Artificial Organ Experts tham txog Txoj Kev Loj Hlob, Kev Sib Tw thiab Lub Sijhawm Ntawm Lub raum Artificial

Tam sim no, lub raum tsis ua haujlwm tau dhau los ua teeb meem kev noj qab haus huv tseem ceeb thoob ntiaj teb. Raws li 2021 cov ntaub ntawv, kwv yees li 4.7 lab tus neeg mob tau txais kev kho lub raum hloov. Vim tsis muaj cov khoom siv raum thiab lwm yam, feem ntau cov neeg mob lub raum tsis ua haujlwm tau txais kev kho lub raum hloov nrog hemodialysis thiab peritoneal dialysis, tab sis ob qho tib si kev lim ntshav muaj lawv qhov tsis zoo. Hemodialysis muaj qhov tsis zoo ntawm lub neej thiab muaj kev tuag siab heev. Qhov zoo ntawm lub neej ntawm peritoneal dialysis yog siab, thiab kev tuag tus nqi kuj tsawg, tab sis tus nqi yog siab, thiab tom qab ob peb xyoos, peritoneal dialysis cov neeg mob yuav tsum tau hloov mus rau hemodialysis vim muaj tej yam xws li kev tsis ua hauj lwm. Raws li cov laj thawj saum toj no, tib neeg ib txwm cia siab tias yuav tsim lub raum tsis zoo, uas tuaj yeem tso cov neeg mob los ntawm qhov tsis txaus ntawm kev lim ntshav, thiab ua kom muaj kev ywj pheej ntawm cov neeg mob kom lawv muaj peev xwm txaus siab rau lub neej zoo thiab muaj cai ua haujlwm.

Nyem rau cistanche tubulosa capsules rau kab mob raum

Thaum Lub Rau Hli 5, 2023, Nature Reviews Nephrology tau luam tawm kev tshuaj xyuas los ntawm cov kws tshaj lij los ntawm European Artificial Kidney Development Team thiab Artificial Organ Development Team. Tom qab tshuaj xyuas cov qauv qauv tam sim no ntawm lub raum dag, cov kws tshaj lij tau muab ob lub raum ua kom zoo nkauj rau hauv ob pawg, lub tshuab ntxuav lub cev, thiab lub raum bioartificial. Ob hom kev tsim lub raum no muaj lawv qhov zoo thiab qhov tsis zoo, thiab cov cib fim thiab kev sib tw ua ke. Tsis tas li ntawd, cov cuab yeej tshiab semi-permeable membrane yuav pab txhim kho lub raum dag thiab txawm tias txhim kho cov tshuab hemodialysis uas twb muaj lawm.

Wearable Dialysis Tshuab

Qhov mob taw tes ntawm kev siv lub tshuab lim ntshav yog qhov tseem ceeb heev, uas yog kev tsim kho ntawm dialysate. Siv cov tshuaj hemodialysis ua piv txwv, 4 teev ntawm kev lim ntshav yuav tsum tau 120-150L ntawm dialysate. Cov neeg mob tsis tuaj yeem nqa dialysate ntau nrog lawv. Yog li ntawd, lub tshuab hnav khaub ncaws yuav tsum siv lub cuab yeej uas txuas ntxiv rov tsim dua dialysate hauv lub kaw lus kaw.

Tam sim no, dialysate regeneration li siv nyob rau hauv lub wearable dialysis tshuab feem ntau muaj xws li cation exchangers/membranes, xws li polystyrene resins. Lawv tshem tawm cations xws li potassium, sodium, thiab hydrogen ions. Thiab anions kuj raug tshem tawm los ntawm ntau txoj kev, xws li zirconium oxide / polystyrene puag nrog immobilized hlau ions (xws li hlau los yog lanthanum) los hloov phosphate rau hauv paus. Cov txheej txheem saum toj no tuaj yeem kho tus nqi pH ntawm dialysate, yog li rov ua kom tus neeg mob lub acid-base thiab ion tshuav nyiaj li cas. Hauv kev tshem tawm cov organic solutes, txoj kev siv feem ntau yog activated carbon adsorption. Cov kev tshawb fawb tau pom tias 81 feem pua ​​​​ntawm cov organic uremic solutes pom nyob rau hauv dialysate yog adsorbed los ntawm activated carbon, nrog rau cov protein-bound solutes.

