Wound Healing Society

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A Thermogelling Hyaluronic Acid Vaginal Stent to Reduce Postoperative Vaginal Scarring
Omar Wyman1, Swathi Balaji2, Sundeep Keswani2, Julie Hakim2.
1University of Oklahoma, Norman, OK, USA, 2Texas Children's Hospital, Houston, TX, USA.

Background: Vaginal fibrosis is a debilitating problem effecting 50,000 girls and 213,000 adult women yearly in the USA, who require vaginal reconstructive surgery with 73% experiencing postoperative fibrotic sequelae. Standard-of-care includes local delivery of conjugated estrogen (CEE) creams in combination with vaginal stents, which are ineffective. Previous work in our lab has shown that hyaluronic acid (HA)-based therapeutics reduce fibrosis and promote regenerative wound healing. The goal of this study is to determine the mechanisms of how hyaluronic (HA) and β-estradiol (E2)-based therapies regulate post-injury vaginal tissue repair.

Methods: First time development of a minimally-invasive murine intra-vaginal model to study full-thickness vaginal wounds in pre-estrus (4wk) CD1 female mice. We compared the effect of daily local estrogen delivery with CEE cream to sustained estrogen delivery with a novel E2-eluding Norb-HA hydrogel on vaginal wound healing. Wounds were harvested at 6,12,18,24,48,72,&120h post-injury(n=6/group), analyzed for wound healing by morphometric analysis(H&E) and modified Vaginal Scar Scoring(VSS), inflammation and angiogenesis by Macrophage inhibiting factor 1(MIF1), TGFβ1 and VEGF (qRT-PCR), and ECM by qRT-PCR for Col1, Col3, MMP2 and MMP9. p-values by ANOVA.

Results: The kinetics of murine vaginal wound healing demonstrated an accelerated healing profile with resolution of mucosal integrity by 48h with decrease in proximal acute inflammation assessed by VSS (p<0.01). A statistically significant decrease in MIF1 expression was found in wounds treated with our novel HA-hydrogel estrogen (Norb-HA/E2) delivery vehicle compared to CEE cream at day 10. Norb-HA/E2 treatment also increased TGFβ1, TIMP1 and COL3/COL1 ratio (p<0.01) by day 10, and decreased MMP9 by day 5 (p<0.01).

Conclusions: It appears that murine mucosal vaginal tissue heals with an accelerated timeline. Our novel vaginal HA-based hydrogel with sustained E2 release improves both anti-inflammatory and indirect pro-angiogenic effects of exogenous E2, enhances vaginal tissue healing compared to local exogenous estrogen cream. Further development of this platform may provide substantial increase in efficacy of E2 delivery to vaginal tissue and reduce post-operative vaginal fibrosis.

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