Ultrasound As a Physical Force for Enhanced Scaffold-Based Bone Repair

超声波作为增强支架骨修复的物理力量

基本信息

批准号：
8638411
负责人：
Yusuf M Khan
金额：
$ 16.89万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-17 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8638411
关键词：
3-Dimensional Acoustics Behavior Belief Bone Marrow Bone Regeneration Bone Tissue Calvaria Cells Ceramics Clinical Collagen Connecticut Defect Development Encapsulated Engineering Extracellular Matrix Fracture Fracture Healing Gel Gene Expression Goals Healed Hour Hydrogels Implant In Vitro Intention Laboratories Marrow Measurable Measures Mechanical Stimulation Mechanics Modeling Molecular Osteoblasts Output Physiologic pulse Polymers Polystyrenes Process Property Proteins Radiation Rattus Regimen Research Research Proposals Scientist Skin Staging Stem cells System Technology Time Tissue Engineering Transducers Ultrasonography Universities Up-Regulation Viscosity Work base bone cell behavior clinical application clinically relevant design fluid flow healing implantation in vivo novel novel strategies osteoblast differentiation osteoprogenitor cell public health relevance radiation effect repaired response scaffold stem cell differentiation tissue culture viscoelasticity

项目摘要

Non-invasive, low-intensity pulsed ultrasound has been shown to be effective for transdermal treatment of fresh fractures (38% reduction in clinical and radiographic healing time) and fracture nonunions, while less effective for large scale segmental defects. The mechanism through which LIPUS acts is poorly understood, which has weakened enthusiasm for widespread clinical use. Although the exact mechanism is not known, in vitro cell studies have shown that osteoblasts respond to LIPUS exposure much the same as they respond to various forms of mechanical loading, suggesting that LIPUS may impart a physical, acoustic radiation force on cells to stimulate a response. Scaffold-based tissue engineering has also been proposed for the repair of fractures but, unlike LIPUS, large-scale fracture non-unions and has been used clinically to a limited extent. Each approach has its merits but to date have not been combined in a synergistic way; that is, LIPUS has not been applied to implanted deformable hydrogels for bone defect repair. The goal of this proposal is to combine LIPUS generated acoustic radiation force with hydrogel-based tissue engineering with the belief that both approaches together will enhance repair over either approach alone. Using LIPUS-generated force capable of imparting physical forces on cells, it is our intention to design hydrogel scaffolds that are 1) able to deliver encapsulated viable cells in vivo, 2) be physically deflected by LIPUS generated acoustic radiation force after implantation and during the healing process and 3) transfer the physical force from the hydrogel to encapsulated cells to stimulate more rapid bone repair. The objectives of the present research are 1) to evaluate the effect of LIPUS-induced acoustic radiation force on rat marrow derived stem cells using three different acoustic radiation forces, 2) to evaluate the effect of radiation force on cells encapsulated in collagen hydrogels of varying viscoelasticities to determine the relationship between applied force and hydrogel viscosity on cell behavior, and 3) to use acoustic force applied to hydrogels that have been loaded with cells and implanted in rat calvarial defects. Implanted hydrogels containing cells will be loaded transdermally using LIPUS induced acoustic radiation force after implantation into calvarial defects and during the healing process. It is anticipated that the parameters defined in the in vitro studies will result in enhanced in vivo calvarial defect healing in hydrogels under acoustic radiation force when compared to either hydrogels alone or acoustic radiation force alone.

非侵入性、低强度脉冲超声波已被证明可有效用于透皮治疗新鲜骨折（临床和放射学愈合时间减少 38%）和骨折不愈合，同时减少对大面积节段性缺损有效。 LIPUS 的作用机制尚不清楚，这削弱了临床广泛使用的热情。虽然具体机制尚不清楚，但在体外细胞研究表明，成骨细胞对 LIPUS 暴露的反应与它们对 LIPUS 暴露的反应大致相同。各种形式的机械载荷，表明 LIPUS 可能会向物体施加物理声辐射力细胞刺激反应。基于支架的组织工程也被提议用于修复但与 LIPUS 不同的是，它可以治疗大面积骨折不愈合，并且在临床上的应用程度有限。每种方法都有其优点，但迄今为止尚未以协同方式组合起来；也就是说，LIPUS 没有已应用于植入可变形水凝胶以修复骨缺损。该提案的目标是结合 LIPUS 通过基于水凝胶的组织工程产生声辐射力，相信两者与单独使用任何一种方法相比，联合使用这些方法将增强修复效果。使用 LIPUS 产生的力能够对细胞施加物理力，我们的目的是设计水凝胶支架，其 1）能够传递体内封装的活细胞，2) 被 LIPUS 产生的声辐射力物理偏转植入和愈合过程中以及3）将物理力从水凝胶转移到封装细胞刺激更快速的骨修复。本研究的目的是 1) 评估 LIPUS 引起的声辐射力的影响使用三种不同的声辐射力对大鼠骨髓干细胞进行实验，2) 评估对封装在不同粘弹性胶原水凝胶中的细胞施加辐射力，以确定施加的力和水凝胶粘度对细胞行为的关系，以及 3) 使用施加的声力已装载细胞并植入大鼠颅骨缺损的水凝胶。植入水凝胶植入后，将使用 LIPUS 诱导的声辐射力透皮加载含有细胞的细胞颅骨缺损和愈合过程中。预计体外定义的参数研究将导致水凝胶在声辐射力作用下增强体内颅骨缺损愈合与单独的水凝胶或单独的声辐射力相比。