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Age-associated impairments in tissue strength and immune response in a rat vaginal injury model

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Abstract

Introduction and hypothesis

Surgical repair of pelvic organ prolapse often includes native tissue repair during which the patient’s own vaginal connective tissue is used to achieve pelvic support. This method, based on plication and suspension often yields suboptimal anatomical outcomes, possibly due to inadequate healing of the vaginal connective tissue. We hypothesized that age might have a negative effect on the time course and tissue biomechanics of vaginal wound healing in a rat model.

Methods

Fifty young (12 weeks) and old (12 months) female 344BN Fischer rats were subjected to a posterior midline vaginal incision. The time course of repair was determined by measuring the size of the wound on days 1, 3, 7, and 14 post-injury. These findings correlated with the immune response to injury using a marker of impaired wound healing, the inflammatory cytokine macrophage migration inhibitory factor in the vaginal muscularis. Biomechanical properties of the healed vaginal tissue were tested 30 days post-injury.

Results

Wound healing was assessed on days 1, 3, 7, and 14 post-injury. On day 3 post-injury, the wounds in the young animals had all closed whereas the wounds in the old animals remained open. Furthermore, on day 7, the wound gap was still filled with granulation tissue in the old rats, whereas for the young rats, the wound area was almost indistinguishable from the non-injured area. Macrophage migration inhibitory factor was highly expressed in the vaginal epithelium and in the vaginal muscularis after injury. When compared with young animals, macrophage migration inhibitory factor levels of old rats began to rise more than 2 days later and the increased tissue expression persisted for 7 days longer. The breakpoint force of the healed vagina of old rats was almost 4-fold weaker than in young rats. At 30 days post-injury, the healed vagina in old rats regained less of the original (healthy) force at breakpoint than the young rats.

Conclusions

In this rat model, age impaired vaginal wound healing, which was reflected in the altered inflammatory response to injury and reduced tissue strength.

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Funding

This work was supported by the following NIH grant: NICHD U10-HD047890 (DS and KS).

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Authors and Affiliations

  1. Section of Female Pelvic Medicine & Reconstructive Surgery, Department of Obstetrics & Gynecology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, PO Box 12000, Ein Kerem, Jerusalem, Israel

    David Shveiky & Henry H. Chill

  2. Section of Female Pelvic Medicine & Reconstructive Surgery, Departments of Obstetrics & Gynecology and Urology, Medstar—Washington Hospital Center, Georgetown University, Washington, DC, USA

    Cheryl B. Iglesia

  3. FDA/CDRH/OSEL/Division of Biology, Chemistry, and Materials Science, Silver Spring, MD, USA

    Srilekha Sarkar Das

  4. The Hadassah Human Embryonic Stem Cell Research Center, Goldyne Savad Institute of Gene Therapy, Hadassah—Hebrew University Hospital, Jerusalem, Israel

    Ofra Ben Menachem-Zidon

  5. Center for the Study of Sex Differences in Health, Aging and Disease (CSD), Georgetown University, Washington, DC, USA

    Hong Ji & Kathryn Sandberg

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  1. David Shveiky
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  2. Cheryl B. Iglesia
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  3. Srilekha Sarkar Das
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  4. Ofra Ben Menachem-Zidon
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  5. Henry H. Chill
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  6. Hong Ji
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  7. Kathryn Sandberg
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Correspondence to David Shveiky.

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The findings and conclusions in this paper have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy. The mention of commercial products, their sources, or their use in connection with material reported herein, is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

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Shveiky, D., Iglesia, C.B., Sarkar Das, S. et al. Age-associated impairments in tissue strength and immune response in a rat vaginal injury model. Int Urogynecol J 31, 1435–1441 (2020). https://doi.org/10.1007/s00192-019-04008-6

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  • DOI: https://doi.org/10.1007/s00192-019-04008-6

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