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Kukula kwa mabala kumapulogalamu nthawi zambiri kumadziwonekera ngati biofilmm, komwe kumasokoneza machiritso ndipo kumavuta kuthetsa. Mavalidwe atsopano asiliva atsopano amati kuthana ndi matenda a bala, koma ma antibilm awo ndi matenda opatsirana pawokha komanso machiritso amachiritsa nthawi zambiri sadziwika. Kugwiritsa ntchito vitro ndi ku Vivol biofilm mitundu ya Staphylococcus Aureus ndi Pseudomonas Ainoginosa, timanena luso la mavalidwe a Ag1 +; AG1 , amene apanga Ag1, ag1 ndi agari3 a Agafilm ndi momwe amachiritsira. Mavalidwe a AG1 + anali ndi zotsatira zochepa pa bala biofilm mu vitro ndi mbewa (C57BL / 6j). Mosiyana ndi izi, oxygenited Ag Mchere ndi Ag1 + / Edta / BC / BC Mavalidwe awa anali ndi zotsatira zoyipa za mabala omwe ali ndi kachilomboka, ndi mavalidwe amchere omwe ali ndi mwayi wopindulitsa kwambiri, kukula kwa bala, komanso kutupa kuyerekeza ndi mankhwala ena a siliva. Zojambula zosiyanasiyana za mavalidwe asiliva zimatha kukhala ndi zovuta zovulaza biofilm ndi machiritso, ndipo izi zikuyenera kuzilingalira posankha kuvala mabala a a biofilm.
Mabala amalonda amafotokozedwa kuti "mabala omwe amalephera kupita patsogolo pazomwe amachiritsa m'njira mwadongosolo komanso panthawi imodzi" 1. Mabala achikulire amapanga zovuta zamaganizidwe, zachuma komanso zachuma kwa odwala ndi dongosolo lazaumoyo. NTHAWI YOPHUNZIRA Pachaka pochizira mabala ndipo zimagwirizana ndi mitengo ya £ 8.3 biliyoni mu 2017-182. Mabala achikulire nawonso ali ndi vuto ku United States, ndi Medicare ikuwonjezera mtengo wa pachaka wothandizira odwala omwe ali ndi mabala a $ 28.1-8 biliyoni3.
Matenda ndi chinthu chachikulu chomwe chimalepheretsa machiritso a bala. Matenda nthawi zambiri amaonekera ngati biofilms, omwe ali mu 78% ya mabala osachirikiza. Fayilo ya biofilm ikakhala yolumikizidwa ndi malo osasinthika, monga mabala am'madzi, ndipo amatha kupanga mawonekedwe owonjezera polymer (eps) - madera. Vuto la biofilm limagwirizanitsidwa ndi kuyankha kowonjezereka komwe kumayambitsa kuwonongeka kwa minofu, komwe kumachepetsa kapena kupewa machiritso4. Kuchuluka kwa kuwonongeka kwa minofu kumatha kuchitika chifukwa chowonjezera ntchito ya Matrix metallophrofinatinases, collagenase, elstase komanso zopangira mpweya wa okosijeni5. Kuphatikiza apo, ma cell otupa ndi ma biofilms okwera okwera ogula ndipo chifukwa chake amatha kuyambitsa minofu yakomweko, maselo okwanira a mpweya wofunikira woyenera kutembenukira minofu yothandiza6.
Kukhwima ma biofilms amalimbana kwambiri ndi othandizira antimicrobial, amafunikira njira zokwiyira kuti azilamulira matenda a biofilm, monga makina amakina omwe amatsatiridwa ndi mankhwala othandiza a antimarobial. Chifukwa ma BOOfilms amatha kusinthasintha, kugwiritsa ntchito ma antimicrobials okwanira amatha kuchepetsa chiopsezo chokonzanso matenda opatsirana.
Siliva imagwiritsidwa ntchito kwambiri m'matavala antimicrobial ndipo nthawi zambiri amagwiritsidwa ntchito ngati chithandizo choyambirira cha mabala omwe ali ndi matenda. Pali mavalidwe ambiri ambiri omwe ali ndi siliva, iliyonse yomwe ili ndi zida za siliva, kuzunzika, ndi base matrix. Kupita patsogolo kwa siliva mabatani achititsa kuti likhale lasiliva watsopano. Mawonekedwe a siliva (AG0) ndiCert; Kuti tikwaniritse mphamvu ya anticrobial, iyenera kutaya elekitironi kupanga siliva inoc (AG1 +). Mavalidwe asiliva okhala ndi siliva kapena siliva yachitsulo yomwe, ikawonetsedwa ndi madzi, kuwola kupanga ma ag1 +. Akesi awa + ag1 + agé + a Aga1 + a Agarteria, amachotsa ma elekitironi kuchokera kuzinthu zamitundu kapena njira zofunika kwambiri kuti adzapulumuke. Tekinoloji yaukadaulo yadzetsa chitukuko cha siliva watsopano, Ag Oxysalts (siliva nitrate, Ag7no11), omwe amaphatikizidwa m'matolidwe a bala. Mosiyana ndi siliva wazachikhalidwe, mchere wa mchere womwe uli ndi mpweya umatulutsa siliva wokhala ndi ma AG1, aga2 + ndi aga3 + ndi aga3. In vitro studies have shown that low concentrations of oxygenated silver salts are more effective than single ion silver (Ag1+) against pathogenic bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli8,9. Mtundu wina watsopano wamavalidwe asiliva umaphatikizaponso zosakaniza zina, ndi Ethylenzensiineacetraocettic acid (edta) ndi benzethonium chloride (BC), kuwonjezeredwa kuti ayang'ane BOfilm Expsmmm. Maukadaulo atsopano asiliva atsopanowa amapereka njira zatsopano zopangira bala. Komabe, zovuta za mankhwala antiberial awa pa bala ndi matenda opatsirana pawokha ndizofunikira kuonetsetsa kuti sapanga chilengedwe chosavomerezeka kapena machiritso. Zokhudza mu vitro siliva Cytotoxicity yanenedwa ndi zovala zingapo zasiliva10,11. Komabe, ku Vitro Cytotoxicity sanamasuliridwe ku Vivo moopsa, ndipo zovala zingapo za Ag1 + zawonetsa mbiri yabwino yachitetezo12.
