Mechanobiology and Regenerative Medicine

力学生物学和再生医学

• 批准号: 7843498
• 负责人: Stephen F. Badylak
• 金额: $ 36.22万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7843498
• 关键词: Address; Affect; Architecture; Biocompatible Materials; Biomechanics; Biomedical Engineering; Bladder; Bladder Tissue; Blood Vessels; Canis familiaris; Cell-Matrix Junction; Cells; Clinical; Clinical Medicine; Collagen Fiber; Consultations; Cystectomy; Dermal; Distal; Engineering; Environment; Esophageal; Esophagus; Evaluation; Event; Extracellular Matrix; Family suidae; Gastrointestinal tract structure; Government; Harvest; Head; Image; Implant; In Vitro; Indigenous; Institutes; Intestines; Laboratories; Lead; Link; Lower urinary tract; Mechanics; Methods; Modeling; Musculoskeletal; Natural regeneration; Nature; Normal tissue morphology; Nutrient; Organ; Organ Culture Techniques; Organ Harvestings; Outcome; Outcome Measure; Oxygen measurement, partial pressure, arterial; Pathologist; Pattern; Perfusion; Persons; Phenotype; Physicians; Physiological; Process; Protocols documentation; Rattus; Regenerative Medicine; Regimen; Role; Site; Smooth Muscle; Smooth Muscle Myocytes; Source; Specimen; Stimulus; Structure; System; Temperature; TimeLine; Tissue Engineering; Tissues; Translating; Translations; United States National Institutes of Health; Veterinarians; Work; biomechanical engineering; cell motility; cell type; clinical application; conditioning; experience; functional outcomes; in vivo; injured; mechanical behavior; novel; pre-clinical; reconstitution; response; scaffold; simulation; skin regeneration; success; tissue reconstruction; tissue regeneration; tissue support frame

Regenerative medicine approaches for the reconstitution of missing or injured tissues and organs involves the use of scaffolds, cells, and bioactive molecules. The use of biologic scaffolds seeded with cells is a common approach and several applications have been successfully translated to clinical medicine including lower urinary tract, gastrointestinal tract, musculotendinous, and dermal skin regeneration. The principles that guide tissue remodeling and regeneration are only partially understood but the influence of biomechanical loading upon the remodeling process is accepted as an important variable. However, there is an almost complete absence of systematic, quantitative studies to determine the effect of this controllable factor upon tissue remodeling, especially tissues with a smooth muscle wall component. The present proposal seeks support to conduct a quantitative, hypothesis driven study that determines the effects of mechanical loading upon smooth muscle phenotype in vitro and in vivo and the related changes to the architecture of the scaffold upon which they are seeded. A biologic scaffold derived from the extracellular matrix (ECM) of a porcine urinary bladder will be seeded with smooth muscle cells derived from different sources: the vascular wall, urinary bladder, and esophagus. The influence of those organ specific mechanical loading regimens upon the remodeling process and the ability to modulate the remodeling process by changing the mechanical loading pattern will be investigated. Two specific aims are described in which: 1) ECM seeded with the three different types of smooth muscle will be subjected to carefully selected mechanical loading regimens and the effect upon cell phenotype and matrix organization will be quantitatively evaluated and 2) two smooth muscle cells types will be evaluated upon ECM used within an organ culture model (rat bladder wall) to evaluate the effect of cellular and ECM remodeling when adjacent normal tissue cells are present. An experienced interdisciplinary team consisting of biomechanical engineers, tissue engineers, physicians, and pathologists has been assembled to conduct these studies. Two consultants, including a leader in the field of regenerative medicine and a statistician, will support this effort. A timeline for completion of these studies, hypotheses to drive the specific aims, alternative approaches for completion of the work, and quantitative criteria for success are provided.

重建缺失或受伤的组织和器官的再生医学方法涉及使用支架、细胞和生物活性分子。使用接种细胞的生物支架是一种常见的方法，并且一些应用已成功转化为临床医学，包括下尿路、胃肠道、肌腱和真皮皮肤再生。指导组织重塑和再生的原理仅被部分理解，但生物力学负荷对重塑过程的影响被认为是一个重要变量。然而，几乎完全缺乏系统的定量研究来确定这种可控因素对组织重塑的影响，特别是具有平滑肌壁成分的组织。本提案寻求支持进行一项定量的、假设驱动的研究，以确定机械负荷对体外和体内平滑肌表型的影响，以及它们所种植的支架结构的相关变化。来自猪膀胱细胞外基质 (ECM) 的生物支架将接种来自不同来源的平滑肌细胞：血管壁、膀胱和食道。将研究这些器官特异性机械负荷方案对重塑过程的影响以及通过改变机械负荷模式来调节重塑过程的能力。描述了两个具体目标，其中：1) 接种三种不同类型平滑肌的 ECM 将接受精心选择的机械加载方案，并且将定量评估对细胞表型和基质组织的影响；2) 两种平滑肌细胞类型将根据器官培养模型（大鼠膀胱壁）中使用的 ECM 进行评估，以评估当存在相邻正常组织细胞时细胞和 ECM 重塑的效果。由生物力学工程师、组织工程师、医生和病理学家组成的经验丰富的跨学科团队已经组建起来进行这些研究。两名顾问，包括一名再生医学领域的领导者和一名统计学家，将支持这项工作。提供了完成这些研究的时间表、推动具体目标的假设、完成工作的替代方法以及成功的定量标准。

项目成果

Strain history and TGF-β1 induce urinary bladder wall smooth muscle remodeling and elastogenesis.

• DOI: 10.1007/s10237-011-0298-y
• 发表时间: 2012-01
• 期刊: BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
• 影响因子: 3.5
• 作者: Heise, Rebecca L.;Parekh, Aron;Joyce, Erinn M.;Chancellor, Michael B.;Sacks, Michael S.
• 通讯作者: Sacks, Michael S.

Phenotypic changes in cultured smooth muscle cells: limitation or opportunity for tissue engineering of hollow organs?

• DOI: 10.1002/term.451
• 发表时间: 2012-07
• 期刊: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
• 影响因子: 3.3
• 作者: Huber, Alexander;Badylak, Stephen F.
• 通讯作者: Badylak, Stephen F.