Cell-Responsive Biomaterials as Tissue Engineering Scaffolds

该奖项由德克萨斯工程实验站(TAMU)材料研究部的生物材料计划颁发，旨在开发一系列仿胶原聚氨酯，将合成弹性体的强度和可调性与天然胶原蛋白的细胞响应性降解结合在一起。当传统的移植无法获得或失败时，组织工程学已成为韧带重建的一种有前途的替代方案。韧带组织工程策略的成功依赖于1)在重建过程中保持足够的力学性能以稳定关节的结构；以及2)新组织接受适当水平的负荷以定向胶原组织/排列。预测和调整当前合成生物材料的非特异性水解仍然是困难的；然而，天然材料受到大规模生产、可变性或缺乏韧带应用所需的拉伸性能的限制。需要新的生物材料来满足韧带修复所需的复杂设计标准。通过将支架降解的控制让给细胞，支架将以最快的速度降解，从而促进组织的形成和组织。拟议的研究将提供在组织工程支架中使用这些生物材料所需的合成路线和预测的结构-性质关系。此外，还将对这些新型聚氨酯进行系统的研究，以描述降解和机械载荷对材料性能的单独影响。预测支架的拉伸性能在降解过程中如何变化以及这些过程如何受载荷的影响是合理设计韧带支架的关键。在更大的范围内，本研究开发的结构模型和方法也将适用于其他临床专科，在这些专科中，生物降解显示出改善患者护理的希望(例如，心血管组织工程、可生物降解支架、固定装置等)。通过这一奖项，PI将研究使用胶原型聚氨酯所需的合成路线和预测结构-性能关系，这种聚氨酯将合成聚氨酯的强度和可调性与天然胶原蛋白的细胞响应降解结合在一起。在组织工程支架中。拟议的研究将被用作教育和培训工具，以(1)增加对令人兴奋的生物医学研究的接触，以及(2)为学生从事科学和工程职业做好准备。此外，PI计划扩大本科生的参与范围，从历史上的黑人大学草原景观农工大学招募这些学生参加暑期实习。拟议研究的跨学科和多尺度性质将提供一个严格的培训基础，为本科生和研究生在学术界、国家实验室或行业的职业生涯做准备。该研究项目将用于培养学生的批判性思维，并使学生掌握最先进的化学、聚合物科学和工程实验技能。此外，报告、论文、手稿起草、每周小组会议上的发言以及在区域和国家会议上发言的机会将培养有效的沟通技能。最后，这项研究得出的原则和结果将被纳入到PI教授的课程中，以教育学生并鼓励他们对生物材料研究的兴趣。

This award by the Biomaterials program in the Division of Materials Research to the Texas Engineering Experiment Station (TAMU) is to develop a series of collagen-mimetic polyurethanes that combine the strength and tunability of synthetic elastomers with the cell-responsive degradation of native collagen. Tissue engineering has emerged as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Success of ligament tissue engineering strategies depend upon 1) the construct retaining sufficient mechanical properties to stabilize the joint throughout remodeling; and 2) the new tissue receiving the appropriate level of load for directed collagenous organization/alignment. It continues to be difficult to both predict and tailor the non-specific hydrolysis of current synthetic biomaterials; whereas, natural materials are limited by mass-production, variability, or lack the tensile properties necessary for ligament applications. New biomaterials are needed that can meet the complex design criteria necessary for ligament repair. By yielding control of scaffold degradation to the cell, the scaffold will degrade at a rate that best promotes tissue formation and organization. The proposed studies will provide the synthetic routes and predictive structure-property relationships necessary to use these biomaterials in tissue engineering scaffolds. In addition, systematic study of these novel polyurethanes will be carried out to delineate individual effects of degradation and mechanical load on material properties. The ability to predict how the tensile properties of a scaffold change during degradation and how these processes are influenced by loading is critical in the rational design of ligament scaffolds. On a grander scale, the structural models and methodology developed in this research will also be applicable to other clinical specialties in which biodegradation shows promise in improving patient care (e.g. cardiovascular tissue engineering, biodegradable stents, fixation devices, etc.). By this award, the PI will study the synthetic routes and predictive structure-property relationships necessary to use collagen-like polyurethanes that combine the strength and tunability of synthetic polyurethane with the cell-responsive degradation of native collagen. in tissue engineering scaffolds. The proposed research will be used as an educational and training tool to (1) increase the exposure to exciting biomedical research, and (2) prepare students to pursue careers in science and engineering. In addition, the PI plan to broaden the participation of undergraduate students by recruiting these students for summer internships from Prairie View A&M University, a Historically Black University. The interdisciplinary and multi-scale nature of the proposed research will provide a rigorous training ground to prepare both undergraduate and graduate students for careers in academia, national laboratories, or industry. The research program will be used to foster critical thinking and equip students with state-of-the-art experimental skills in chemistry, polymer science and engineering. In addition, reports, theses, manuscript drafting, presentations at weekly group meetings, and opportunities to present at regional and national meetings will foster effective communication skills. Finally, the principles and results coming out of this research will be incorporated into courses taught by the PI to educate students and encourage interest in biomaterial research.