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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >In vivo molecular engineering of the urethra for treatment of stress incontinence using novel biomimetic proteoglycans
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In vivo molecular engineering of the urethra for treatment of stress incontinence using novel biomimetic proteoglycans

机译:在使用新型生物摩擦蛋白转基因的尿道的体内分子工程中的尿道治疗压力尿失禁

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摘要

Stress urinary incontinence (SUI), a serious condition which affects similar to 56% of postmenopausal women, is the involuntary leakage of urine through urethra during physical activity that causes an increase in abdominal pressure. SUI is associated with a decrease in compliance and volume of urethral tissue, likely due to a reduced proteoglycan: collagen ratio in the extracellular matrix and collagen disorganization. Here, we investigated the use of biomimetic proteoglycans (BPGs) to molecularly engineer urethral tissue of New Zealand White rabbits to examine biocompatibility in vivo. BPG concentrations of 50 mg/mL (n = 6, 1 week) and 200 mg/mL (n = 6, 1 week and n = 6, 6 weeks) dissolved in 1x phosphate-buffered saline (PBS) were injected transurethrally using a 9 French cystoscope, and were compared to PBS-injected controls (n = 3, 1 week) and non-injected controls (n = 2, 1 week). Urethral compression pressure measurements confirm BPG injections did not modify normal urethral pressure, as intended. Histological assessment demonstrated biological tolerance of BPGs in urethra and no inflammatory response was detected after 1 and 6 weeks compared to non-injected controls. Confocal imaging of fluorescently-labeled BPG injected urethral specimens demonstrated the integration of BPGs into the interstitial connective tissue and confirmed they were still present after 6 weeks. A general decrease of collagen density was exhibited near injection sites which may be due to increased hydration induced by BPGs. Injection of BPGs is a novel approach that demonstrates potential as molecular treatment for SUI and may be able to reverse some of the degenerative tissue changes of individuals affected by this condition. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2019. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2409-2418, 2019.
机译:压力尿失禁(SUI),一种严重的病情,影响与患绝经后妇女的56%,是尿液通过尿道在物理活性期间尿道的不自愿泄漏,导致腹部压力增加。 SUI与尿道组织的顺应性和体积减少有关,可能由于蛋白多糖降低:细胞外基质和胶原蛋白酶中的胶原蛋白比例。在这里,我们调查了使用仿生蛋白多糖(BPG)的新西兰白兔的分子工程尿道组织,以检查体内生物相容性。用溶解在1x磷酸盐缓冲盐水(PBS)中溶解在1x磷酸盐缓冲盐水(PBS)中的50mg / ml(n = 6,1周)和200mg / ml(n = 6,1,1周和n = 6,6周)的BPG浓度被翻转9法语膀胱镜,并与PBS注入的对照(n = 3,1周)和未注射对照(n = 2,1周)进行比较。尿道压缩压力测量确认BPG注射未按预期修改正常尿道压力。组织学评估表明,与未注射的对照相比,在1和6周后没有检测到尿道中BPG的生物耐受性。荧光标记的BPG注射尿道标本的共焦成像证明了BPG的整合到间质结缔组织中,并确认它们在6周后仍然存在。在注射部位附近呈胶原密度的一般降低,这可能是由于BPGS诱导的水合增加。 BPG的注射是一种新的方法,表明SUI的分子治疗潜力,并且可能能够扭转受这种情况影响的个体的一些退行性组织变化。 (c)2019 Wiley期刊,Inc.J生物保证母乳第B部分B:00B:000-000,2019。(c)2019 Wiley期刊,Inc。J生物保解率A件B:Appl Biomater 107B:2409-2418,2019。

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