Supramolecular Fibrous Hydrogel Augmentation of Uterosacral Ligament Suspension for Treatment of Pelvic Organ Prolapse

Abstract

Uterosacral ligament suspension (USLS) is a common surgical treatment for pelvic organ prolapse (POP). However, the relatively high failure rate of up to 40% underscores a strong clinical need for complementary treatment strategies, such as biomaterial augmentation. Herein, the first hydrogel biomaterial augmentation of USLS in a recently established rat model is described using an injectable fibrous hydrogel composite. Supramolecularly-assembled hyaluronic acid (HA) hydrogel nanofibers encapsulated in a matrix metalloproteinase (MMP)-degradable HA hydrogel create an injectable scaffold showing excellent biocompatibility and hemocompatibility. The hydrogel can be successfully delivered and localized to the suture sites of the USLS procedure, where it gradually degrades over six weeks. In situ mechanical testing 24 weeks post-operative in the multiparous USLS rat model shows the ultimate load (load at failure) to be 1.70 ± 0.36 N for the intact uterosacral ligament (USL), 0.89 ± 0.28 N for the USLS repair, and 1.37 ± 0.31 N for the USLS + hydrogel (USLS+H) repair (n = 8). These results indicate that the hydrogel composite significantly improves load required for tissue failure compared to the standard USLS, even after the hydrogel degrades, and that this hydrogel-based approach can potentially reduce the high failure rate associated with USLS procedures.

Keywords: hydrogels; nanofibers; pelvic organ prolapse; tissue engineering; uterosacral ligaments.