A Developmentally-Based Tissue Engineering Approach to Improve Tendon Repair

一种基于发育的组织工程方法来改善肌腱修复

• 批准号: 7991696
• 负责人: DAVID L BUTLER
• 金额: $ 15.7万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-10 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991696
• 关键词: Area; Autologous Transplantation; Biochemical; Biological; Biomechanics; Biomedical Engineering; Businesses; Case Study; Cells; Charge; Clinical; Collaborations; Data; Development; Developmental Biology; Devices; Doctor of Philosophy; Education; Engineering; Entrepreneurship; Ethnography; Faculty; Funding; Future; Goals; Grant; Growth Factor; Healed; Histology; Human; In Vitro; Interview; Knee; Laboratories; Ligaments; Longevity; Medical Device; Mesenchymal Stem Cells; Modeling; Ohio; Operating Rooms; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patients; Phenotype; Procedures; Process; Public Health; Reconstructive Surgical Procedures; Recruitment Activity; Research; Research Personnel; Science; Secure; Shoulder; Site; Solutions; Specific qualifier value; Sports Medicine; Students; Surgeon; Surveys; System; Technology; Tendon structure; Testing; Tissue Engineering; Tissue Grafts; Translating; United States National Institutes of Health; Universities; Work; base; bone; commercialization; design; engineering design; experience; fundamental research; graduate student; graft function; healing; implantation; improved; in vitro testing; in vivo; injured; innovation; instrumentation; meetings; novel; novel strategies; preclinical study; professor; programs; public health relevance; reconstruction; repaired; research and development; sample fixation; scaffold; soft tissue; success

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.

描述（由申请人提供）：这份为期一年的 BIRT 研究补充极大地扩大了我们最近资助的 5 年期 NIH 生物工程研究合作基金 (AR56943-01) 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转化应用。此次合作由辛辛那提大学生物医学工程系的四名教员（David Butler 博士和 Jason Shearn 博士，分别为组织工程师、教授和助理教授；Mary Beth Privitera，设计硕士，工业设计师、副教授和独立研究员；Scott Wampler，B.S.，企业家和最近聘用的助理教授）和 Heather 共同完成。 鲍威尔博士，俄亥俄州立大学材料科学与工程助理教授。教师团队将与我们的 TE/DB 团队合作，为三个由工业设计、商业和生物医学工程领域的本科生和研究生组成的团队提供建议，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。这些装置将由接种在注入生长因子的支架中的间充质干细胞（MSC）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介或问题陈述。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）小组，并在手术室观察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以及将组织工程增强从实验室转化为患者时需要克服的障碍。在剩下的九个月里，核心团队将直接监管两个本科生BME实施团队，一个在我们系的“研究聚焦”轨道，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，这些解决方案可以在体外和手术中的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 团队将专注于软组织移植增强过程中的人为因素挑战（例如处理、固定和植入）。这些设计自然会遵循我们的 BRP 研究，但拥有一个涵盖从台式到床边的更全面的 BIRT 团队。该团队将在未来的 R01 应用中扩展和改进该模型，作为招募优秀本科生进入加州大学生物医学工程研究生项目的渠道，并代表许多其他组织工程应用的案例研究。 公共健康相关性：拟议的研究与公共健康相关，因为外科医生正在寻找提高患者肌腱和韧带移植物的质量和寿命的方法。用自体间充质干细胞接种的生长因子注入的构建体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。