Apa, tinkafufuza mphamvu ya carboxymethylcelulose mavalidwe omwe ali ndi masiliva a siliva motsutsana ndi bala biofilm mu vitro ndi ku Vivo. Kuphatikiza apo, zotsatira za mavalidwe awa pa mayankho amthupi ndi machiritso popanda matendawo adayesedwa.
Mavalidwe onse omwe amagwiritsidwa ntchito anali opezeka pa malonda. 3M Kerracel gel Able directing (3m, Knutsford, UK) ndi manticticrobial 100% Carboxyllulose Mavalidwe atatu a CMC a Antimicrobial CMC adawunika, ndi 3m Kerracel A A AG AG Mchere wasiliva wa uxya (ag7no11) m'matsenga apamwamba kwambiri (AG1 +, aga2 + ndi ag3 + ndi ag3. Pa kuwonongeka kwa Ag7no11, ag1 +, ag2 + ndi agan3 + ag3 amapangidwa mu chiyerekezo cha 1: 2: 4. A Gaacel Ag Owonjezera Kuvala Zokhala ndi 12% Siliva Chiloride (AG1 +) (Altide) 13 ndi a Edzethonium chloride (Disside, UK) 14.
Zingwe zomwe zimagwiritsidwa ntchito pophunzirayi zinali mphuluginoda Nctc 10781 (Healccury England, SalisbungCus arewas NctCory 6571 (Healcbury England).
Mabakiteriya adabzala usiku wonse mu a Muller-Hinton msuzi (oxid, altrincham, UK). Chikhalidwe Chachisanu ndi Chakudya Cha Usiku ). ) A Colonil Biofilm mapangidwe 37 ° C kwa maola 24. Atsogoleri atsamunda awa adayesedwa chifukwa cha malo ogona.
Dulani kuvala mu 3 masentimita lalikulu ndi chimbudzi chonyowa ndi madzi osabala. Ikani bandeji pamwamba pa beofilm ya korona pa mbale ya Agar. 249 Pambuyo pa maola 24 a makulitsidwe pa 37 ° C, Plate Worte Worte Wokhazikika adachitidwa pa Muller-Hinton Agar mbale. Chithandizo chilichonse ndi nthawi yake chinachitidwa munthawi yochepa, ndipo ndi mbale ya mbale ija idabwerezedwanso chifukwa cha kusamala kulikonse.
Khungu la nkhumba limapezeka kuchokera ku nkhumba zoyera zoyera mkati mwa mphindi 15 zophera malinga ndi makina a ku European Union. Khungu limamedwa ndikutsukidwa ndi zopukuta zakumwa, kenako ndikuzizira ku -80 c kwa maola 24 kuti muchepetse khungu. Pambuyo pakuyenda, zidutswa za khungu 1 zidasambitsidwa katatu ndi PBS, 0,6% sodium hypochlorite, ndi 70% ethanol kwa mphindi 20 nthawi iliyonse. Musanachotse eldermis, chotsani ethanol iliyonse yotsalira posamba katatu m'malo osabala Pbs. Khungu limakhala loyatsidwa mumbale 6 ndi μm-millipore (Merck-Millipore) pamwamba ndi millipore) Mphungu. Sing'anga (ya DullecCo's Albecforted Spanter - Aldrich Ltd.).
A Colonial Biofilms anali wamkulu monga momwe afotokozedwera kafukufuku wa biofilm. Nditayamba kuyerekezera baofilm pa nembanemba kwa maola 72, beofilm idagwiritsidwa ntchito pakhungu pogwiritsa ntchito chisa chosatsutsika chotupa ndipo nembanemba idachotsedwa. The Broofilm inali yokhazikika padenga la nkhumba kwa maola 24 owonjezera pa 37 ° C kuti alolebe kukhwima ndikutsatira khungu la nkhumba. A FOfilm anali atakhwima ndikuvala, kuvala ka 1.5 masentimita, ophimbidwa ndi nthawi yophulika ndi madzi osabala, kunagwiritsidwa ntchito mwachindunji pakhungu ndikuwumba pa 37 g kwa maola 24. Mabakiteriya okwanira adayang'aniridwa ndi kukhazikika pogwiritsa ntchito prestobluclute cellubility (kutumizidwa, matekinoloje, paisley, UK padziko lonse pofotokoza za mphindi 5. Gwiritsani ntchito kamera ya Leica DFC425 ya digito kuti ichitike zithunzi za Leica mz8. Madera achikuda a pinki adachulukana pogwiritsa ntchito Pro Pro Propurani Mapulogalamu 10 (ma cyberneneticncn inc, rodville, Md Chithunzi-Pro-Progracy)). Scanning ma microkycopy adachitidwa monga tafotokozera pansipa.
Mabakiteriya omwe anakula usiku wonse anaphwanyidwa 1: 100 mwa mwezi wa mueller-Hinton. 200 μL ya Chikhalidwe idawonjezeredwa ku chosabala 0,2 μm whayman cyclokore membrane (wa Kaidstone, UK) ndikuyika pa Muller-Hinton Agar. Mbale mbale za biofilm zinali zokutira pa 37 ° C kwa maola 72 kuti ilole mapangidwe a biofilm a biofilm.
Pambuyo pa masiku atatu a zinthu zosasinthika, bandeji ya 3 CM2 idayikidwa mwachindunji pa biofilm ndi sevitated 37 ° C kwa maola 24. Pambuyo pochotsa bandeji kuchokera pamtunda wa biofilm, 1 ml ya prestoblue cell vagent (yatchrogen, Waltham, ma) adawonjezeredwa pamtunda wa biofilm iliyonse. Maonekedwe adawuma pamaso pa mitundu ya utoto adajambulidwa pogwiritsa ntchito kamera ya Nikon D2300 digito (Nikon UK Ltd., Kingston, UK).
