Cardarine ntsiav tshuaj

Angiogenesis yog ib qho tseem ceeb rau kev ua tiav ntawm cov ntaub so ntswg engineering scaffolds, kom ntseeg tau cov khoom noj khoom haus rau cov hlwb hauv scaffold thiab tshem tawm cov khib nyiab. Yog tias tsis muaj vascular network txaus, cov hlwb hauv scaffold yuav tuag vim hypoxia thiab cov khoom noj tsis txaus, ua rau cov ntaub so ntswg kho tsis ua haujlwm. Los ntawm kev ua kom PPAR δ, vascular endothelial hlwb tuaj yeem raug ntxias kom nthuav tawm vascular endothelial kev loj hlob zoo (VEGF) thiab cov txheej txheem fibroblast loj hlob (bFGF). VEGF yog ib qho tseem ceeb tshaj plaws hauv kev txhawb nqa angiogenesis, vim nws tuaj yeem txhawb kev loj hlob, tsiv teb tsaws, thiab lumen tsim ntawm endothelial hlwb;

BFGF muaj ntau yam kev ua ub no, uas tuaj yeem txhawb kev loj hlob ntawm vascular endothelial hlwb thiab vascular du leeg hlwb, ntxiv dag zog rau cov hlab ntsha.

Kev thauj khoom mus rau polylactic acid hydroxyacetic acid copolymer (PLGA) scaffold tuaj yeem txhim kho vascularization efficiency ntawm scaffold. PLGA yog cov khoom siv polymer nrog zoo biocompatibility thiab degradability, feem ntau siv rau hauv kev npaj cov ntaub so ntswg engineering scaffolds.

Hauv kev sim tsiaj, PLGA scaffolds loaded nrog GW-501516 tuaj yeem tsim lub network neovascularization sai dua tom qab cog. Cov hlab ntsha uas tau tsim tshiab no muab cov khoom noj txaus txaus thiab cov pa oxygen rau kev kho cov ntaub so ntswg, ua rau cov hlwb hauv lub scaffold kom muaj sia nyob thiab loj hlob zoo dua, yog li ua kom cov txheej txheem ntawm cov ntaub so ntswg rov ua dua thiab kho dua. Piv txwv li, hauv cov qauv nas ntawm daim tawv nqaij tsis zoo, kev siv PLGA scaffolds loaded nrog cov tshuaj no ua rau kom cov tawv nqaij kho sai thiab txhim kho kev kho kom zoo dua qub piv rau unloaded scaffolds.

Lub extracellular matrix (ECM) yog ib qho tseem ceeb ntawm cov ntaub so ntswg engineering scaffolds, muab ib tug microenvironment rau cell txuas, proliferation, thiab sib txawv. Qhov muaj pes tsawg leeg thiab cov qauv ntawm ECM ua lub luag haujlwm tseem ceeb hauv kev tswj hwm qhov kev ua haujlwm ib txwm muaj thiab morphology ntawm cov ntaub so ntswg. Nws tuaj yeem txhawb kev qhia ntawm collagen thiab elastin hauv fibroblasts. Collagen yog cov protein ntau tshaj plaws hauv ECM, uas ua rau cov ntaub so ntswg muaj zog thiab tawv; Elastin muab cov ntaub so ntswg elasticity thiab muaj peev xwm tiv taus qee yam deformations yam tsis muaj rupture.

Los ntawm kev txhim kho cov kev qhia ntawm ob cov proteins no, cov neeg kho tshuab lub zog thiab biocompatibility ntawm scaffold tuaj yeem txhim kho, ua kom ze rau cov yam ntxwv ntawm tib neeg cov ntaub so ntswg.

Tsis tas li ntawd, nws tuaj yeem cuam tshuam kev ua haujlwm ntawm matrix metalloproteinases (MMPs). MMP yog ib hom enzyme uas tuaj yeem degrade ECM Cheebtsam. Raws li ib txwm muaj, kev ua haujlwm ntawm MMP tau tswj hwm nruj kom tswj tau qhov sib npaug ntawm ECM.

Tab sis nyob rau hauv tej yam pathological tej yam kev mob, xws li o los yog qog nqaij hlav, cov kev ua ntawm MMP yuav ua tau txawv txav, ua rau ntau degradation ntawm ECM thiab cuam tshuam cov ntaub so ntswg kho thiab rov tsim dua tshiab. Los ntawm inhibiting qhov kev ua ntawm MMP thiab txo qhov degradation ntawm ECM, lub neej ntawm stent yuav txuas ntxiv. Piv txwv li, nyob rau hauv daim tawv nqaij engineering, sib txuas GW-501516 nrog collagen scaffolds yuav txhawb fibroblast proliferation thiab ECM synthesis, accelerating lub kho ntawm daim tawv nqaij qhov txhab. Piv rau scaffolds tsis sivcardarine ntsiav tshuaj, cov ntaub so ntswg ntawm daim tawv nqaij tom qab siv yog tawv dua thiab cov nti me me.

