A Developmentally-Based Tissue Engineering Approach to Improve Tendon Repair

描述(由申请人提供)：这项为期一年的BIRT研究补充资料，通过探索基于组织工程和发育生物学(TE/DB)基础研究的肌腱和韧带修复的翻译应用，极大地扩大了我们最近资助的为期5年的NIH生物工程研究伙伴关系补助金(AR56943-01)的影响。这项合作是由辛辛那提大学生物医学工程系的四名教员(组织工程师、教授和助理教授大卫·巴特勒博士和杰森·谢恩博士；工业设计师、副教授和独立调查员玛丽·贝丝·普里维特拉M.Design；以及企业家和最近聘用的助理教授斯科特·万普勒B.S.)和俄亥俄州立大学材料科学与工程助理教授希瑟·鲍威尔博士共同完成的。与我们的TE/DB小组合作，教师团队将建议工业设计、商业和生物医学工程的三个本科生和研究生团队设计和实施用于肌腱和韧带自体移植修复的生物增强结构(BAC)的商业化。这些装置将由种植在注入生长因子的支架中的间充质干细胞(MSCs)组成。核心团队(两名生物医学工程研究生加上两名工业设计和商业合作教育本科生)将在前三个月为设计这些新型生物制剂制定创新简报或问题陈述。该团队将调查该领域的思想领袖，然后采访我们这组运动医学、膝盖和肩部外科医生(BRP的顾问)，并在手术室观察重建肌腱和韧带的手术。这些经验将使这个团队能够确定成功的设计标准，以及在将组织工程假体从实验室转移到患者身上需要克服的障碍。在剩下的9个月里，核心团队将直接监督两个本科生BME实施团队，一个在我们系的《聚焦研究》赛道，另一个在我们的《医疗器械创新创业计划》(MDIEP)。这三个团队将负责开发可行的解决方案，这些方案既可以在体外进行测试，也可以在手术时在兔自体肌腱移植模型中进行测试。研究团队将专注于拟议设计中的生物和生物力学问题，而MDIEP团队将专注于提供软组织移植物增强手术中的人为因素挑战(例如，处理、固定和植入)。设计自然将遵循我们的BRP研究，但有一个更全面的BIRT团队，从桌面到床边。该团队将在未来的R01应用中对该模型进行扩展和改进，作为我们加州大学研究生生物医学工程项目招收有才华的本科生的渠道，并为许多其他组织工程应用提供案例研究。 公共卫生相关性：拟议的研究与公共健康相关，因为外科医生正在寻找方法来提高他们患者的肌腱和韧带移植物的质量和寿命。用种植有自体间充质干细胞的生长因子注入的构建物来增强这些移植物可以改善移植物的完整性和功能。开发一种将这些实验室产生的结构转化为临床有用产品的方法，可以在软组织重建手术中找到广泛的用途。

DESCRIPTION (provided by applicant): This one-year BIRT research supplement dramatically expands the impact of our recently-funded 5-year NIH Bioengineering Research Partnership Grant (AR56943-01) by exploring translational applications for tendon and ligament repair based on fundamental research at the interface of tissue engineering and developmental biology (TE/DB). The collaboration is among four faculty in the Department of Biomedical Engineering at the University of Cincinnati (David Butler, PhD, and Jason Shearn, PhD, tissue engineers and Professor and Assistant Professor, respectively; Mary Beth Privitera, M. Design, an industrial designer, Associate Professor and independent investigator; and Scott Wampler, B.S., an entrepreneur and recently-hired Assistant Professor) and Heather Powell, PhD, Assistant Professor of Materials Science and Engineering at the Ohio State University. Working with our TE/DB group, the faculty team will advise three teams of undergraduate and graduate students in industrial design, business, and biomedical engineering to design and implement the commercialization of biological augmentation constructs (BACs) for tendon and ligament autograft repair. These devices will be composed of mesenchymal stem cells (MSCs) seeded in growth factor-infused scaffolds. The core team (two graduate students in biomedical engineering plus two undergraduate cooperative education students in industrial design and business) will spend the first three months developing an innovation brief or problem statement for designing these novel biologics. The team will survey thought leaders in the field and then interview our group of sports medicine knee and shoulder surgeons (consultants on the BRP) and observe surgeries to reconstruct tendons and ligaments in the operating room. These experiences will enable this team to identify design criteria for success and impediments to be overcome in translating tissue engineered augmentations from the laboratory to the patient. In the remaining nine months, the core team will directly supervise two undergraduate BME implementation teams, one in our department's "Research Focused" track and the other in our "Medical Device Innovation and Entrepreneurship Program" (MDIEP). The three teams will be charged with developing viable solutions that can be tested both in vitro and in a rabbit tendon autograft model at surgery. The Research team will focus on biological and biomechanical issues in the proposed designs while the MDIEP team will concentrate on human factors challenges (e.g. handling, fixation, and implantation) in delivering soft tissue graft augmentations. The designs will naturally follow from our BRP research, but with a more comprehensive BIRT team spanning from the benchtop to the bedside. The model will be expanded and improved in future R01 applications by the team, serve as a conduit for recruiting talented undergraduate students into our graduate biomedical engineering program at UC, and represent a case study for many other tissue engineering applications. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health in that surgeons are seeking ways to enhance the quality and longevity of tendon and ligaments grafts in their patients. Augmentation of these grafts with growth factor-infused constructs seeded with autogolous mesenchymal stem cells could improve the integrity and function of these grafts. Developing an approach for translating these laboratory-generated constructs into clinically useful products could find broad utility in soft tissue reconstructive surgery.