Konzani zikhalidwe za usiku pa Mueller-Hinton Agar, kusunthira madera 10 ml mueller-Hinton msuzi ndikusinthana pa 37 ° C (100 RPM). Pambuyo pausiku, chikhalidwe chidachepa 1: 100 mu The Muller-Hintun Both ndi 300 μl Cyclopene membrane (Whamman Cyclopore Membrane (Whammani International Cyclopene) . . Wokhwima bifilm adayikidwa pachilonda chomwe chafotokozedwa pansipa.
Ntchito zonse ndi nyama zomwe zimachitika ku University of Manchester pansi pa layisensi yovomerezedwa ndi ofesi ya zidole (P8721BD27) komanso mogwirizana ndi Asamudwe anyumba yomwe ili pansi pa 2012 yomwe idasindikizidwa. Olemba onse adatsatira malangizo omwe afika. Ma mbewa asanu ndi atatu a C57BL / 6j (Envigo, oxona, UK) adagwiritsidwa ntchito kwa onse mu maphunziro a Vivo. Makoswe anali ndi vuto la Isoflura (Piramial Mowa, Lost Drayton, UK) ndi malo awo opumira adametedwa ndikutsukidwa. Kenako mbewa iliyonse inali itaperekedwa 2 × 6 mm kachilombo ka Humaidel Biopsy Putchy (Schuc International, Hertfordshire, UK). Kwa mabala omwe ali ndi kachilomboka, gwiritsani ntchito maofesi a maola 72 Gawo limodzi la masentimita imodzi la kuvala limaphimbidwa ndi madzi osasunthika kuti asunge malo onyowa. Mavalidwe adagwiritsidwa ntchito mwachindunji pachilonda chilichonse ndikukuta ndi 3m tegaderm filimu (3m, Bracknell, UK Buprenorphine (nyama, York, UK) idaperekedwa kwa kukhazikika kwa 0,1 mg / kg ngati analgesic. Moice mbewa pakatha kuvulala pogwiritsa ntchito dongosolo 1 njira ndikuchotsa, hael, ndikusunga bala kuti isakhale.
Hematoxylin (thermofas sayansi) ndi esin (thermofaur sayansi) Chiwopsezo chidachitika malinga ndi protocol ya wopanga. Dera la bala ndi ku Reeeliation adachulukanso pogwiritsa ntchito Pro Pro Propurani:
Magawo a minod adazengereza ku Xylene (thermofaur pa IK Immunohistochemist idachitika pogwiritsa ntchito vectostain Elite Elc PK-6104 Kit (Vector Laboratories, Burtename, Cold Protocol wa Opanga. Ma antibowees oyamba ku neutrophils nimp-r14 (thermofaul sayansi) ndi macolages a CD107B, UK, UK, UK ABC ndi Vector Nova Red Peroxidase (HRP) Gawo la Kit (Vector Laboratories, Burmamees, Burmame, Ca) ndi Coversenstan ndi Heatotoxylin. Zithunzi zidapezeka pogwiritsa ntchito Olympus BX43 Microscope ya Digisk ndi Olympus DP73 Digital (OlympheS, Southend-Southend-pa-nyanja, UK).
Zitsanzo za pakhungu zinali zokhazikika mu 2,5% glutaraldehyde ndi 4% formaldehyde mu 0.1 m hepes (Ph 7.4) kwa maola 24 pa 4 ° C Grours c. Zitsanzozo zidasiyidwa pogwiritsa ntchito ethanol ndikuwuma mu co2 pogwiritsa ntchito chowuma cha quorum (quorum, uk) ndi sluredium slurom slurom / blow. Malingaliro adaganiza zogwiritsa ntchito ma microscope 250 a Interrancrope (Thermofaus asayansi) kuti awoneni pachiwopsezo cha bala.
Toto-1 iodide (2 μm) idagwiritsidwa ntchito pa bala ndi mabhonge nyemba zokhala ndi 5 min 37 ° C (thermofaur sayansi ya 37 (10) (10) Zithunzi za mphindi 15 zifa zinkapangidwa pogwiritsa ntchito leica TC SP8.
Zambiri zofananira komanso zamaukadaulo zidapangidwa ndikusanthula pogwiritsa ntchito graphpad prism v9 (graphpad pulogalamu, LA Jolla, Ca). Kusanthula kwa njira imodzi yosiyanasiyana pogwiritsa ntchito mayeso a Hoc Sypnet adagwiritsidwa ntchito kuyesa kusiyana pakati pa chithandizo chilichonse komanso kuvala kosavomerezeka. Mtengo wa P <0.05 udawoneka wofunika.
Ubwino wa siliva Gel gelsemes a geofil amayesedwa motsutsana ndi madera a Staphylococcus areus ndi pseudomonos aeruginosa ku vitro. Mavalidwe asiliva ali ndi njira zosiyanasiyana zasiliva: mavalidwe asiliva achikhalidwe amapanga ma AG1 +; Mavalidwe asiliva, omwe amatha kupanga ag1 + ion itatha kuwonjezera mabakitsiriya ndikuwonetsa mabakiteriya okhala ndi antibacteria. Maini15 ndi mavalidwe okhala ndi mchere wa aga wampweya womwe umatulutsa AG1 +, ag2 ndi a AG3 + a AG3. Kuchita bwino kwake kudayerekezedwa ndi kuvala kosagwirizana ndi kontimicrobi yaying'ono komwe kumapangidwa kuchokera ku ulusi wopangidwa. Mabakiteriya okwanira mkati mwa ma biofilm adawunika maola 24 aliwonse kwa masiku 8 (Chithunzi 1). Patsiku la 5, beofilm lidatsitsimuka ndi 3.85 × 105s. Staphylococcus Aureus kapena 1.22 × 105p. Aeruginosa kuwunika kuchira kwachinyengo. Poyerekeza ndi mavalidwe osavomerezeka a Ag1 + ag1 anali ndi mphamvu zochepa pa bakiteriya mu Staphylococcus Aureus ndi Pseudomonas Aeruginosa Biofilms masiku 5. Mosiyana ndi izi, mavalidwe okhala ndi oxygenated ag ndi ag1 + edta / BC anali othandiza pakupha mabakiteriya mkati mwa masiku 5. Pambuyo pa kubwerezedwa kubwerezedwanso ndi mabakiteriya a planktonic pa tsiku 5, palibe kubwezeretsa kwa biofilm komwe kumawonedwa (mkuyu.).