Txawm li cas los xij, cov pa roj carbon activated tsis tuaj yeem siv rau kev tshem tawm urea vim tias qhov sib txuam ntawm cov pa roj carbon activated rau urea tsawg heev ({{0}}}.1–0.2 mmol / g feem ntau), thiab cov txiaj ntsig ntawm urea siab dua lwm yam. organic uremic kua. Yog li, lwm txoj kev yuav tsum tau siv rau kev tshem tawm, xws li enzymatic hydrolysis, electrochemical decomposition, thiab adsorption.

1 Enzymatic hydrolysis

Urease hydrolysis yog ib lub tswv yim zoo heev, 30 ~ 50g ntawm urease nquag tuaj yeem tshem tawm tag nrho cov urea uas tsim tawm thaum lub sij hawm 4h dialyzes. Txawm li cas los xij, qhov decomposition ntawm urea tsim ammonium, uas yog tshuaj lom ntau dua. Zirconium phosphate tuaj yeem khi ammonium, tab sis tib lub sijhawm, zirconium phosphate tuaj yeem tshem tawm tag nrho calcium, magnesium, thiab potassium ions hauv dialysate, yuav tsum tau rov ua dua. Txawm li cas los xij, qhov no ua rau qhov loj thiab qhov hnyav ntawm lub tshuab lim ntshav. Yog tias hom tshiab ntawm semipermeable membrane tuaj yeem tsuas yog adsorb ammonium, txoj kev enzymatic hydrolysis tuaj yeem siv dav.

2 Electrochemical decomposition

Raws li txoj cai, electrochemical decomposition tuaj yeem tso cai hloov pauv ntawm urea rau nitrogen thiab carbon dioxide. Ob yam khoom no tsis muaj tshuaj lom thiab tuaj yeem tawm ncaj qha rau hauv qhov chaw. Txawm li cas los xij, cov txheej txheem electrochemical decomposition kuj tseem tuaj yeem hloov cov tshuaj chloride ions hauv cov ntshav los ua cov tshuaj hypochlorite, thiab oxidation ntxiv tuaj yeem tsim nitrite, nitrate, ammonium, thiab lwm yam. Tsis tas li ntawd, qhov hluav taws xob thiab lub zog yuav tsum tau siv rau electrolysis kuj yog cov ntsiab lus mob rau cov khoom siv lim ntshav.

Sim lwm cov ntaub ntawv electrode zoo li txhim kho cov ntsiab lus mob tau hais tseg. Graphite, npib tsib xee-tooj ​​hlau alloy, thiab titanium dioxide yog tag nrho cov kev daws teeb meem zoo. Nyob rau hauv nruab nrab los yog me ntsis alkaline tej yam kev mob, cov saum toj no electrodes tuaj yeem oxidize / electrolyze urea, tsim cov tshuaj lom tsawg. Txawm li cas los xij, seb cov electrodes saum toj no tuaj yeem ua tau zoo dua hauv qhov nyuaj thiab sib txawv thiab siv dialysate ib puag ncig tseem xav tau kev tshawb fawb ntxiv.

