Umbhali: (1) Fatemeh Azari, I-Department of Mechanical Engineering and Materials Science, I-University of Pittsburgh, 3700 O'Hara Street Benedum Hall of Engineering, Pittsburgh, PA 15261 (FAA104@pitt.edu); (2) Anne M. Robertson, I-Department of Mechanical Engineering and Materials Science, i-University of Pittsburgh, 3700 O'Hara Street Benedum Hall of Engineering, Pittsburgh, PA 15261 kanye ne-Department of Bioengineering, i-University of Pittsburgh, 3700 O'Hara Street Benedum Hall of Engineering, Pittsburgh, PA 15261 (rbertson@pitt.edu); (3) Lori A. Birder, i-Department of Medicine, i-University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15213 kanye ne-Department of Pharmacology and Chemical Biology, i-University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15213 (lbirder@pitt.edu). Authors: (1) Fatemeh Azari, I-Department of Mechanical Engineering and Materials Science, I-University of Pittsburgh, 3700 O'Hara Street Benedum Hall of Engineering, Pittsburgh, PA 15261 (FAA104@pitt.edu); (2) Anne M. Robertson, I-Department of Mechanical Engineering and Materials Science, i-University of Pittsburgh, 3700 O'Hara Street Benedum Hall of Engineering, Pittsburgh, PA 15261 kanye ne-Department of Bioengineering, i-University of Pittsburgh, 3700 O'Hara Street Benedum Hall of Engineering, Pittsburgh, PA 15261 (rbertson@pitt.edu); (3) Lori A. Birder, i-Department of Medicine, i-University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15213 kanye ne-Department of Pharmacology and Chemical Biology, i-University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15213 (lbirder@pitt.edu). Umbala we-Left Umhlahlandlela & 1 Introduction Imikhiqizo Iziphumo, Iziphumo, kanye nokuxhumana Ukubalwa Izimodeli zokusebenza ezivamile ze-bubble zihlanganisa kakhulu i-bubble njengoba i-spherical nge ububanzi obuningi. Le nkqubo yokusebenza esiyinhlanganisa ukusetshenziswa kwe-micro-CT ukukhiqiza amamodeli ze-3D ezihlangene ze-rat blader at 10-20 micrometer resolution ezimbini ezihlangene nezimo ezihlangeneyo nezimo ezihlangeneyo. Isetshenziselwa ama-bat blader ezihlangeneyo ezintathu, le ndlela ibonise-ukwakha, umthamo, nezimo ezihlangeneyo ngaphansi kwezimo ezahlukahlukene. Lezi ziphumela zibonisa inqubo yokufaka / yokufaka kuyinto emangalisayo ye-spherical inflation / contraction. Nokho, i-geometry i-idealizations ing 1 Ukulungiswa Ukusebenza kwe-bubble surge isekelwe yi-geometry, ububanzi be-wall, kanye nemikhiqizo ye-biomechanical, zonke ezinzima ukuphazamiseka ngenxa ye-aging kanye nemiphumela emzimbeni, eyakhiwe yi-BOO. Umthombo we-BOO kwebolondoloza ngokuvumelana ne-global escalating prevalence ye-benign prostatic hyperplasia (BPH), umphumela esisodwa we-BOO. I-BPH ibonise ukwanda we-70.5% kusuka ku-51.1 million imizuzu ku-2000 kuya ku-94 million ku-2019 [1.2,3] futhi iyinkinga elikhulu lwezokwelapha kumadoda angu-50-60 ubudala kusuka emzimbeni angu-socio-economic engaphansi. I-BPH ibonise i- Ngokuvamile, indlela yokukhipha ukwahlukanisa izigulane ze-BOO iye iye i-ultrasound; kunjalo, ayikwazi ukunikezela ukubuyekeza okuhlobene nezimo ezivela ekukhiqizeni kwezicubu kanye nokuguqulwa. Kusukela ngo-1991, kukhona ukubuyekezwa okuqhubekayo kwezakhiwo ze-BW ngesikhathi kwezicubu zokuphefumula kanye nokugqwala. Nokho, le nkqubo yokuhlola lithathwa ngenxa yokungabazeka kwezindlela ze-interdisciplinary ezihlanganisiwe kanye nezinsizakalo eziphambili ezidingekayo [4,5,6]. I-literature esiyingekayo yenzulululwazi ibonisa izindlela ezimbili eziphambili zokuhlola izakhiwo ze-BW: Ukuhlolwa kwenziwa kwamanani ne-organ kanye Ngaphezu kwalokho, izindlela ezivamile ze-bubble