Best Overall Paper: Acellular Tissue-Specific Biomaterial for Combating Menopausal Vaginal Changes

Objectives: Genitourinary syndrome of menopause (GSM) affects ~85% of (peri)menopausal women. GSM-associated thinning of the vaginal epithelium, deterioration of the extracellular matrix (ECM), and smooth muscle atrophy result in vaginal dryness, decreased tissue elasticity, dyspareunia, irritative lower urinary tract symptoms, and pelvic pain. Despite its high prevalence and negative impact on quality of life, women’s satisfaction with existing GSM treatments is only 35%, due to high cost (vaginal estrogen), poor long-term efficacy (lubricants, moisturizers), or uncertain safety and efficacy (SERMs, laser therapy).

Biocompatible decellularized ECM biomaterials enhance endogenous remodeling of tissues in a variety of disease states and injuries by modulating the immune response, and inducing neovascularization, cellular proliferation, and ECM remodeling. We assessed the impact of a tissue-specific vaginal ECM biomaterial (vECM) on vaginal tissue properties in an established preclinical model of menopause.

Methods: Porcine full-thickness vaginal tissue was minced, decellularized in sodium dodecyl sulfate, lyophilized, milled, and enzymatically digested to produce vECM, which formed a hydrogel after incubation at 37 °C. Ovariectomized (OVX) Sprague Dawley rats were housed for 2 weeks, after which 500 µL of fluorescently prelabeled 8 mg/mL vECM was delivered intravaginally. Animals were euthanized 1, 2, or 3 days after a single vECM administration to assess material retention in the vagina (Fig. A-B). To assess the therapeutic efficacy, rats were randomized to receive 500 µL of daily intravaginal vECM or saline (N=4-9/group), and then euthanized after a 2-week treatment. Vaginas were harvested and processed for the evaluation of epithelial thickness and smooth muscle content.

Results: We observed retention of vECM in the vaginal canal out to 3 days post-administration, with increased cellular presence co-localized with the vECM present in the vaginal canal (Fig. A), suggesting cellular migration to topically administered vECM. Additionally, we observed vECM in the subepithelial tissues following topical administration (Fig. B). We observed significant improvement in vaginal epithelial thickness in vECM treated animals (32.37 ± 6.29 µm, Fig. C) compared to saline (19.00 ± 1.59 µm, Fig. D,E) controls, P< 0.0001. Additionally, we observed a significantly increased smooth muscle layer thickness in the vECM group (54.02 ± 10.56 µm, Fig. F) as compared to the saline group (35.07 ± 7.80 µm, Fig. G), P< 0.05, indicating the vECM improves both epithelial and smooth muscle regeneration in a model of menopause when delivered as a topical formulation.

Conclusions: vECM warrants further investigation as a promising nonhormonal acellular therapeutic alternative to currently available treatments for GSM.

Figure: A. Prelabeled vECM retained for 3 days in the vaginal lumen (L,white). B. vECM in subepithelial and fibromuscular layers. C,D,E. Vaginal cross-sections (H&E (C,D); anti α-smooth muscle actin (F,G)) demonstrating significantly greater epithelial (E) and smooth muscle (M) thickness in vECM vs saline group (H).