Kuchuluka kwa mabakiteriya okwanira mu Staphylococcus aureus ndi pseudomonos aeruginosa biofilms pambuyo pa chithandizo ndi mavalidwe asiliva. Madera a zinthu za Staphylococcus a Aureus ndi Pseudomonos Aeruginosa adathandizidwa ndi mavalidwe a siliva kapena ma bacteria oletsa, ndipo kuchuluka kwa mabakiteriya okwanira adatsimikiza maola 24 aliwonse. Pambuyo pa masiku 5, biofilm idatsitsimuka ndi 3.85 × 105s. Staphylococcus Aureus kapena 1.22 × 105p. Korona wa bacterioplaopton pseudomonas aeruginosa adapangana payekha kuti ayesere kuchira. Zojambula zimawonetsa kutanthauza +/- cholakwitsa.
Kuwona m'maganizo a mavalidwe asiliva pa incorm ya bifilmm, mavalidwe ankayikidwa kuti akhwime a biofilms okhwima pakhungu la Ex Vivo. Pambuyo pa maola 24, kuvala kumachotsedwa ndipo ma biofilm amakhazikika ndi utoto wabuluu wabuluu, womwe umapangidwa ndi mabakiteriya okhala ndi pinki. FAOfilms omwe amathandizidwa ndi mavalidwe owongolera anali pinki, kuwonetsa kukhalapo kwa mabakiteriya othandiza mkati mwa fifilm (Chithunzi 2A). Mosiyana ndi zimenezo, za biofilm yomwe imachitidwa ndi kuvala kwa okuni okunja inali makamaka yabuluu, yomwe ikuwonetsa kuti mabakiteriya omwe ali pamwamba pakhungu la nkhumbayo anali ndi mabakiteriya (Chithunzi 2b). Kuphatikizika kwa buluu ndi zapinki kunawonedwa ndi ma biofilms omwe ag1 + zosakanikirana, zomwe zikuwonetsa kukhalapo kwa mabakiteriya othandiza komanso osavomerezeka. Madera osonyeza zomwe sizikhudzidwa ndi kuvala kwasiliva (Chithunzi 2d). Kuchuluka kwa ntchito (pinki) ndi madera osagwira ntchito omwe adawonetsa kuti chigamba chowongolera chinali 75% yogwira (Chithunzi 2e). Ag1 edta / BC amavala bwino kwambiri kwa mavalidwe amchere a Ag. Kuvala kwa Ag1 + kuchepetsedwa kumabakiteriya kudzera 21%. Izi zida zimawonedwa ndikugwiritsa ntchito Scanning ma microctopy (Sem). Pambuyo pa mankhwala ovala ndi kuvala kwa Ag1 Minyewa ya collagen imatha kuonedwa ngati mawonekedwe a khungu la porcine (Chithunzi 2G). Pambuyo pa chithandizo ndi agta / BC kuvala, mabakiteriya komanso malo osungirako nyama okhala ndi collagen anali owoneka (Chithunzi 2I).
Kuwona kwa Pseudomonas Ainoginosa bifilm pambuyo mankhwala kuvala siliva atavala siliva. . Mabakiteriya okhala ndi moyo ndi mabakiteriya, osakwanira apiteriya komanso khungu la nkhumba ndi lamtambo. . Sem Scale Bar = 5 μm. .
Kuti mudziwe ngati kulumikizana kwambiri pakati pa mavalidwe ndi ma biofilmmmmmm omwe amakhudza luso la mavalidwewo, mabilogalamu a colononbomems oyikidwa pathyathyathya adathandizidwa ndi mavalidwe kwa maola 24 kenako ndikukhazikika ndi utoto wogwira. The sanati yopanda tanthauzo linali lofiirira mu utoto (Chithunzi 2j). Mosiyana ndi ma biofilms omwe amathandizidwa ndi mavalidwe okhala ndi masamba agalasi (Chithunzi 2K), ma biofilms omwe amathandizidwa ndi mavalidwe okhala ndi ag1 + kapena Ag1 + Ed, M). Kukongoletsa kwapamwamba kumeneku kukuwonetsa kukhalapo kwa mabakiteriya othandiza ndipo kumalumikizidwa ndi malo osavomerezeka mkati mwa kuvala. Madera omwe amapanga malo omwe amapanga malo omwe amafa omwe amalola mabakiteriya mkati mwa Theofilm kuti akhale ndi moyo.
Kuti mudziwe luso la mavalidwe a siliva ku Vivo, makulidwe odzaza ndi mabala a mbewa s. Aureus ndi P. Airuginosa biofilms amathandizidwa ndi mavalidwe asiliva. Pambuyo pa masiku atatu chithandizo, kuwunika kwa macroscopic kunawonetsa kuti bala laling'ono likagwiridwa ndi mavalidwe amchere otumphuka poyerekeza ndi mavalidwe osagwirizana ndi antimicrobial (Chithunzi 3A). Kutsimikizira izi, mabala adakololedwa ndi bala ndi ma balani okwanira pa hematoxylin ndi eosin-stopment zigawo za Pro Pro Proder 10 (Chithunzi 3I-l).