mechanics characterization zihlanganisa ngokuvamile imodeli ye-bubble ephakeme kakhulu, zihlanganisa njenge-spherical edolobheni enhle enhle. Nakuba lezi zihlanganisa kungenziwa ngokufanelekileyo eminye izakhiwo, zihlanganisa i-geometry ephakeme ye-organ kuhlanganise ukuguqulwa kwe-non-uniform wall thickness ngesikhathi sokugeleza inqubo. Amamodeli amakhulu e-bubble zihlanganisa ukuze zihlanganisa ngokuvumelana ne-bubble biomechanical ephakeme. Ngokuphendula kulesi khulula, isifundo lethu isetshenziselwa micro-CT ukuze zihlanganise ngokufanele izakhiwo ze-bubble wall ku-ex-vivo 2 Izindlela I-Ex-Vivo Filling ye-Urinary Bladder Organ I-cec, i-ureters, ne-urethra eyenziwe ngempumelelo kwama-3-3-3-month-old Sprague-Dawley rats amaphilisi futhi asetshenziswe ngokushesha ku-HEPES-buffered physiological saline solution (HB-PBS) nge-composition ye-134 mM NaCl, 6 mM KCl, 1 mM MgCl2, 2 mM MgCl2, 10 mM HEPES, ne-7 mM glucose, eyenziwe ku-pH 7.4. I-Calcium channel blockers asetshenziswe isisombululo yokuvimbela ukucindezeleka kwe-spontaneous muscle cells (SMC). I-ureters asetshenziswe ngokufanayo ne-bubble wall kanye ne-urethra ehlangan I-Micro-CT Experimental Design kanye ne-Morphological Analysis Ukulungiselela ukufinyelela kwama-model ye-3D ye-bubble eyodwa zihlanganisa i) ukulungiswa, ukuguqulwa kanye nokucaciswa usebenzisa i-scanner ye-High-Resolution Skyscan 1272 (i-Bruker Micro-CT, Kontich, Belgium), ii) ukuguqulwa kwe-3D ye-micro-CT Z ama-stack ye-images e-2D usebenzisa i-software ye-Nrecon (i-Bruker MicroCT, Kontich, Belgium), iii) ukucubungula kwe-morphological ye-3D model usebenzisa i-Simpleware ScanIP software (i-Synopsys, Sunnyvale, California), iv), ukucubungula kwe-3D ye-internal (lumen) ne-external (lumaben) ge Ukuhlolwa kwe-micro-CT kwenziwa usebenzisa i-voltage ye-80 kV kanye ne-125 μA. Izithombe ziye zitholwe ngesilinganiso se-pixel angu-10.8 μm usebenzisa isinyathelo se-rotating angu-0.6 degrees, usayizi se-2048 x 2048 ngaphandle kokulinganisa, futhi isikhathi se-exposure angu-400 ms. Ukuguqulwa kwezi zithombe nge-software ye-NRecon zihlanganisa ukuhlaziywa ngesilinganiso se-15, ukuxhumana ne-ring artifacts ku-50%, futhi ukuguqulwa kwebhizinisi se-stereolithography (STL) idatha angu-2%. Ixesha le-scanning ye-STL ye-bladders lihlanganiswa engaphansi kuka-10 imiz 3 Iziphumo kanye neziphumo Ukubuyekezwa kwe-quantitative geometry ye-bubble eyatholakala kumakhemikhali ezintathu we-bubble ye-rat, eyenziwe njenge-Bladder A, B, ne-C, Isithombe 2. Iziqu ze-data eyatholakala kwizimo ezimbili ze-inflation: (1) zihlukile (i-non-distended state - i-collected condition) kanye (2) zihlukile (distended). Iziphumo ze-bubble-specific morphology zithunyelwe ku-Table 1. Kwi-state emangalisayo, ububanzi we-wall was highly non-uniform. Kwi zonke izimo ezintathu, i-BW ye-state emangalisayo iye kakhulu emangalisayo ekubeni kunezindawo ze-bubble kanye ne-trigonal. Ngokuvamile, ububanzi obuningi obuningi we-cube we-bubble we-three blade was 2.84 mm ±0.28 mm kanti ububanzi obuningi we-middle and trigonal areas was 0.65 ±0.14, ngokuvamile. Ngokungafani, ngesikhathi lokuphuma (i-Fig. 2, b, d, f), zonke ama-blade has a relatively uniform, ubukhulu obuningi nge-median ubukhulu we-0.10mm ±0.02mm. Izimodeli eziningi ze-wall, kuhlanganise nathi [3], zihlanganisa i-bubble nge-spherical configuration kanye ne-homogeneous wall thickness [3,6,10], i-approximation eyenza yokufinyelela izixazululo ze-analytical. Ukusebenza okuzenzakalelayo ibonisa ukuthi kungcono ukufinyelela okuhle kwizifundo lapho i-bubble geometry eyenziwe kubalulekile. Ngokwesibonelo, emisha esifundeni yokukhula