De Vita, R. | Search bioRxiv

bioRxiv2024

Biomechanical and Compositional Changes in the Murine Uterus with Age

The uterus is a hollow, fibromuscular organ involved in physiologic processes such as menstruation and pregnancy. The content and organization of extracellular matrix constituents such as fibrillar collagen dictates passive (non-contractile) biomechanical tissue function; however, how extracellular matrix composition and biomechanical function change with age in the uterus remains unknown. This study utilizes Raman spectroscopy coupled with biaxial inflation testing to investigate changes in the murine uterus with age (2-3 months, 4-6 months, 10-12 months, and 20-24 months). Linear and toe moduli significantly decreased with reproductive aging (2 to 12 months); however, moduli increased in the oldest age group (20-24 months). The optical signature of combined elastin and collagen content was significantly higher in the oldest group (20-24 month), while the glycogen contribution was the highest in the 2-3 month murine uterus. The presented workflow couples biaxial inflation testing and Raman spectroscopy, representing a critical first step to correlating biomechanics and optical signatures in the aging uterus with the potential for clinical translation. Further, this study may provide critical compositional and structure-function information regarding age-related uterine disorders.

bioengineering↗

bioRxiv2023

Supramolecular fibrous hydrogel augmentation of uterosacral ligament suspension for treatment of pelvic organ prolapse

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, we describe the first hydrogel biomaterial augmentation of USLS in a recently established rat model 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 6 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 could potentially reduce the high failure rate associated with USLS procedures.

bioengineering↗