Mphamvu ya mavalidwe a siliva pa bala la bala ndi esithelizilization wa mabala omwe ali ndi kachilombo ka biofilms. (A-H) maselo ang'onoang'ono omwe ali ndi ma biofilmonas aerugunosa (a-d) ndi ma staphyloccus areus (E-h) Arurus (E-h) Alurus (E-h) mankhwala osasamala a Ag1 +, ag1 + kuvala. Oyimilira macroscopic. Mabala a mbewa ndi AG1 + EDTA / BC diresi. . Kuchulukitsa kwa ma bala (m, o) ndi peresenti reeeeliation (N Zojambula zimawonetsa kutanthauza +/- cholakwitsa. * amatanthauza p = <0.05 ** amatanthauza p = <0.01; Macroscopic scale = 2,5 mm, kukula kwa mbiri = 500 m.
Kuchuluka kwa malo ovulala mu mabala omwe ali ndi pseudomonas aerugulA brofilm Zowona. kufika poizoni (Chithunzi 3m). P = 0.423). Mabala omwe amathandizidwa ndi ag1 + kapena ag1 + ed Chithandizo cha mankhwala ophika mchere ag amchere amalimbikitsanso kukonzanso kokulirapo kuposa kuvala kosagwirizana ndi mantiminiti (p = 0.029) ndi aga1 Chithunzi 3N). . , motero).
Makonda ofanana ndi zilonda ndi epithelial Regeanetion adawonedwa m'mabala omwe ali ndi s. Aureus biofilms (Chithunzi 3o). Zovala zomwe zimakhala ndi mchere wambiri wamalonda (2.0 mm2) ndi 23% poyerekeza ndi kuwongolera komwe sikunachitike (2.5 mm2), 0,304) (mkuyu.). Kuphatikiza apo, malo ochiritsira odwala ku Ag1 + omwe adachepetsedwa pang'ono (2,4 mm2), pomwe bala limathandizidwa ndi Ag1 + Edta / BC sanachepetse malo ovulala (2.9 mm2). Mchere wa oxygen amalimbikitsanso kukonzanso mabala omwe ali ndi matenda a S. Ga1 + kapena kuvala, p = 0.903) ndi Ag + 1 EdTA / BC Drating (14%, p = 0.965) yosonyeza kuwongolera.
Kuwona momwe mavalidwe asiliva ali pa intaneti, Toto 1 ndi Sypo 60 inoodide kuchitidwa (mkuyu. 4). Toto 1 Iodides ndi utoto wopanda ungwiro womwe ungagwiritsidwe ntchito kuwonetsera molondola ma acid a nuclecellular enspor, omwe amakhala ambiri m'mawu a biofilms. Syto 60 ndi utoto wokhazikika wa cell wogwiritsidwa ntchito ngati wovuta16. Zowona za Toto 1 ndi Syto 60 inoodide otayika ndi ma biofilms a pseudolnosa (Chithunzi 4alosaccUs (Chithunzi 4a-l) Kuchepetsa kwa masiku atatu kuchepetsedwa. okhala ndi mchere wa okosijeni a AG ndi AG1 + Edta / BC. Ag1 + popanda ma antibilm owonjezera omwe amachepetsa mabala am'manja omwe ali ndi mabala am'manja omwe ali ndi pseudoninonas aerugunosa koma sanali othandiza mabala a Staphylococcus.
Mu vivo akuganiza za bala biofilm pambuyo pa masiku atatu chithandizo chowongolera kapena mavalidwe asiliva. Zithunzi zosokoneza bongo za pseudomonas aeruginosa (a-d) ndi staphylococcus areus (i-l) yokhazikika ndi zowonjezera 1 (zobiriwira) kuti ziwonekere ma acid erefilmm a soofilm. Kukhazikika ma entracellular nucracles, gwiritsani ntchito Sypo 60 (Red). acid. P. Scanning magetsi mabala omwe ali ndi matenda a pseudomonosa (E-h) ndi staphylococcus rufils (M-p) biofilms pambuyo pa mankhwala omwe amawongolera ndi mavalidwe asiliva. Sem Scale Bar = 5 μm. Kuyerekeza kwa mawonekedwe a Scale Bar = 50 μm.
Kusanthula ma microcycycopy kunawonetsa kuti mbewa zopangidwa ndi madera a ma biofilm a pseudolnosa (Chithunzi 4e-h) anali ndi mabala ochepa omwe ali ndi mavalidwe onse atatu.
Kuti mudziwe za mavalidwe a siliva pa kutupa kwa baofilm - zigawo za mabala omwe ali ndi vuto la biofilm omwe amathandizidwa ndi mabatani atatu a Immunohistrance dongo la neutrophils ndi macrophils. Kutsimikiza kwa neutrophils ndi macolashoges mkati. minofu ya granula. Chithunzi 5). Mavalidwe onse a siliva adachepetsa kuchuluka kwa neutrophils ndi macolages mu mabala omwe ali ndi matenda a pseudoninos Aitroginosa amayerekezedwa ndi mavalidwe osavomerezeka masiku atatu. Komabe, chithandizo chokhala ndi zovala zamchere zama siliva zam'madzi zomwe zimapangitsa kuti muchepetse kwambiri mu neutrophils (p = <0.0001) ndi macolages (P = <0.0001) Kuyerekeza ndi mavalidwe ena asiliva Ngakhale AG1 + Edta / BC adalimbikitsa bala biofulm, idachepetsa kuchuluka kwa neutrophil ndi macophir mpaka pang'ono kuposa kuvala kwa Ag1. Mabala ochepera omwe ali ndi s. Aureus Biofilm adawonedwanso atavala ndi Ag (p = <0.0001) ndi ag1 edta / 0.0043) oxisols poyerekeza ndi kuwongolera. Zomwezi zimachitika chifukwa cha Neutropenia. bandeji (mkuyu. 5k). Komabe, kuvala kwamchere kwa aga kwamchere kokha komwe kunawonetsa kuchepa kwakukulu kwa macrophages mu granation minofu yoyerekeza ndi ma alavu omwe ali ndi matenda a S. AUREUS) (Chithunzi 5l).