nokuguqulwa kwe-BOO bladders, i-bubble eyenziwe (i-spherical) isetshenziselwa njenge-reference configuration yokufinyelela i-homeostatic stretch phakathi kwamafibre ye-collagen kanye namaseli amancane [3]. Nokho, kungenzeka ukuthi Ngokuphathelene, le ncwadi linikeza ukunambitheka ukusetshenziswa kwezimo zokukhipha, njenge-high-resolution micro-CT, ukuhlola i-morphology ye-bubble kanye nokukwazi ukucubungula izicathulo zangaphakathi kwezicathulo ze-wall ngalinye inqubo ye-filling kanye nokukhipha. Lezi zebhizinisi ze-high-resolution zihlanganisa imiklamo yekhompyutha ye-bubble ebonakalayo ukuhlola ukusebenza kwe-bubble ngesikhathi kwezifo ezifana ne-bubble outlet obstruction (BOO). Abacwaningi wabhala ukunakekelwa kwabo ngenxa yokuthumela eyenziwa kusuka ku-NIH-R01 AG056944 ne-NIH-R01 DK133434. Imibuzo [1] Awedew, A. F., et al. I-global, ye-regional, ne-national burden of benign prostatic hyperplasia e-204 amazwe kanye nama-territories kusukela ngo-2000 kuya ku-2019: uchungechunge olusebenzayo ye-Global Burden of Disease Study 2019. The Lancet Healthy Longevity, 3(11), e754-e776, 2022. [2] Fusco, F., et al. Ukuguqulwa okuqhubekayo kwebhulethi ngenxa yokukhula kwebhulethi: ukubuyekezwa okuqhubekayo kwezindaba ze-morphological ne-molecular kumadoda. BMC urology, 18, 1-11, 2018. [3] Cheng, F., et al. Umklamo we-mixture-micturition-growth (CMMG) we-bubble ye-urinary: Ukusetshenziswa kwe-blase partial outlet obstruction (BOO). I-Journal of the mechanical behavior of biomedical materials, 134, 105337, 2022. [4] Damaser, M. S. et al. Ukumiswa kwe-Outlet ye-Outlet iholide ukuphazamiseka kwe-chronic and increased stiffness of the rat urinary bladder. Neurourology and Urodynamics: I-Journal Official of the International Continence Society, 15(6), 650-665, 1996. [5] Parekh, A., et al. I-ex vivo deformations ye-couricle wall ngesikhathi sokuphuma kwe-couricle ephelele: Izinzuzo ze-matrix extracellular kanye ne-muscle smooth. I-Journal of Biomechanics, 43(9), 1708-1716, 2010. [6] Trostorf, R., et al. Isifundo se-pilot ye-characterization esebenzayo ne-ex vivo ye-bubble ye-urinary kanye nemiphumela yayo ku-tridimensional modeling. Journal of the mechanical behavior of biomedical materials, 133, 105347, 2022. [7] Trostorf, R., et al. I-Location-and-layer-dependent biomechanical and microstructural characterization of the porcine bladder wall. I-Journal of the mechanical behavior of biomedical materials, 115, 104275, 2021. [8] Hanczar, M., et al. Ukubaluleka kwe-Biomechanics ne-Scaffold Structure ku-Bladder Tissue Engineering. I-International Journal of Molecular Sciences, 22(23), 12657, 2021. [9] Ajalloueian, F., et al. I-biomechanics ye-Bladder kanye nokusetshenziswa kwe-staffolds ye-regenerative medicine emzimbeni wesibeletho. I-Nature Reviews Urology, 15(3), 155-174, 2018. [10] Hennig, G., et al. Ukubalwa biomechanics jikelele ibhodlela usebenzisa uhlelo entsha pentaplanar ukubonisa image macroscopy. Biomechanics and Modeling in Mechanobiology, 1- 11, 2023. [11] Damaser, M. S. I-whole bladder mechanics ngesikhathi sokupholisa. Scandinavian Journal of Urology and Nephrology, 33(201), 51-58, 1999 [12] “X-ray micro-ct analysis,” DigiM Solution, https://digimsolution.com/services/imaging/xray-micro-ct-analysis, 2023 [13] Birder, L. A., et al. I-Hypoxanthine inikeza izici ze-Bladder Aging nge-Voiding Dysfunction ne-Lower Urinary Tract Remodeling. I-Journals of Gerontology: I-Series A, glad171, 2023. Okuzenzakalelayo iyatholakala ku-archiv ngaphansi kwe-license CC BY 4.0 DEED. Okuzenzakalelayo Ngaphansi kwe-license CC BY 4.0 DEED. available on arxiv I-Archive ye-Archive
