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

网片并发症:网片植入后局部机械应力对组织重塑的作用

基本信息

项目摘要

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 incorporated flat mesh to that found in deformed mesh. We advocate that defining the mechanistic basis of current complications is a key and necessary step in the iterative process toward improving current meshes and developing future novel devices for POP repair.
项目总结

项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dysregulated wound healing in the pathogenesis of urogynecologic mesh complications.
  • DOI:
    10.1038/s41598-023-48388-8
  • 发表时间:
    2023-12-05
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
  • 通讯作者:
T regulatory cells and TGF-β1: Predictors of the host response in mesh complications.
T调节细胞和TGF-β1:网格并发症中宿主反应的预测指标。
  • DOI:
    10.1016/j.actbio.2020.07.051
  • 发表时间:
    2020-10-01
  • 期刊:
  • 影响因子:
    9.7
  • 作者:
    Artsen AM;Liang R;Meyn L;Rytel M;Palcsey S;Abramowitch SD;Moalli PA
  • 通讯作者:
    Moalli PA
Exploring the basic science of prolapse meshes.
Characterization of the T-cell response to polypropylene mesh in women with complications.
患有并发症的女性中 T 细胞对聚丙烯网片反应的表征。
  • DOI:
    10.1016/j.ajog.2018.11.121
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    9.8
  • 作者:
    Tennyson,Lauren;Rytel,Matthew;Palcsey,Stacy;Meyn,Leslie;Liang,Rui;Moalli,Pamela
  • 通讯作者:
    Moalli,Pamela
Impact of Polypropylene Prolapse Mesh on Vaginal Smooth Muscle in Rhesus Macaque.
  • DOI:
    10.1016/j.ajog.2019.05.008
  • 发表时间:
    2019-05
  • 期刊:
  • 影响因子:
    9.8
  • 作者:
    R. M. Shaffer;R. Liang;K. Knight;C. Carter-Brooks;S. Abramowitch;P. Moalli
  • 通讯作者:
    R. M. Shaffer;R. Liang;K. Knight;C. Carter-Brooks;S. Abramowitch;P. Moalli
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STEVEN D ABRAMOWITCH其他文献

STEVEN D ABRAMOWITCH的其他文献

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{{ truncateString('STEVEN D ABRAMOWITCH', 18)}}的其他基金

Mesh complications: The role of local mechanical stresses on tissue remodeling following mesh implantation
网片并发症:网片植入后局部机械应力对组织重塑的作用
  • 批准号:
    10462766
  • 财政年份:
    2021
  • 资助金额:
    $ 59.79万
  • 项目类别:
Mesh complications: The role of local mechanical stresses on tissue remodeling following mesh implantation
网片并发症:网片植入后局部机械应力对组织重塑的作用
  • 批准号:
    10298638
  • 财政年份:
    2021
  • 资助金额:
    $ 59.79万
  • 项目类别:
Overcoming Complications of Polypropylene Prolapse Meshes: Development of Novel Elastomeric Auxetic Devices
克服聚丙烯脱垂网的并发症:新型弹性拉胀装置的开发
  • 批准号:
    10372098
  • 财政年份:
    2019
  • 资助金额:
    $ 59.79万
  • 项目类别:
Overcoming Complications of Polypropylene Prolapse Meshes: Development of Novel Elastomeric Auxetic Devices
克服聚丙烯脱垂网的并发症:新型弹性拉胀装置的开发
  • 批准号:
    9917810
  • 财政年份:
    2019
  • 资助金额:
    $ 59.79万
  • 项目类别:
Overcoming Complications of Polypropylene Prolapse Meshes: Development of Novel Elastomeric Auxetic Devices
克服聚丙烯脱垂网的并发症:新型弹性拉胀装置的开发
  • 批准号:
    10613362
  • 财政年份:
    2019
  • 资助金额:
    $ 59.79万
  • 项目类别:
Porosity and tensioning: Critical factors to consider when choosing a prolapse mesh
孔隙率和张力:选择脱垂网片时要考虑的关键因素
  • 批准号:
    9205246
  • 财政年份:
    2016
  • 资助金额:
    $ 59.79万
  • 项目类别:
Porosity and tensioning: Critical factors to consider when choosing a prolapse mesh
孔隙率和张力:选择脱垂网片时要考虑的关键因素
  • 批准号:
    9030077
  • 财政年份:
    2016
  • 资助金额:
    $ 59.79万
  • 项目类别:

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