EAGER: Transdermal Acoustic Radiation Force for Bone Regeneration

EAGER：透皮声辐射力促进骨再生

• 批准号: 1752915
• 负责人: Yusuf Khan
• 金额: $ 20万
• 依托单位: University of Connecticut Health Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1752915&HistoricalAwards=false
• 关键词: EAGER; Transdermal; Acoustic; Radiation; Force

Bone grafts are commonly used to treat bone defects and enhance fracture repair. Bone tissue grafts taken from the patient -- autografts -- are the gold standard, but require a second surgery and are limited in volume. Allografts, taken from a cadaver, have a fairly high failure rate after 10 years. Tissue engineered bone grafts hold promise, but have seen limited success due to the need of bone cells to see mechanical loading during the development and healing process in order to grow properly. This research project investigates the combination of hydrogels to encapsulate bone cells with low intensity pulsed ultrasound to provide controlled mechanical stimulation in order to enhance bone tissue development. The optimum combination of hydrogel stiffness and acoustic radiation force level is being determined first, and then the system is being tested in mice to determine whether or not it is effective for treating a bony defect when the ultrasound is applied through the skin. The project integrates students from high school through graduate and medical school into the research effort and introduces new course content into a biomaterials class. The objectives of this research project are to evaluate the impact in vitro of RGD-modified alginate hydrogel stiffness and low-intensity pulsed ultrasound derived acoustic radiation force on encapsulated osteoblast behavior and to assess the efficacy, in vivo, of transdermally applied acoustic radiation force on osteoblasts encapsulated in an RGD-modified alginate hydrogel and implanted into a mouse cranial defect. Combinations of hydrogel stiffness and acoustic radiation force levels are being investigated to determine the optimum levels for upregulating phenotypic markers and mineralization of the encapsulated osteoblasts. The optimum system is then being utilized in a mouse cranial defect model, with ultrasound force applied daily for 20 minutes a four-week period. The healing of the construct is being evaluated through histology and histomorphometry.

骨移植通常用于治疗骨缺损和加强骨折修复。从患者身上取出的骨组织移植--自体移植--是黄金标准，但需要进行第二次手术，而且体积有限。取自身体的同种异体移植物在10年后的失败率相当高。组织工程化骨移植前景看好，但由于骨细胞在发育和愈合过程中需要看到机械载荷才能正常生长，因此成功的情况有限。本研究项目研究了将水凝胶与低强度脉冲超声结合起来包裹骨细胞，以提供受控的机械刺激，以促进骨组织的发育。首先确定水凝胶硬度和声辐射力水平的最佳组合，然后在小鼠身上测试该系统，以确定当超声波通过皮肤施加时，该系统是否对治疗骨缺陷有效。该项目将从高中到研究生和医学院的学生纳入研究工作，并将新的课程内容引入生物材料课程。本研究项目的目的是评估RGD修饰的海藻酸盐水凝胶的硬度和低强度脉冲超声产生的声辐射力在体外对包裹的成骨细胞行为的影响，并在体内评估经皮加声辐射力对包裹在RGD修饰的海藻酸盐水凝胶中的成骨细胞的有效性并将其植入小鼠颅骨缺损中。水凝胶硬度和声辐射力水平的组合正在研究中，以确定上调包膜成骨细胞表型标志物和矿化的最佳水平。然后，将最优系统用于小鼠颅骨缺损模型，在四周内每天施加20分钟的超声力。通过组织学和组织形态计量学对构建物的愈合情况进行评估。