Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque.
Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque.
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DOI：
10.1016/j.ajog.2016.09.073
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发表时间：
2017-02
影响因子：
9.8
通讯作者：
Moalli PA
中科院分区：
文献类型：
--
作者：
Liang R;Knight K;Barone W;Powers RW;Nolfi A;Palcsey S;Abramowitch S;Moalli PA
使用宽孔轻质聚丙烯补片改善脱垂手术修复的解剖结局受到补片并发症的阻碍。已发现其中一种原型脱垂补片通过诱导平滑肌体积和收缩力减少以及关键结构蛋白（胶原蛋白和弹性蛋白）降解对阴道产生负面影响，导致阴道变性。近年来，来源于细胞外基质的生物支架已被用于介导组织再生，并已广泛应用于组织工程应用中。我们的目标是：（1）确定在灵长类动物骶骨阴道固定术模型中使用细胞外基质再生移植物增强聚丙烯脱垂补片是否可以缓解退行性变化;（2）确定单独植入时细胞外基质移植物对阴道的影响。通过骶骨阴道固定术将聚丙烯-细胞外基质复合移植物（n = 9）和单独的6层细胞外基质移植物（n = 8）植入17只中年经产恒河猴，并与从假手术（n = 12）和通过相同方法植入的聚丙烯补片（n = 12）获得的历史数据进行比较。阴道功能在被动（球形爆破试验）和主动（平滑肌收缩性）机械试验中测量。阴道组织形态学/生化评估包括苏木精-伊红和三色染色、α-平滑肌肌动蛋白和凋亡细胞的免疫荧光标记、总胶原蛋白、胶原蛋白亚型（III/ I比值）、成熟弹性蛋白和硫酸化糖胺聚糖的测量。统计分析包括单因素方差分析、Kruskal-Wallis和适当的事后检验。与单独植入聚丙烯补片相比，植入复合补片的阴道中的宿主炎症反应减少。在聚丙烯补片中观察到的凋亡细胞增加在复合材料中是钝化的（总体P <0.001）。被动力学测试显示，单独聚丙烯补片和复合补片的参数均劣于假手术组，而复合补片中平滑肌层的收缩性和厚度得到改善，数值与假手术组相似，这与单独聚丙烯补片观察到的降低不同。生物化学上，复合材料具有相似的成熟弹性蛋白含量、硫酸化糖胺聚糖含量和胶原亚型III/I比率，但与假手术相比，总胶原含量较低（P = .011）。单独多层细胞外基质移植物在阴道的生物力学、组织形态学或生物化学终点方面显示出与假手术相比的总体值。单独使用细胞外基质移植物的胶原亚型比率III/I增加（与假手术相比P = 0.033）与持续的主动重塑反应一致。使用再生细胞外基质移植物进行补片填充可减轻聚丙烯补片对阴道的负面影响。单独应用细胞外基质移植物没有可测量的负面影响，表明当在没有永久性材料的情况下使用时，这种细胞外基质移植物的益处出现。未来的研究将集中在了解机制。
The use of wide pore lightweight polypropylene mesh to improve anatomical outcomes in the surgical repair of prolapse has been hampered by mesh complications. One of the prototype prolapse meshes has been found to negatively impact the vagina by inducing a decrease in smooth muscle volume and contractility and the degradation of key structural proteins (collagen and elastin), resulting in vaginal degeneration. Recently, bioscaffolds derived from extracellular matrix have been used to mediate tissue regeneration and have been widely adopted in tissue engineering applications. Here we aimed to: (1) define whether augmentation of a polypropylene prolapse mesh with an extracellular matrix regenerative graft in a primate sacrocolpopexy model could mitigate the degenerative changes; and (2) determine the impact of the extracellular matrix graft on vagina when implanted alone. A polypropylene-extracellular matrix composite graft (n = 9) and a 6-layered extracellular matrix graft alone (n = 8) were implanted in 17 middle-aged parous rhesus macaques via sacrocolpopexy and compared to historical data obtained from sham (n = 12) and the polypropylene mesh (n = 12) implanted by the same method. Vaginal function was measured in passive (ball-burst test) and active (smooth muscle contractility) mechanical tests. Vaginal histomorphologic/ biochemical assessments included hematoxylin-eosin and trichrome staining, immunofluorescent labeling of α-smooth muscle actin and apoptotic cells, measurement of total collagen, collagen subtypes (ratio III/ I), mature elastin, and sulfated glycosaminoglycans. Statistical analyses included 1-way analysis of variance, Kruskal-Wallis, and appropriate posthoc tests. The host inflammatory response in the composite mesh-implanted vagina was reduced compared to that following implantation with the polypropylene mesh alone. The increase in apoptotic cells observed with the polypropylene mesh was blunted in the composite (overall P < .001). Passive mechanical testing showed inferior parameters for both polypropylene mesh alone and the composite compared to sham whereas the contractility and thickness of smooth muscle layer in the composite were improved with a value similar to sham, which was distinct from the decreases observed with polypropylene mesh alone. Biochemically, the composite had similar mature elastin content, sulfated glycosaminoglycan content, and collagen subtype III/I ratio but lower total collagen content when compared to sham (P = .011). Multilayered extracellular matrix graft alone showed overall comparable values to sham in aspects of the biomechanical, histomorphologic, or biochemical end-points of the vagina. The increased collagen subtype ratio III/I with the extracellular matrix graft alone (P = .033 compared to sham) is consistent with an ongoing active remodeling response. Mesh augmentation with a regenerative extracellular matrix graft attenuated the negative impact of polypropylene mesh on the vagina. Application of the extracellular matrix graft alone had no measurable negative effects suggesting that the benefits of this extra-cellular matrix graft occur when used without a permanent material. Future studies will focus on understanding mechanisms.