3 ua adsorption

Tam sim no, adsorption zoo li yog txoj hauv kev zoo tshaj plaws los daws cov urea hauv dialysate. Adsorption tuaj yeem muab faib ua cov tshuaj adsorption (covalent daim ntawv cog lus) thiab lub cev adsorption (dipole kev sib cuam tshuam los ntawm hydrogen bonding), uas cov tshuaj adsorption ruaj khov, irreversible tab sis qeeb; lub cev adsorption yog ceev tab sis tsis ruaj khov. Tam sim no, qee cov alloys thiab cov ntaub ntawv tshiab tuaj yeem txhim kho cov ntsiab lus mob saum toj no. Chitosan yog ib yam khoom uas adsorbs urea los ntawm lub cev adsorption. Txawm hais tias lub zog khi ntawm chitosan adsorption tsawg tsawg (tsuas yog 0.2mmol / g), tom qab tsim ib qho nyuaj nrog cov hlau ions, xws li tooj liab ions, lub zog khi tuaj yeem nce mus rau 4.4mmol / g.

Tsis tas li ntawd, qhov sib xyaw hauv qab daus daim nyias nyias (MMM) muaj li ntawm polystyrene ninhydrin, polyethersulfone, thiab polyvinylpyrrolidone kuj pom tias muaj kev sib khi zoo. Txoj cai adsorption ntawm MMM yog tshuaj adsorption ntxiv rau lub cev adsorption, nrog tus nqi siab thiab ruaj khov. Nws yog tsim nyog sau cia tias lub peev xwm adsorption ntawm MMM yog siab tshaj ntawm 70 degree. Yog li ntawd, yuav ua li cas kom MMM muaj peev xwm adsorption ntau dua ntawm 37 degree tseem xav tau kev kawm ntxiv.

bioartificial raum

Lub raum bioartificial (BAK) yog ib lub raum dag uas ua ke nrog biology thiab lub cev chemistry. BAK muaj lub raum proximal hlwb thiab muaj kev thauj mus los, metabolism, thiab endocrine kev ua ub no, uas tuaj yeem ua raws li kev ua haujlwm ntawm tib neeg lub raum tubules. Tsis zoo li cov tshuab lim dej uas siv tau, BAK yog ib feem ua haujlwm los ntawm cov txheej txheem lom (hlwb). Cov kev tshawb fawb ntawm cov neeg mob uas mob raum raug mob (AKI) qhia tias BAK tuaj yeem txhim kho qhov ciaj sia taus ntawm cov neeg mob. Txawm li cas los xij, qhov teeb meem loj tshaj plaws nrog BAK yog qhov tau txais thiab khaws cov hlwb. Yog tias cov tsev kho mob lossis cov tuam txhab muaj feem cuam tshuam tsis tuaj yeem daws cov kev tsim khoom, kev thauj mus los, kev khaws cia, thiab kev faib tawm zoo ntawm cov hlwb saum toj no, kev nkag tau ntawm BAK yuav tsis tshua muaj. Tsis tas li ntawd, nws tseem tuaj yeem kawm txog kev ua kom lub neej ntev ntawm cov hlwb kom txo tau cov nqi ntawm kev siv BAK.

Lus Cim: Tus neeg mob cov ntshav ua ntej dhau los ntawm cov cuab yeej siv tshuaj tua kab mob kom tshem tawm albumin, me me molecules, thiab uremic toxins khi rau cov protein, thiab tom qab ntawd nkag mus rau cov khoom siv tshuaj lom neeg. Hauv cov khoom siv bioreaction, tubular cells reabsorb thiab thauj qee cov tshuaj, rov qab albumin thiab lwm yam khoom muaj txiaj ntsig rau lub cev mus rau hauv cov ntshav.

Tsis tas li ntawd, qhov kev sib tw ntawm BAK yog miniaturization. Tam sim no, hnav khaub ncaws BAK tau ua tiav thawj zaug hauv cov qauv tsiaj (kidneyless yaj / npua). Hauv cov qauv yaj uas tsis muaj lub raum, tsis muaj kev tsis lees paub tshwm sim hauv cov yaj, thiab lub sijhawm muaj sia nyob zoo yog ntau tshaj 7 hnub. Hauv cov qauv npua, tom qab kev cog qoob loo ntawm BAK, cov npua tsis muaj kev tsis lees paub, thiab cov nyhuv curative zoo tagnrho.

