko 1800 Pa da Q 12300, 2400 ko 1860 µm3/s, bi da bi.Kodayake matsin lamba da aka yi wa SM ya kasance sau 4.5 ƙasa da na RM, gudana ta hanyar SM ya fi sau shida ƙarfi saboda mafi girman haɓakar SM, kuma raguwar microgel ya ragu daga SM zuwa MM da RM. .Misali, a tlys = 78 min, SM galibi sun narkar da su kuma sun yi gudun hijira, yayin da MM da PM suka ci gaba da toshe microchannels, duk da riƙe 16% da 20% na ainihin ƙarar su, bi da bi.Wadannan sakamakon suna ba da shawarar mahimmancin ƙaddamar da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta.
Don haka, aikinmu yana nuna gwaji da ka'idar tsarin da filamentous gels ke amsawa ga tsare biaxial.Halin fibrous gels a cikin iyakataccen sararin samaniya an ƙaddara ta hanyar asymmetry mai ƙarfi na ƙarfin ƙarfin ƙarfin filaments (mai laushi a cikin matsawa da wuya a cikin tashin hankali) kuma kawai ta hanyar rabo da curvature na filaments.Wannan halayen yana haifar da ƙarancin haɓakar fibrous gels ɗin da ke ƙunshe a cikin kunkuntar capillaries, rabon su na Poisson na biaxial yana raguwa tare da ƙara matsawa da ƙarancin haske.
Tunda ana amfani da ƙunshewar biaxial na ɓangarorin nakasa mai laushi a cikin fasahohi da yawa, sakamakonmu yana haɓaka haɓaka sabbin kayan fibrous.Musamman, riƙewar biaxial na gels na filamentous a cikin kunkuntar capillaries ko tubes yana haifar da haɓakar ƙarfin su da raguwa mai ƙarfi a cikin haɓaka.Ƙarfin ƙaƙƙarfan hana ruwa mai gudana ta hanyar gels fibrous occlusive yana da fa'ida idan aka yi amfani da shi azaman matosai don hana zub da jini ko rage samar da jini zuwa malignancies33,34,35.A gefe guda, raguwar kwararar ruwa ta hanyar gel ɗin fibrin na occlusal, ta haka yana hana thrombus lysis mai tsaka-tsaki, yana ba da alamar jinkirin lysis na clots na occlusal [27, 36, 37].Tsarin ƙirar mu shine mataki na farko don fahimtar abubuwan da ke tattare da amsawar injina na fibrous biopolymer hydrogels zuwa riƙe biaxial.Haɗa ƙwayoyin jini ko platelets cikin gels ɗin fibrin masu hana su zai shafi halayen ƙuntatawa 38 kuma zai zama mataki na gaba na fallasa ɗabi'ar mafi hadaddun tsarin ilimin halitta.
Reagents da aka yi amfani da su don shirya microgels na fibrin da ƙirƙira na'urorin MF an bayyana su a cikin Ƙarin Bayani (Ƙarin Hanyoyin Sashe na 2 da 4).An shirya microgels na Fibrin ta hanyar kwaikwaya gaurayawan mafita na fibrinogen, Tris buffer da thrombin a cikin na'urar MF mai gudana mai gudana, sannan kuma gelation na digo.Maganin fibrinogen na Bovine (60 mg / ml a cikin TBS), Tris buffer da maganin thrombin bovine (5 U / ml a cikin 10 mM CaCl2 bayani) an gudanar da su ta amfani da famfunan sirinji masu zaman kansu guda biyu (PhD 200 Harvard Apparatus PHD 2000 Syring Pump).don toshe MF, Amurka).F-man ci gaba da lokaci mai dauke da 1 wt.% toshe copolymer PFPE-P(EO-PO) -PFPE, an gabatar da shi cikin sashin MF ta amfani da famfon sirinji na uku.Ana tattara ɗigon da aka kafa a cikin na'urar MF a cikin bututu mai centrifuge 15 ml mai ɗauke da F-man.Sanya bututun a cikin wanka na ruwa a 37 ° C na awa 1 don kammala fibrin gelation.FITC mai lakabin fibrin microgels an shirya su ta hanyar haɗa fibrinogen na bovine da FITC mai lakabin fibrinogen ɗan adam a cikin ma'aunin nauyi 33:1, bi da bi.Hanyar daidai yake da shirye-shiryen microgels na fibrin.
Canja wurin microgels daga mai F zuwa TBS ta hanyar rage tarwatsawa a 185 g na 2 min.An watsar da microgels da aka haɗe a cikin mai F gauraye da 20 wt.% perfluorooctyl barasa, sa'an nan kuma tarwatsa a hexane dauke da 0.5 wt.% Span 80, hexane, 0.1 wt.% Triton X a cikin ruwa da TBS.A ƙarshe, an tarwatsa microgels a cikin TBS mai ɗauke da 0.01 wt% Tween 20 kuma an adana su a 4 ° C na kusan makonni 1-2 kafin gwaje-gwaje.