Inflammatory teb yog ib qho tshwm sim nyob rau hauv cov txheej txheem ntawm kev kho cov ntaub so ntswg, tab sis ntau dhau inflammatory teb tuaj yeem cuam tshuam cov ntaub so ntswg. Tom qab cov ntaub so ntswg puas lawm, lub cev tiv thaiv kab mob sai sai pib cov lus teb inflammatory los tshem tawm cov kab mob thiab cov ntaub so ntswg necrotic ntawm qhov chaw raug mob. Txawm li cas los xij, yog tias cov lus teb inflammatory tshwm sim ntau dhau, nws tuaj yeem ua rau kev tso tawm ntau ntawm cov kab mob inflammatory, uas tuaj yeem ua rau cov kab mob extracellular matrix, inhibit cell proliferation thiab sib txawv, thiab yog li cuam tshuam cov ntaub so ntswg kho.

Ua si los tiv thaiv- cov teebmeem inflammatory hauv cov kab mob sib thooj hauv cov kab mob hauv cov nas, thiab tuaj yeem noj tshuaj raws li inhibit qhov kev nce hauv monocyte chemoattractant protein-1 (MCP-1) mRNA kev qhia tshwm sim los ntawm palmitic acid thiab qog necrosis factor alpha (TNF alpha). MCP-1 yog ib qho tseem ceeb inflammatory chemokine uas tuaj yeem nrhiav cov kab mob tiv thaiv kab mob xws li monocytes mus rau qhov chaw ntawm qhov mob, ua rau muaj kev mob hnyav ntxiv. Los ntawm inhibiting qhov kev qhia ntawm MCP-1, infiltration ntawm inflammatory hlwb raug txo, li no alleviating inflammatory teb.

Qhia nws mus rau hauv cov ntaub so ntswg engineering scaffolds tuaj yeem txo cov lus teb inflammatory tom qab stent implantation thiab txhawb nqa cov ntaub so ntswg du. Piv txwv li, hauv articular pob txha mos engineering, articular pob txha mos yog cov ntaub so ntswg uas muaj peev xwm kho tau tsawg heev. Thaum cov pob txha mos sib koom ua ke raug puas tsuaj, inflammatory tshwm sim sai sai, ua rau kev tuag ntawm chondrocytes thiab degradation ntawm pob txha mos matrix.

Lub scaffold loaded nrog cov khoom tuaj yeem txo qhov mob hauv qhov sib koom ua ke thiab tiv thaiv chondrocytes los ntawm kev puas tsuaj. Cov kev sim tsiaj tau pom tias siv cov load-cov kabmob scaffolds los kho cov pob txha pob txha pob txha sib koom ua ke tuaj yeem txhawb kev loj hlob thiab sib txawv ntawm chondrocytes, ua kom cov synthesis ntawm pob txha mos matrix, thiab txhim kho kev sib koom tes.

Lub microenvironment ntawm cov qog nqaij hlav feem ntau yog acidic, uas yog tshwm sim los ntawm kev loj hlob sai thiab metabolic txawv txav ntawm cov qog hlwb. Tus nqi pH ntawm cov ntaub so ntswg ib txwm yog li 7.4, thaum pH tus nqi ntawm cov qog nqaij hlav tuaj yeem qis li 5.0-6.5. Los ntawm kev siv tus cwj pwm no, pH teb cov neeg nqa tshuaj tuaj yeem tsim los ua kom tiav cov tshuaj tso tawm ntawm qhov chaw qog. Npaj pH rhiab nanoparticles los ntawm copolymerizing GW-501516 nrog polyethylene glycol (PEG) thiab polylactic acid (PLA).

PEG muaj biocompatibility zoo thiab dej solubility, uas tuaj yeem ncua lub sijhawm ncig ntawm nanoparticles hauv cov ntshav; PLA yog cov khoom siv biodegradable polymer feem ntau siv rau hauv kev npaj cov neeg nqa tshuaj.

Nyob rau hauv ib puag ncig physiological ib puag ncig (pH 7.4), cov qauv nanoparticle ruaj khov thiab cov tshuaj tso tawm qeeb. Qhov no yog vim hais tias cov tshuaj bonds nyob rau saum npoo ntawm nanoparticles kuj ruaj khov ntawm ib txwm pH qhov tseem ceeb, thiab cov tshuaj yog encapsulated nyob rau hauv lub nanoparticles, ua rau nws nyuaj rau tso tawm.