Tshiab Dialysis Membrane

Ib yam li aerospace thev naus laus zis yuav kawg txhim kho pej xeem thev naus laus zis. Lub raum dag tsim tsim rau cov xwm txheej huab cua (miniaturization, kev siv hluav taws xob tsawg, me me ntawm dialysate, thiab lwm yam) nws thiaj li txhawb kev txhim kho ntawm kev lim ntshav thiab ua kom zoo dua cov tshuab hemodialysis uas twb muaj lawm.

1 polymer zaj duab xis

Txhawm rau ua kom lub neej ntev ntawm lub tshuab lim dej thiab txo qhov kev xav tau ntawm cov neeg mob los hloov qhov chaw ntawm lub tshuab lim dej. Cov kws tshawb fawb tau pom zoo nrog cov biocompatibility ntawm cov tshuaj lim dej. Polymer membranes yog ib lub tswv yim zoo. Polyvinylidene fluoride membrane hloov los ntawm polyvinyl cawv thiab chitosan tuaj yeem txhim kho biocompatibility zoo. Lwm txoj kev xav yog tias ntxiv argatroban lossis hydrophilic tshuaj rau polysulfone daim nyias nyias tuaj yeem txo qhov kev pheej hmoo ntawm thrombosis thiab ua kom muaj kev nyab xeeb ntawm hemodialysis.

2-nanometer silicon puag zaj duab xis

Ib txwm silicon-raws li daim nyias nyias muaj cov biocompatibility tsis zoo, lub neej ua haujlwm luv luv, thiab muaj qhov ua rau thrombus tsim. Txawm li cas los xij, nrog kev txhim kho ntawm cov cuab yeej siv hluav taws xob, tshwj xeeb tshaj yog cov tshuab photolithography, nws tsis yooj yim rau kev tsim cov yeeb yaj kiab nano-silicon. Nanosilica-raws li daim nyias nyias tuaj yeem yog kaj ntug hauv vivo hemodialysis li. Xyoo 2022, nano-silicon-based membrane hemodialyzer tau ua tiav hauv npua. Qhov no hemodialyzer tuaj yeem ua hemodialysis tau. Nws cov creatinine thiab urea clearance tus nqi sib npaug rau cov tsoos fiber ntau dialyzers, tab sis cov ntshav txaus tsuas yog 1/20. Yog li ntawd, lub twj tso kua mis yog tsis tas yuav tsum tau. Ntshav ntws yog ua tiav los ntawm physiological arterial-venous siab sib txawv. Tsis tas li ntawd, hom hemodialyzer no tuaj yeem ua ke nrog cov ntsuas hluav taws xob thiab lub tshuab hluav taws xob micro, ua ke nrog 5 × 5m2 silicon nti, uas tuaj yeem tsim kom muaj ntau qhov ntsuas kev kho mob los saib xyuas qhov xwm txheej ntawm hemodialysis hauv lub sijhawm, uas yog qhov tsim nyog. mus rau kev kho mob tus kheej.

3 ion reabsorbed

AWEDI yog ib qho ion reabsorbed uas sib txuas cov ion txauv resin, ion txauv membrane, thiab siv hluav taws xob kom ua tiav cov kev xaiv ion reabsorption, zoo ua haujlwm ntawm lub raum tubules. Cov kev tshawb fawb tau pom tias AWEDI system tuaj yeem rov nqus tau cov sodium, potassium, magnesium, thiab calcium ions, thiab txawm tias qabzib tuaj yeem rov nqus tau. Txawm li cas los xij, AWEDI system tseem ntsib peb qhov kev sib tw. Ua ntej, AWEDI system muaj lub peev xwm tsis zoo los tshem tawm cov co toxins nrog lub cev hnyav> 180 Da; Qhov thib ob, qhov kev thauj mus los ntawm ion yog cuam tshuam nrog voltage. Yog tias qhov hluav taws xob siab dhau lawm, dej yuav raug faib ua hydrogen thiab oxygen; Yog tias qhov hluav taws xob tsawg dhau lawm, qhov kev ua haujlwm ntawm reabsorption yuav tsis siab; Thaum kawg, cov ion xaiv ntawm cov muaju sib txawv muaj qhov sib txawv loj (txog 42 feem pua), thiab qhov sib txawv no muaj feem xyuam rau qhov loj ntawm AWEDI, dialysate concentration, pH tus nqi, thiab txawm tias qhov voltage.