Neutrophils ndi macropheges adachulukana m'mabala omwe ali ndi matenda a pseudolnosa ndi staphylococcus aerus. Neuutrophils (AD) ndi macrophages (eh) adakhazikika m'magawo a minofu yokhazikika ndi ma antibodies omwe ali pa neutrophils kapena macropheges. Kuchuluka kwa neutrophils (i ndi k) ndi macrophages (j ndi l) m'mabala omwe ali ndi matenda a pseudolnosa (i ndi j) areulms (k & l) biofilms. N = 12 pagulu lililonse. Zojambula zimawonetsa kutanthauza +/- Vuto Lokhazikika, kufunikira kwa ma antibacterial kuvale, * kumatanthauza p = <0.05, ** amatanthauza p = <0.01; *** amatanthauza p = <0.001; chikuwonetsa p = <0.0001).
Kenako tidawunikiranso mphamvu za mavalidwe asiliva pa matenda opachira. Mabala omwe siali ogwiritsa ntchito omwe alibe matenda amathandizidwa kuvala kapena kuvala kwasiliva kapena kuvala siliva kwa masiku atatu (Chithunzi 6). Pakati pa mavalidwe a siliva amayesedwa, mabala okhawo omwe amathandizidwa ndi mafuta amchere otumphuka amawoneka kocheperako pazithunzi zama macroscopic kuposa mabala (Chithunzi 6A-d). Kuchuluka kwa malo ogulitsira bala . 6i). Mosiyana ndi izi, palibe kuleka kwa malo ovulala pambuyo pa chithandizo ndi ag1 + (3.38 mm2, p = 0.757) kapena ag1 + 3,054, p = 0,054) poyerekeza ndi gulu lowongolera. Kuchulukitsa epithelial regeneration kunawonedwa ndi kuvala kwa oxysol poyerekeza ndi gulu la oyang'anira (30% vs. 22%, ngakhale izi sizinafike pofotokoza (P = 0,067), zimatsimikizira zotsatira zam'mbuyomu. Kuvala ndi oxylos kumalimbikitsansonso epithelialition. -Efalizetion wa mabala otetezeka17. Mosiyana ndi zimenezo, chithandizo ndi ag1 + kapena ag1 + edta / BC sanalinso mphamvu kapena kuwonetsa kutsika kwa epithelialization kuyerekeza ndi kuwongolera.
Mphamvu ya kuvala bala ya siliva pa bala kumachiritsa mbewa zokhala ndi zosemphana ndi zomwe zili ndi thupi lathunthu. . (Eh) Zoyimira mabala a mabala omwe amakhazikika ndi hematoxylin ndi esin. Kuchulukitsa kwa ma bala (i) ndi peresenti ya remeelialization (j) adawerengedwa kuchokera ku zigawo zakale Zojambula zimawonetsa kutanthauza +/- cholakwitsa. * amatanthauza p = <0.05.
Siliva ali ndi mbiri yakale yogwiritsa ntchito mankhwala osokoneza bongo amachiritso mabala, koma njira zambiri zosiyanasiyana komanso njira zoperekera zimapangitsa kusiyana kwa antimicrobial, 18. Kuphatikiza apo, ma antibilm katundu wa Scorcial Systems Systems samveka bwino. Ngakhale kuti chitetezo chamthupi chimathandizanso ku mabakiteriya a plankktonic, nthawi zambiri amalimbana ndi bifilms19. Mabakiteriya a planktonic amapezeka kawirikawiri ndi Macrophalm, koma mkati mwa ma biofilms, ma cell okalamba amakumananso ndi vuto lomwe limapangitsa kuti ma cell atseke ma cell avopa kuti athetse Mbiri Yachitetezo. Zawonedwa kuti leukocytes ena ena amatha kulowa ma biofilms21 koma kulephera ku mabakiteriya a Gaocytose akamakatetezera ichi chitetezo chikasokonekera22. Njira yotetezerayi iyenera kugwiritsidwa ntchito pothandizira kuteteza chitetezo chamthupi motsutsana ndi matenda a biofilm biofilm. Kuwonongeka kwa zilonda kumatha kusokoneza biofilm ndikuchotsa biofirden ambiri, koma chitetezo chathanzi chimatha kukhala chosathandiza chotsalira Chifukwa chake, mankhwala otsutsa antimicrobies monga mavalidwe asiliva amatha kuthandizira kuyankha kwamphamvu kwa mthupi ndikuchotsa matenda a biofilm. Chifukwa, kuzunzika, kusungunuka, ndi gawo lotumiza lingakhale ndi mphamvu ya siliva. M'zaka zaposachedwa, kupita patsogolo kwaukadaulo wasiliva kwapangitsa kuti zovalazi ziwonjezeke. Monga ukadaulo wamatekinoloje, ndikofunikira kumvetsetsa bwino luso la mavalidwe awa powongolera matenda a bala ndipo, koposa zonse, zomwe zimakhudza siliva zasiliva zamitundu yolima ndi kuchiritsa.
Mu kafukufukuyu, tinayerekezera luso la zovala ziwiri zapamwamba ndi zovala zasiliva zomwe zimapanga ma ag1 + otsutsana ndi ma biofilms pogwiritsa ntchito mitundu ya vivo. Tinamusinthanso mphamvu za mavalidwe awa pa malo a bala ndi matenda odziyimira pawokha. Kuti muchepetse mphamvu ya matrix operekera matrix, mavalidwe onse onse a siliva omwe adayesedwa adapangidwa ndi Carboxymethylceloulose.
