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

非侵入性、低强度脉冲超声已被证明是有效的经皮治疗 新鲜骨折(临床和放射学愈合时间缩短38%)和骨折不愈合，但较少 对大规模节段性缺陷有效。LIPUS的行动机制鲜为人知， 这削弱了人们对广泛临床应用的热情。虽然确切的机制尚不清楚，但在 体外细胞研究表明，成骨细胞对LIPUS的反应与它们对 各种形式的机械载荷，表明LIPUS可能会将物理、声辐射力施加到 刺激反应的细胞。基于支架的组织工程也被提出用于修复 但与LIPUS不同的是，大范围骨折不愈合，临床应用有限。 每种方法都有各自的优点，但到目前为止还没有以协同的方式结合起来；也就是说，LIPUS还没有 已被应用于植入型可变形水凝胶修复骨缺损。这项提议的目标是将 Lipus用基于水凝胶的组织工程产生声辐射力，相信两者都 与单独使用任何一种方法相比，两种方法结合在一起将有助于修复工作。使用LIPUS生成的部队能够 将物理力量赋予细胞，我们的目的是设计能够提供 体内包裹的活细胞，2)LIPUS产生的声辐射力在物理上偏转 植入并在愈合过程中，以及3)将水凝胶的物理力传递到 微囊化细胞能刺激更快的骨修复。 本研究的目的是：1)评估LIPUS诱发的声辐射力的影响 三种不同声辐射力对大鼠骨髓间充质干细胞的影响 不同粘弹性胶原水凝胶包裹细胞的辐射力测定 外力与水凝胶粘度对细胞行为的影响；3)外加声力 到装载细胞并植入大鼠颅骨缺损处的水凝胶。植入水凝胶 含有细胞的细胞将在植入后利用LIPUS诱导的声辐射力经皮加载 进入颅骨缺损区并在愈合过程中。预计在体外实验中定义的参数 研究将导致在体内增强水凝胶在声辐射力下的颅骨缺损愈合 与单独的水凝胶或单独的声辐射力相比。

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.