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
- 批准号:10687194
- 负责人:
- 金额:$ 59.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-15 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdvocateAgeApoptosisAreaBiocompatible MaterialsCellsCollagenComplicationComputer ModelsDataDepositionDeteriorationDevelopmentDevicesDiamondDiseaseDisparateDistantEncapsulatedEpitheliumEventExcisionExposure toFailureFiberFibroblastsFibrosisFutureGeometryGrantImmigrationImmune responseIn VitroInflammatoryInjuryMacrophageMechanical StressModelingModificationMolecularMotionMyofibroblastOperative Surgical ProceduresOryctolagus cuniculusOutcomePathologicPathway interactionsPatientsPhenotypePhysiologicalPolypropylenesProcessProliferatingResearchRoleRotationSignal TransductionSiteSmooth MuscleStressSurgeonSymptomsTestingThinnessTimeTissuesTranslatingUnited StatesVaginaVariantWomandesignfunctional outcomesimplantationimprovedin vitro Modelin vivolight weightmechanical signalmillimeternonhuman primatenovelpelvic organ prolapserepairedresponsesoft tissuesurgery outcometissue repair
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.
项目摘要
盆腔器官脱垂(POP)是一种常见的使人衰弱的疾病,困扰着世界各地的妇女。12.6%的
仅在美国,女性在80岁之前就将接受大手术来修复POP。现行做法
使用轻质、针织、宽孔聚丙烯支撑,以改善与
自体组织修复然而,补片的使用受到并发症的限制,最常见的是补片暴露
通过阴道上皮和疼痛,发生在约10%的情况下。此前,使用体外试验和
计算模型,我们表明,大多数POP网格的孔隙几何形状是显着不稳定的,
很容易在施加少量张力的情况下变形,导致收缩的孔隙和褶皱。相比之下,Square
多孔补片稳定,几乎没有变形,转化为整体结构和功能的改善
与几何形状不稳定的补片相比的体内结果。然而,通过旋转方孔网格,
45 o到不稳定的钻石配置和故意引入皱纹,我们成功地复制了
并发症最明显的是与底层变薄和退化相关的网格暴露
表明有压力遮挡一个更微妙的发现是在邻近地区,我们观察到密集的
胶原/基质沉积和组织增厚与纤维化一致,这是一种合理的疼痛机制。
肌成纤维细胞通常不存在于健康组织中,但在补片区域中显著增加
变形,特别是纤维化明显的地方,强烈表明机械信号,发生在一个
高度地方一级,是东道国反应的主要驱动力。因此,虽然我们以前的研究集中在
免疫反应立即在该地区的网状纤维,我们赞赏,更有影响力的事件
在POP生物材料结果中,由成纤维细胞驱动的可能更为关键。总体假设
这一建议是,由补片的张紧和生理负荷引起的局部应力变化,信号
阴道成纤维细胞的增殖与降解反应与静止,
机械提示为了解决这一假设,在目标1中,我们定义了阴道成纤维细胞对改变的
在a)体内家兔阴道固定模型和B)体外模型中,补片随时间施加的机械应力
使用提供成纤维细胞机械信号传导的功能化合成可调基质。在目标2中,我们测试
假设过度张拉稳定的孔隙网格对主机响应有负面影响,
应力变异性而高应力区域将诱导肌成纤维细胞增殖和基质/胶原沉积
随着收缩,亚生理(屏蔽)应力区域将导致基质降解和成纤维细胞凋亡。
在目标3中,我们解释了从患有并发症的女性中取出补片的先前目标的结果,
将正常结合的扁平补片中的成纤维细胞和免疫反应与变形补片中的成纤维细胞和免疫反应进行比较,
网格我们主张,确定目前并发症的机制基础是关键和必要的一步,
改进当前网格和开发未来用于POP修复的新型设备的迭代过程。
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.
- DOI:10.1097/gco.0000000000000313
- 发表时间:2016-10
- 期刊:
- 影响因子:2.1
- 作者:Liang R;Knight K;Abramowitch S;Moalli PA
- 通讯作者:Moalli PA
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
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
STEVEN D ABRAMOWITCH其他文献
STEVEN D ABRAMOWITCH的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
相似海外基金
Optimizing Health and Well-Being of Diverse Mothers with IDD and Their Infants During the Perinatal Period: A Virtual Advocate Tool for Data-Driven Supports
优化患有 IDD 的不同母亲及其婴儿在围产期的健康和福祉:用于数据驱动支持的虚拟倡导工具
- 批准号:
10760051 - 财政年份:2023
- 资助金额:
$ 59.79万 - 项目类别:
POSE: Phase II: Advocate Led Long-term Gameplan for Open OnDemand (ALL GOOD)
POSE:第二阶段:倡导者主导 Open OnDemand 的长期游戏计划(一切顺利)
- 批准号:
2303692 - 财政年份:2023
- 资助金额:
$ 59.79万 - 项目类别:
Standard Grant
Capitalising on our differences: A gathering to better understand and advocate for Early Career Health Researchers in Canada
利用我们的差异:更好地理解和倡导加拿大早期职业健康研究人员的聚会
- 批准号:
468168 - 财政年份:2022
- 资助金额:
$ 59.79万 - 项目类别:
Miscellaneous Programs
Addressing social adversity to improve outcomes among children undergoing liver transplant: the role for a health advocate on the transplant team
解决社会逆境以改善接受肝移植的儿童的预后:移植团队中健康倡导者的作用
- 批准号:
10427960 - 财政年份:2022
- 资助金额:
$ 59.79万 - 项目类别:
Evaluating an ACEs-Targeting Advocate Model of a Substance Use Prevention Program
评估药物使用预防计划的针对 ACE 的倡导者模型
- 批准号:
10577074 - 财政年份:2022
- 资助金额:
$ 59.79万 - 项目类别:
The Art of Creation: Using Art-Based Knowledge Translation to Promote and Advocate for a Healthy Start to Life
创造的艺术:利用基于艺术的知识转化来促进和倡导健康的生命开端
- 批准号:
486588 - 财政年份:2022
- 资助金额:
$ 59.79万 - 项目类别:
Studentship Programs
When I am Old, I shall Wear Purple Nail Varnish: Utilising performance art to construct queer spaces that celebrate and advocate for ageing bodies
当我老了,我要涂紫色指甲油:利用行为艺术构建酷儿空间,庆祝和倡导衰老的身体
- 批准号:
2760091 - 财政年份:2022
- 资助金额:
$ 59.79万 - 项目类别:
Studentship
Addressing social adversity to improve outcomes among children undergoing liver transplant: the role for a health advocate on the transplant team
解决社会逆境以改善接受肝移植的儿童的预后:移植团队中健康倡导者的作用
- 批准号:
10621188 - 财政年份:2022
- 资助金额:
$ 59.79万 - 项目类别:
Techquity by FAITH!: A cluster randomized controlled trial to assess the efficacy of a community-informed, cardiovascular health promotion mobile hlth intervention with digital health advocate support
Techquity by FAITH!:一项整群随机对照试验,旨在评估社区知情、心血管健康促进移动 hlth 干预措施在数字健康倡导者支持下的效果
- 批准号:
10891016 - 财政年份:2021
- 资助金额:
$ 59.79万 - 项目类别:
CMV responses in autoantibody positive subjects advocate antiviral treatments for prevention of T1D
自身抗体阳性受试者的 CMV 反应主张抗病毒治疗以预防 T1D
- 批准号:
10230365 - 财政年份:2020
- 资助金额:
$ 59.79万 - 项目类别: