Department of Obstetrics and Gynecology, Amsterdam University Medical Center-location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Reproductive Biology Laboratory, Amsterdam Reproduction and Development, Amsterdam University Medical Center-location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3759-3767. doi: 10.1021/acsabm.3c00433. Epub 2023 Aug 17.
There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath the vaginal wall, which is compromised due to an altered vaginal fibroblast function and collagen composition. There is an important factor in connective tissue repair that relates to changes in stiffness of the vaginal fibroblast microenvironment, which influences cell activity through cellular mechanosensing. The aim of this study is to investigate the effect of stiffness changes on vaginal fibroblast functions that relate to connective tissue healing in prolapse repair. The substrate stiffness was controlled by changing the polymer concentration in the fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel. We analyzed stiffness during cell culture and assessed the consequential fibroblast proliferation, morphology, collagen deposition, and contraction. Our results show that increasing stiffness coincides with vaginal fibroblast alignment, promotes collagen deposition, and inhibits PIC gel contraction. These findings suggest that the matrix stiffness directly influences vaginal fibroblast functionality. Moreover, we observed a buildup in stiffness and collagen, with an enhanced fibroblast and collagen organization on the PIC-substrate, which indicate an enhanced structural integrity of the hydrogel-cell construct. An improved tissue structure during healing is relevant in the functional repair of POP. Therefore, this study encourages future research in the use of PIC gels as a supplement in prolapse surgery, whereby the hydrogel stiffness should be considered.
治疗盆腔器官脱垂 (POP) 时，改善治疗效果迫在眉睫。初次手术的成功依赖于阴道壁下方折叠结缔组织的承重能力，由于阴道成纤维细胞功能和胶原组成的改变，这种能力会受到影响。在结缔组织修复中有一个重要因素与阴道成纤维细胞微环境的刚度变化有关，它通过细胞机械感觉来影响细胞活性。本研究旨在探讨刚度变化对与脱垂修复中结缔组织愈合相关的阴道成纤维细胞功能的影响。通过改变纤维状和强仿生聚异氰酸酯 (PIC) 水凝胶中的聚合物浓度来控制基底刚度。我们在细胞培养过程中分析了刚度，并评估了随之而来的成纤维细胞增殖、形态、胶原沉积和收缩情况。研究结果表明，随着刚度的增加，阴道成纤维细胞会排列整齐，促进胶原沉积，并抑制 PIC 凝胶收缩。这些发现表明基质刚度直接影响阴道成纤维细胞的功能。此外，我们观察到在 PIC 基底上的刚度和胶原的积累增加，以及成纤维细胞和胶原的组织增强，这表明水凝胶-细胞构建体的结构完整性得到了增强。在愈合过程中组织结构的改善与 POP 的功能性修复有关。因此，本研究鼓励未来将 PIC 凝胶用作脱垂手术的补充物进行研究，应考虑水凝胶的刚度。
