Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

There is an urgentneed for improved outcomes in the treatmentof pelvic organ prolapse (POP). Success of primary surgery relieson the load bearing capacity of plicated connective tissue underneaththe vaginal wall, which is compromised due to an altered vaginal fibroblastfunction and collagen composition. There is an important factor inconnective tissue repair that relates to changes in stiffness of thevaginal fibroblast microenvironment, which influences cell activitythrough cellular mechanosensing. The aim of this study is to investigatethe effect of stiffness changes on vaginal fibroblast functions thatrelate to connective tissue healing in prolapse repair. The substratestiffness was controlled by changing the polymer concentration inthe fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel.We analyzed stiffness during cell culture and assessed the consequentialfibroblast proliferation, morphology, collagen deposition, and contraction.Our results show that increasing stiffness coincides with vaginalfibroblast alignment, promotes collagen deposition, and inhibits PICgel contraction. These findings suggest that the matrix stiffnessdirectly influences vaginal fibroblast functionality. Moreover, weobserved a buildup in stiffness and collagen, with an enhanced fibroblastand collagen organization on the PIC-substrate, which indicate anenhanced structural integrity of the hydrogel-cell construct. An improvedtissue structure during healing is relevant in the functional repairof POP. Therefore, this study encourages future research in the useof PIC gels as a supplement in prolapse surgery, whereby the hydrogelstiffness should be considered.

Automated summary

This study investigates the effect of substrate stiffness on vaginal fibroblast functions related to connective tissue healing in prolapse repair. The findings show that increasing stiffness promotes collagen deposition and inhibits gel contraction, suggesting a direct influence of matrix stiffness on vaginal fibroblast functionality. This study encourages future research in the use of PIC gels as a supplement in prolapse surgery, considering the hydrogel stiffness.