Kuonekera kwathu koyambirira kwa mavalidwe a siliva asatchulidwe a pseudomonosa ndi mabatani a Ag1 Masiku angapo. Kuphatikiza apo, mavalidwe awa amalepheretsa kukonzanso bifilm pakuwonekera kwa mabakiteriya a planktonic. Kuvala zovala za Ag1 ndi agloride, imodzi ya siliva ndi matrix monga ag1 + edta / BC, ndipo adachepetsa mphamvu ya bakiteriya mkati mwa nthawi yomweyo. Kuwona kuti chovala cha AG1 + BC chinali chothandiza kwambiri kuvala zovala za Ag1 kwina konse. Zotsatira izi zikuthandizira lingaliro loti BC ndi Edta limakhalanso gawo lina likuthandizira kuvala bwino komanso kuti kusowa kwa chinthu ichi mu kuvala kwamphamvu ku Viro. Tinapeza mavalidwe amchere amtundu wa ag2 + ndi Ag3 + ndipo anali ndi mphamvu zotheka kuposa Ag1 + ndipo anali ofanana ndi AG1 + Edta / BC. Komabe, chifukwa cha kuthekera kwakukulu, ndikosadziwika kuti ndikosakaza mpaka liti ndikugwira ntchito motsutsana ndi bala bloofilmm chifukwa chake muyenera kuphunziranso. Kuphatikiza apo, pali mavalidwe osiyanasiyana osiyanasiyana omwe amapanga ma al1 + omwe sanayesedwe mu phunziroli. Mavalidwe awa amapangidwa ndi ma siliva osiyanasiyana, ozungulira, ndi matrics, omwe angalimbikitse kutumiza kwa a AG1 + komanso luso lawo motsutsana ndi ma biofilms. Ndikofunikanso kudziwa kuti pali ambiri osiyana mu vitro komanso amitundu vivo ankakonda kuwunika zovala za baofilm motsutsana ndi biofilms. Mtundu wa mtundu womwe umagwiritsidwa ntchito, komanso mchere komanso mapuloteni okhutira ndi ofalitsa nkhani omwe amagwiritsidwa ntchito m'mitundu imeneyi, amathandizira kugwirira ntchito kavalidwe. Mu mtundu wathu wa Vivo, tidalola kukhwima ku vitro kenako ndikusamukira kumadoko. Kuyankha kwanyumbayo kumathandiza kwambiri mabakiteriya a plankttonic omwe amagwiritsidwa ntchito pachilondacho, potero amapanga baofilm monga mabala amachiritsa. Kuphatikiza kwa okhwima brofilm kumathandizanso kuyendetsa bwino kwa chizolowezi chachuma cha biofilm polola okhwima a biofilm kuti adzipangitse azofilm azokha kuti adzipangitse. Chifukwa chake, mtundu wathu umatithandizanso kuona luso la mavalidwe a antimicrobial pa quofilms pamaso pa amayamba kuchiritsa.
Tinaonanso kuti kuvala bwino kwa mavalidwe asiliva ku Vitro-Graofilms biofilms ndi khungu la porcine. Kulumikizana kwambiri ndi bala kumawonedwa ngati kovuta chifukwa cha luso la mavalidwe a kavalidwe ka mavalidwe24,25. Zovala zomwe zimakhala ndi mchere wa aga wotuwa zimalumikizana kwambiri ndi ma biofilms okhwima, omwe amapangitsa kuti bakiri la biofilm wogwiritsidwa ntchito pambuyo pa maola 24. Mosiyana ndi izi, atathandizidwa ndi AG1 ndi Ag1 + EDTA / BC, kuchuluka kwakukulu kwa mabakiteriya othandiza omwe adatsalira. Zovala izi zimakhala ndi zotupa kutalika kwa kavalidwe kameneka, komwe kumapangitsa kuti malo ofa omwe amalepheretse kulumikizana ndi beofilm. Mu timicare yathu ya vitro, madera osagwirizana ndi omwe sanagwirizane ndi mabakiteriya okwanira mkati mwa biofilm. Tidayesa kusokonekera kwa bakiteriya pokhapokha maola 24. Popita nthawi, pamene kuvala kumakhala bwino kwambiri, pakhoza kukhala malo ocheperako, kuchepetsa mabakiteriya omwe ali ndi bacteria. Komabe, izi zikuwonetsa kufunikira kwa kapangidwe ka kavalidwe, osati mtundu wa siliva wovala.
Ngakhale mu maphunziro a vitro ndizothandiza poyerekeza zabwino zamitundu yosiyanasiyana, ndikofunikiranso kumvetsetsa zotsatira za ma afoofilms mu vivolms ndi minofu yothandizira kuvala kwa mavafilms. Mphamvu ya mavalidwe a biofilms imawonedwa pogwiritsa ntchito scanning ma microctopy ndi eps exropy ndi eps kukhazikika kwa biofilm pogwiritsa ntchito utoto wa DNA. Tinapeza kuti atatha masiku atatu chithandizo, mavalidwe onse anali othandiza kuchepetsa mabala omasuka kwa maselo, koma kuvala kwa Ag1 + sikunali kothandiza kwenikweni ku mabala omwe ali ndi vuto la Stapyloccus. Kusanthula ma microscopyctrocycycopy adawonetsanso kuti mabakiteriya omwe amapezeka ndi ma batini a siliva, ngakhale atavala zovala zamcherezo, + Edta / BC. Izi zikuwonetsa kuti mavalidwe a siliva omwe amayesedwa anali ndi mawonekedwe osiyanasiyana a biofilm, koma palibe chilichonse mwa mavafilm a Brofilm, ndikuthandizira kufunika kwa chilonda cha matenda a biofilm a biofilm matenda; kugwiritsa ntchito siliva. Chithandizocho chimayambitsidwa ndi kuchepetsa thupi kuti muchotse zambiri za bifilm.
Mabala amalonda nthawi zambiri amakhala otupa kwambiri, ndi ma cell otupa ochulukirapo omwe amakhalapo munthawi yayitali, ndikuwononga kuwonongeka kwa minofu ndikuchotsa mpweya kumafunikira kagayidwe koyenera ndikugwira ntchito mu bala. FAOfilmm imachulukitsa nyumba ya bao la bao la balaji mwa kuchiritsa m'njira zosiyanasiyana, kuphatikizapo zoletsa kuchuluka kwa cell komanso kusamuka ndi kutsegula kwa CytokinemMinem27. Mavalidwe a siliva atakhala othandiza kwambiri, ndikofunikira kumvetsetsa momwe aliri ndi chipatala cha chipatala ndi kuchiritsa.
