A Developmentally-Based Tissue Engineering Approach to Improve Tendon Repair

描述（由申请人提供）：这一为期一年的BIRT研究补充大大扩大了我们最近资助的5年NIH生物工程研究合作伙伴基金（AR 56943 -01）的影响，通过探索基于组织工程和发育生物学（TE/DB）界面基础研究的肌腱和韧带修复的翻译应用。这项合作是在辛辛那提大学生物医学工程系的四名教师之间进行的（大卫巴特勒博士和杰森希恩博士，分别是组织工程师和教授和助理教授;玛丽贝丝普里维特拉，M。设计，工业设计师，副教授和独立调查员;和斯科特Wampler，B.S.，企业家和最近聘请的助理教授）和石楠鲍威尔，博士，材料科学与工程助理教授在俄亥俄州州立大学。与我们的TE/DB团队合作，教师团队将为工业设计，商业和生物医学工程的三个本科生和研究生团队提供建议，以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。这些设备将由间充质干细胞（MSC）接种在生长因子注入支架。核心团队（两名生物医学工程专业的研究生和两名工业设计和商业专业的本科合作教育学生）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，然后采访我们的运动医学膝关节和肩关节外科医生（BRP顾问），并观察手术室中重建肌腱和韧带的手术。这些经验将使该团队能够确定成功的设计标准和将组织工程扩增从实验室转化到患者中所要克服的障碍。在剩下的九个月里，核心团队将直接监督两个本科生BME实施团队，一个在我们部门的“研究重点”轨道，另一个在我们的“医疗器械创新和创业计划”（MDIEP）。这三个团队将负责开发可行的解决方案，这些解决方案可以在体外和手术中的兔肌腱自体移植模型中进行测试。研究团队将专注于拟定设计中的生物学和生物力学问题，而MDIEP团队将专注于提供软组织移植物增强的人为因素挑战（例如，处理、固定和植入）。这些设计将自然遵循我们的BRP研究，但有一个更全面的BIRT团队，从台式到床边。该模型将在未来的R 01应用中得到扩展和改进，作为招募有才华的本科生进入我们的研究生生物医学工程项目的渠道，并代表许多其他组织工程应用的案例研究。 公共卫生相关性：这项拟议中的研究与公共卫生有关，因为外科医生正在寻求提高患者肌腱和韧带移植物质量和寿命的方法。用自体间充质干细胞接种的生长因子灌注结构增强这些移植物可以改善这些移植物的完整性和功能。开发一种将这些实验室生成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.