PDF(Pubmed)
Abstract：
Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the vagina, causing a feeling of bulging, problems in urination, defaecation and/or sexual function. However, the existing surgical repair methods for relapsed POP remain insufficient, highlighting the urgent need for more effective alternatives. Collagen is an essential component in pelvic floor tissues, providing structural support, and its production is controlled by ascorbic acid. Therefore, we investigated novel ascorbic acid 2-phosphate (A2P)-releasing poly(l-lactide-co-ε-caprolactone) (PLCLA2P) membranes in vitro to promote cell proliferation and extracellular matrix protein production to strengthen the natural support of the pelvic fascia for POP applications. We analysed the mechanical properties and the impact of PLCLA2P on cellular responses through cell culture analysis using human vaginal fibroblasts (hVFs) and human adipose-derived stem/stromal cells (hASCs) compared to PLCL. In addition, the A2P release from PLCLA2P membranes was assessed in vitro. The PLCLA2P demonstrated slightly lower tensile strength (2.2 ± 0.4 MPa) compared to PLCL (3.7 ± 0.6 MPa) for the first 4 weeks in vitro. The A2P was most rapidly released during the first 48 h of in vitro incubation. Our findings demonstrated significantly increased proliferation and collagen production of both hVFs and hASCs on A2P-releasing PLCLA2P compared to PLCL. In addition, extracellular collagen Type I fibres were detected in hVFs, suggesting enhanced collagen maturation on PLCLA2P. Moreover, increased extracellular matrix protein expression was detected on PLCLA2P in both hVFs and hASCs compared to plain PLCL. In conclusion, these findings highlight the potential of PLCLA2P as a promising candidate for promoting tissue regeneration in applications aimed for POP tissue engineering applications.
摘要：
盆腔器官脱垂（POP）困扰着全球数百万妇女。在POP中,盆底支撑减弱导致盆腔器官下降到阴道，造成一种鼓胀的感觉，排尿问题，排便和/或性功能。然而,现有的复发性POP手术修复方法仍然不足，强调迫切需要更有效的替代品。胶原蛋白是盆底组织的重要组成部分，提供结构支撑，它的生产受抗坏血酸控制。因此,我们研究了新型的抗坏血酸2-磷酸（A2P）释放聚（1-丙交酯-co-ε-己内酯）（PLCLA2P）膜，以促进细胞增殖和细胞外基质蛋白的产生，以加强骨盆筋膜对POP应用的天然支持。我们通过使用人阴道成纤维细胞(hVFs)和人脂肪来源的干/基质细胞(hASCs)与PLCL相比的细胞培养分析,分析了机械性质和PLCLA2P对细胞反应的影响。此外,在体外评估从PLCLA2P膜的A2P释放。在体外的前4周,PLCLA2P显示与PLCL(3.7±0.6MPa)相比略低的拉伸强度(2.2±0.4MPa)。A2P在体外孵育的前48小时内释放最快。我们的发现表明，与PLCL相比，在释放A2P的PLCLA2P上，hVF和hASC的增殖和胶原蛋白产生显着增加。此外,在hVFs中检测到细胞外I型胶原纤维，提示PLCLA2P上胶原蛋白成熟增强。此外，与普通PLCL相比，在hVFs和hASCs的PLCLA2P上检测到细胞外基质蛋白表达增加。总之,这些发现凸显了PLCLA2P在POP组织工程应用中作为促进组织再生的有希望的候选物的潜力.