Chosangalatsa ndichakuti, ngakhale mavalidwe onse a siliva omwe amakhudzidwa ndi mawonekedwe amchere amchere, ongovala mafuta amchere amasiliva owonjezeredwanso mabala omwe ali ndi kachilomboka. Izi zimathandizira zomwe tapeza kale17 ndi a kalan et al. .
Phunziro lathu lapano likufotokoza kusiyana kwaukadaulo wasiliva pakati pa zovala za siliva pakati paukadaulo wa ternology padera la zilonda ndi matenda osokoneza bongo. Komabe, izi zimasiyana m'maphunziro a m'mbuyomu omwe ag1 + Edta / BC adawongolera magawo a machiritso ovulala ku Vivo. Komabe, izi zitha kuchitika chifukwa cha kusiyana kwa zinyama, nthawi yoyeza, ndi njira ya bakiteriya29. Pankhaniyi, miyeso yamalonda idatengedwa masiku 12 nditavulala kuti ilole zodulira zovomerezeka kuti zichitike panyengo ya biofilm nthawi yayitali. Izi zimathandizidwa ndi kafukufuku yemwe adawonetsa kuti zilonda zam'mimba zomwe zimachitidwa ndi zilonda zam'mimba zomwe zimachitidwa ndi AG1 + Edta kugwiritsa ntchito osakhala antimicrobials. mankhwala. Mavalidwe a CMC kuti muchepetse kukula kwa zilonda zam'mimba30.
Mafomu ena ndi ozungulira a siliva omwe adawonetsedwa kale kuti ndi cytotoxic mu vitro 11, koma awa a Vitro, koma awa a Vitro zotsatira sizimatanthauzira nthawi zonse ku Vivo. Kuphatikiza apo, kupita patsogolo kwaukadaulo wasiliva komanso kumvetsetsa kwabwino kwa mitundu yasiliva ndi kuvala zovala zadzetsa mavalidwe ambiri otetezeka komanso othandiza. Komabe, monga ukadaulo wa ukadaulo wa siliva kupita patsogolo, ndikofunikira kumvetsetsa momwe mavalidwe awa pachigoli chaola chaola chaola chaola chaola chala chaola chaola cha nyumba ya chilonda cha nyumba ya chilonda cha nyumba ya chilonda31,32,33. Mudanenedwa kale kuti kuchuluka kwa kuchuluka kwa Epitheliliation kumafanana ndi kuchuluka kwa anti-incupmager M2 macrotype poyerekeza. Izi zidadziwika mumtundu wa mbewa yam'mbuyo pomwe mavalidwe a siliva a Hydrogel basbors adafanizidwa ndi sulfadiazine komanso osakhala antimicrobial hydrogel34.
Mabala okonda amatha kuwonetsa kuti kupezeka kwa neutrophils kumatha kuwononga machiritso35. Pakufufuza mu mbewa ya neutrophil, kukhalapo kwa neutrophils kudachedwa kulocha. Kukhalapo kwa neutrophils owonjezera kumabweretsa mapuloteni ambiri ndi mitundu yambiri ya okosijeni, monga superoxide ndi hydrogen peroxide, yomwe imalumikizidwa ndi mabala osachedwa komanso ochiritsa pang'onopang'ono. Momwemonso, kuwonjezeka kwa manambala a Macophagege, ngati osalamulirika, kumatha kuchititsa kuti achedwe alambe39. Kukwera kumeneku ndikofunikira kwambiri ngati macrophages sangathe kusintha kuchokera ku pronoty pro-prounidype pro -chi kochiritsa, zomwe zimapangitsa kuti ziphuphu zitheke kutulutsa gawo lachiwonetsero cha machiritso. Tidaona kuchepa kwa mapiritsi a neutrophils ndi ma mabala omwe ali ndi vuto la biofilm pambuyo pa masiku atatu othandizira ndi mavalidwe asiliva, koma kuchepa kwapezekanso ndi mavalidwe amchere amchere. Kutsika kumeneku kumachitika chifukwa chaching'ono cha mthupi la chitetezo cha siliva, kuyankha kutsika kwa Bioburden, kapena chilonda chomwe chimakhala mu gawo lamtsogolo pambuyo pake ndipo chifukwa chake ma cur am'mundi mu bala mu bala akuwonongeka. Kuchepetsa kuchuluka kwa maselo okumwa mulondawo kumatha kukhalabe ndi malo oyenera kuchiritsa. Limagwirira ntchito momwe aga amalimbikitsira matenda odziimira pawokha, koma luso la okonda kubereka mpweya, koma mkhalapakati wa ma hydrogen peroxir, angafotokozere izi ndipo amafunikira Phunziro lina lililonse.
Makansa osachiritsira mabala omwe ali ndi kachilomboka amapanga vuto kwa madotolo ndi odwala. Ngakhale mavalidwe ambiri omwe amakhudzidwa ndi mphamvu ya anticticrobial, kafukufuku yemwe samangoyang'ana pazinthu zina zazikulu zomwe zimapangitsa kuti zilonda ziwiri. Kafukufukuyu akuwonetsa kuti maluso asiliva osiyanasiyana ali ndi tanthauzo la mankhwala osiyanasiyana ndipo, chofunikira, zotsatirapo zokhudzana ndi matenda a chigumula ndikuchiritsa. Ngakhale izi mu vitro ndi maphunziro a Vivo ndi maphunziro a Vivo ndi kuwonetsa luso la mavalidwe awa pochiza matenda a bala ndi mankhwala oletsa matenda, mayesero osinthika amafunika kuwunika luso la mavalidwewa kuchipatala.
Zolemba zomwe zimagwiritsidwa ntchito komanso / kapena kusanthula panthawi yomwe kafukufuku wapano amapezeka kuchokera ku Wolemba wolingana ndi zofunsidwa.
Post Nthawi: Jul-15-2024