Nyob rau hauv acidic microenvironment ntawm cov qog nqaij hlav (pH 5.0-6.5), nanoparticle qauv disintegrates thiab tso loaded tshuaj tiv thaiv kab mob (xws li doxorubicin), ua kom tiav cov hom phiaj kho. Nyob rau hauv acidic tej yam kev mob, tshuaj bonds nyob rau saum npoo ntawm nanoparticles undergo hydrolysis cov tshuaj tiv thaiv, ua rau cov txheej txheem puas thiab tso tshuaj. Cov txheej txheem no tuaj yeem txhim kho kev ua tau zoo ntawm cov tshuaj thaum txo cov kev mob tshwm sim lom ntawm cov ntaub so ntswg. Vim hais tias cov tshuaj feem ntau tso tawm ntawm qhov chaw qog, qhov concentration ntawm cov tshuaj uas ib txwm cov ntaub so ntswg tuaj rau hauv kev sib cuag nrog yog qis dua, yog li txo qhov kev puas tsuaj ntawm cov tshuaj rau lub cev.

Lub teeb teb cov tshuaj muaj peev xwm ua tiav cov tshuaj tso tawm los ntawm lub teeb stimulation. Lub teeb muaj qhov zoo ntawm qhov muaj zog penetrability thiab cov chaw taws teeb tswj, uas tuaj yeem ua tiav cov kev cai ntawm kev tso tshuaj. Muab nws nrog cov tshuaj tua kab mob (xws li porphyrin derivatives) los tsim cov tshuaj tua kab mob photoresponsive. Lub photosensitizer yog ib yam khoom uas tuaj yeem nqus tau lub teeb ntawm ib lub wavelength tshwj xeeb. Tom qab nqus lub teeb lub zog, cov photosensitizer tau hloov pauv hluav taws xob, tsim lub zog.

Nyob rau ze -infrared lub teeb irradiation, cov photosensitizer ua kom sov, ua rau muaj kev hloov pauv hauv cov cab kuj thiab tso cov tshuaj.

Nyob ze lub teeb infrared muaj peev xwm nkag mus rau hauv cov ntaub so ntswg muaj zog thiab tuaj yeem nkag mus tob rau hauv cov ntaub so ntswg ntawm tib neeg lub cev, thaum ua rau cov ntaub so ntswg puas tsawg. Cov txheej txheem no tuaj yeem siv los kho cov kab mob sib sib zog nqus, xws li mob qog noj ntshav lossis mob hlwb. Piv txwv li, txhaj tshuaj nanoparticles loaded nrog nws thiab photosensitizer rau hauv cov qog nqaij hlav tuaj yeem ua tiav cov tshuaj tso tawm hauv zos thiab txhim kho kev kho mob los ntawm ze rau -infrared irradiation. Hauv kev sim tsiaj, siv cov tshuaj tua kab mob photoresponsive los kho mob qog noj ntshav ntawm daim tawv nqaij tuaj yeem cuam tshuam cov qog loj hlob thaum txo kev puas tsuaj rau cov tawv nqaij ib puag ncig.

Nws tseem tuaj yeem siv los tsim cov phiaj xwm xa tshuaj, txhim kho lub hom phiaj thiab bioavailability ntawm cov tshuaj. Lub hom phiaj siv tshuaj xa tuaj tuaj yeem xa cov tshuaj mus rau qhov chaw mob, txo cov kev faib tshuaj thoob plaws hauv lub cev, yog li txhim kho kev siv tshuaj thiab txo cov kev mob tshwm sim. Piv txwv li, hloov nws ntawm qhov chaw ntawm liposomes los tsim cov liposomes ntev. Liposomes yog nanoscale nqa khoom tsim los ntawm phospholipid bilayers, uas muaj biocompatibility zoo thiab hloov kho.

PEGylation hloov kho ntawmcardarine ntsiav tshuajtuaj yeem ua kom ntev lub sijhawm ntawm liposomes hauv cov ntshav.

PEG tuaj yeem tsim cov hydration txheej ntawm cov liposomes, txo cov kev cuam tshuam ntawm liposomes thiab cov proteins hauv cov ntshav, yog li tsis txhob lees paub thiab tshem tawm los ntawm lub cev tiv thaiv kab mob. Nyob rau tib lub sijhawm, nws tseem tuaj yeem khi rau cov receptors tshwj xeeb ntawm cov qog hlwb kom ua tiav cov phiaj xwm xa tawm ntawm cov tshuaj. Cov qog hlwb feem ntau qhia cov receptors tshwj xeeb ntawm lawv qhov chaw, uas tsis tshua muaj tshwm sim ntawm cov xov tooj ntawm tes. Nws tuaj yeem ua lub ligand uas tshwj xeeb khi rau cov receptors ntawm cov qog hlwb, xa cov tshuaj coj los ntawm liposomes mus rau sab hauv ntawm cov qog hlwb.