Tus qauv ntawm lub raum dag / hnav lub tshuab lim ntshav

Tam sim no, PAKs thiab WAK yog cov qauv ntawm cov khoom siv lub raum / hnav lub tshuab lim ntshav uas tau siv rau hauv kev tshawb fawb soj ntsuam, cov uas WAK yog lub npe nrov tshaj plaws. Qhov hnyav ntawm WAK yog li 5 kg. Cov kev tshawb fawb soj ntsuam tau lees paub tias WAK tuaj yeem ua haujlwm tsis tu ncua rau 4 ~ 8 teev lossis txawm tias 24 teev. WAK tuaj yeem muab kev lim dej zoo hauv 24 teev, thiab qhov tshem tawm ntawm urea, creatinine, thiab phosphorus yog 17 ± 10, 16 ± 8, thiab 15 ± 9ml / min, raws li. Txawm li cas los xij, thaum lub sijhawm 24-h kev tshawb fawb soj ntsuam, cov pa roj carbon dioxide ntau dhau hauv cov dialysate thiab coagulation nyob rau hauv lub extracorporeal Circuit Court ua rau qhov kev txiav txim thaum ntxov.

If hemodialysis is not considered, automatic WAK (AWAK) is a smaller (2kg) peritoneal dialysis device, which can significantly reduce the consumption of dialysate, and most adult patients can carry it with them. A study in 2022 showed that in 14 patients with peritoneal dialysis, AWAK could work 10.5 hours a day for 3 consecutive days. The study showed that AWAK significantly cleared urea (20.8 to 14.9mm; P = 0.001), creatinine (976 to 668uM; P = 0.001), and phosphorus (1.7 to 1.5mM; P = 0.03), and weekly peritoneal Urea clearance index, Kt/V>1.7. Tsis muaj qhov tshwm sim tsis zoo tshwm sim hauv cov neeg mob. Txawm hais tias qee tus neeg mob tau ntsib kev tsis xis nyob hauv plab, lawv tau zoo siab tom qab tso dej ntawm dialysate lossis defecation.

Lwm 4 PAK cov qauv tau raug tso tawm thiab cov kev tshawb fawb soj ntsuam ntsig txog tab tom pib. Txawm li cas los xij, qhov hnyav ntawm PAK cov qauv no ntau dua lossis sib npaug li 10kg. Yog li ntawd, nyob rau hauv cov nqe lus ntawm portability, nws zoo ib yam li WAK.

Feem ntau, cov qauv ntawm lub raum dag thiab BAK tau tshwm sim ib zaug. Txawm hais tias muaj ntau yam kev sib tw, nrog rau kev nce qib ntawm cov tshuaj thiab lwm yam kev qhuab qhia, cov kev cov nyom no yuav daws tau ib qho tom qab. Tsis tas li ntawd, cov khoom siv dag zog tuaj yeem muab ntxiv rau hauv micro-sensing systems (xws li kev soj ntsuam cov kua dej, thiab cov ntshav tshwj xeeb), thiab ua ke nrog cov thev naus laus zis xws li AI los tsim cov lus qhia kho mob rau tus kheej.

Cov ntaub ntawv:

1. Ramada DL, de Vries J, Vollenbroek J, et al. Portable, wearable, thiab implantable dag lub raum systems: xav tau kev pab, lub cib fim, thiab cov kev cov nyom. Nat Rev Nephrol. 2023 Lub Rau Hli 5:1–10.