An bayyana ƙirƙira na'urar MF a cikin Ƙarin Bayani (Ƙarin Hanyoyin Sashe na 5).A cikin gwaji na yau da kullun, ƙimar ƙimar ΔP ta ƙayyade girman dangi na tafkunan da aka haɗa kafin da kuma bayan na'urar MF don gabatar da microgels tare da diamita na 150
Ana samun bayanan da ke goyan bayan sakamakon wannan binciken daga mawallafa daban-daban akan buƙata.Hotunan Raw SEM na fibrin gels, Hotunan TEM masu kyau na fibrin gels kafin da kuma bayan inoculation, da kuma mahimman bayanai na shigarwa don Figures 1 da 2. 2 da 3 an bayar da su a cikin albarkatun bayanai.Wannan labarin yana ba da bayanan asali.
Litvinov RI, Peters M., de Lange-Loots Z. da Weisel JV fibrinogen da fibrin.A cikin Macromolecular Protein Complex III: Tsarin da Aiki (ed. Harris, JR da Marles-Wright, J.) 471-501 https://doi.org/10.1007/978-3-030-58971-4_15 ( Springer da Cham, 2021).
Bosman FT da Stamenkovich I. Tsarin aiki da abun da ke ciki na matrix extracellular.J. Pasol.200, 423-428 (2003).
Prince E. da Kumacheva E. Zane da aikace-aikace na wucin gadi biomimetic fiber hydrogels.National Matt Red.4, 99-115 (2019).
Broedersz, CP & Mackintosh, FC Modeling Semi-m polymer networks.Firist Mod.ilimin lissafi.86, 995-1036 (2014).
Khatami-Marbini, H. da Piku, KR Mechanical modeling of semi-m bioopolymer networks: rashin nakasar affin da kasancewar abubuwan dogaro mai tsayi.A Ci gaba a cikin Soft Matter Mechanics 119-145 (Springer, Berlin, Heidelberg, 2012).
Vader D, Kabla A, Weitz D, da Mahadevan L. Matsalolin da ke haifar da alignment na gels collagen.PLoS Daya 4, e5902 (2009).
Storm S., Pastore JJ, McKintosh FS, Lubensky TS, da Gianmi PA Rashin daidaituwa na biogels.Yanayin 435, 191-194 (2005).
Likup, AJ Stress yana sarrafa hanyoyin sadarwar collagen.tsari.Kwalejin Kimiyya ta Kasa.ilimin kimiyya.US 112, 9573-9578 (2015).
Janmi, PA, et al.Rashin damuwa na al'ada mara kyau a cikin gels biopolymer mai sassaucin ra'ayi.Almajiri na kasa.6, 48-51 (2007).
Kang, H. et al.Ƙunƙarar da ba ta kan layi ba na hanyoyin sadarwa na fiber mai ƙarfi: ƙwanƙwasawa, damuwa na al'ada mara kyau, da daidaitawar fiber a cikin fibrin gels.J. Physics.ChemicalV. 113, 3799-3805 (2009).
Gardel, ML et al.Halayen roba na hanyoyin sadarwa na actin masu alaƙa da ɗaure.Kimiyya 304, 1301-1305 (2004).
Sharma, A.Makanikai marasa kan layi na hanyoyin sadarwa na fiber optic masu sarrafa iri tare da kulawa mai mahimmanci.Ilimin kimiyyar lissafi na kasa.12, 584-587 (2016).
Wahabi, M. et al.Ƙirƙirar hanyoyin sadarwar fiber ƙarƙashin uniaxial prestressing.Taushi Al'amari 12, 5050-5060 (2016).
Wufsus, AR, Macera, NE & Neeves, KB Bloot clot hydraulic permeability a matsayin aikin fibrin da yawan platelet.nazarin halittu.Jaridar 104, 1812-1823 (2013).
Li, Y. et al.Halin halayen hydrogels yana iyakance ta kunkuntar capillaries.ilimin kimiyya.Gidan 5, 17017 (2015).
Liu, X., Li, N. & Wen, C. Tasirin nau'ikan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan cututtukan hai da ƙaiƙayi da ƙazamin ƙazamin elastography.PLoS Daya 12, e0179103 (2017).
Mfoumou, E., Tripette, J., Blostein, M. & Cloutier, G. A cikin vivo ƙididdigewa na lokaci-lokaci induration na jini clots ta yin amfani da shear kalaman duban dan tayi hoto a cikin zomo venous thrombosis model.thrombus.tankin ajiya.133, 265-271 (2014).
Weisel, JW & Nagaswami, C. Kwamfuta Kwamfuta na fibrin polymerization kuzarin kawo cikas dangane da electron microscopy da turbidity lura: jini tsarin da taro ana sarrafa kinetically.nazarin halittu.Jaridar 63, 111-128 (1992).
Ryan, EA, Mokros, LF, Weisel, JW da Lorand, L. Tsarin tushen fibrin clot rheology.nazarin halittu.J. 77, 2813-2826 (1999).
Lokacin aikawa: Fabrairu-23-2023