# Mesh complications: The role of local mechanical stresses on tissue remodeling following mesh implantation

> **NIH NIH R01** · MAGEE-WOMEN'S RES INST AND FOUNDATION · 2024 · $591,883

## Abstract

PROJECT SUMMARY
Pelvic organ prolapse (POP) is a common debilitating disease afflicting women throughout the world. 12.6% of
women in the United States alone will undergo a major surgery to repair POP by age 80. Current practice
supports using lightweight, knitted, wide pore polypropylene to improve the high failure rates associated with
native tissue repair. However, mesh use has been limited by complications, most commonly mesh exposure
through the vaginal epithelium and pain, occurring in ~10% of cases. Previously, using ex vivo tests and
computational models, we showed that the pore geometries of most POP meshes were markedly unstable,
easily deforming with small applications of tension, resulting in collapsed pores and wrinkling. In contrast, square
pored meshes were stable showing little deformation, translating into overall improved structural and functional
outcomes in vivo as compared to meshes with unstable geometries. However, by rotating square pored meshes
45o to an unstable diamond configuration and intentionally introducing wrinkles, we successfully reproduced
complications. Most obvious were mesh exposures associated with thinning and degeneration of the underlying
vagina indicative of stress shielding. A more subtle finding was in adjacent areas where we observed dense
collagen/matrix deposition and tissue thickening consistent with fibrosis, a plausible mechanism of pain.
Myofibroblasts, not typically present in healthy tissues, were dramatically increased in areas of mesh
deformation, particularly where fibrosis was evident, strongly suggesting that mechanical signals, occurring at a
highly local level, were a primary driver of the host response. Thus, while our previous studies had focused on
the immune response immediately in the area of the mesh fiber, we appreciated that more impactful events
driven by fibroblasts were perhaps even more critical in POP biomaterial outcomes. The overall hypothesis of
this proposal is that local stress variations induced by tensioning and physiologic loading of mesh, signal
vaginal fibroblasts toward a proliferative vs degradative response vs quiescence based on local
mechanical cues. To address this hypothesis, in Aim 1, we define the response of vaginal fibroblasts to altered
mechanical stresses imposed by mesh over time in a) an in vivo rabbit colpopexy model; and b) an in vitro model
using a functionalized synthetic tunable matrix that affords fibroblast mechanosignaling. In Aim 2, we test the
hypothesis that over tensioning a stable pore mesh has negative impact on the host response by increasing
stress variability. While high stress areas will induce myofibroblast proliferation and matrix/collagen deposition
with contraction; subphysiologic (shielded) stress areas will lead to matrix degradation and fibroblast apoptosis.
In Aim 3, we interpret findings from the previous aims in mesh removed from women with complications by
comparing the fibroblast and immune responses in normally incorp...

## Key facts

- **NIH application ID:** 10894135
- **Project number:** 5R01HD083383-09
- **Recipient organization:** MAGEE-WOMEN'S RES INST AND FOUNDATION
- **Principal Investigator:** STEVEN D ABRAMOWITCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $591,883
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894135

## Citation

> US National Institutes of Health, RePORTER application 10894135, Mesh complications: The role of local mechanical stresses on tissue remodeling following mesh implantation (5R01HD083383-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894135. Licensed CC0.

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