CAREER: Ultrasound-Assisted Biofabrication Of Biomimetic Soft Tissue Constructs With Aligned Fiber Organization

该学院早期职业发展(Career)奖项目涉及使用超声波原理来帮助使用高度组织化的纤维作为增强材料对功能组织进行生物打印，从而提供更强大的功能生物制造组织。这已经被认为是现有生物打印应用的一个严重的技术限制，并具有深远的影响。也许最直接的是生产用于软组织重建手术的支架，这种支架具有更好的机械性能。长期应用意义重大，范围从用于药物评估的结构到替代器官。国际生物研究所的教育和推广计划包括开发生物制造课程和一个集中的基于网络的生物制造知识资源，以及向K-12学生和更广泛的生物打印社区进行广泛的推广。具体地说，PI将为高中生开发一个生物设计和制造夏季研讨会，并与北卡罗来纳州科学博物馆合作。在使用细胞注入仿生学的添加剂制造中使用驻留超声波会导致增强纤维的取向。利用PI在生物医学设计和制造方面的专业知识、多学科合作和实验室能力，该项目将产生关于3D封装细胞、纳米纤维和细胞分泌的细胞外基质(ECM)的超声波操作中基本材料-工艺-结构-功能相互作用的新知识。研究结果将证实，水凝胶中排列的聚合物纳米纤维是否能更好地引导纤维状细胞外基质沿排列轨迹形成，而不是单独排列的包裹细胞(没有纳米纤维)。经过验证的分析和经验模型将提供UAB参数与功能关键细胞和ECM反应之间相互关系的多变量映射。首次实现了具有仿生ECM组织结构的人前交叉韧带(ACL)和纤维环组织的3D生物打印。

This Faculty Early Career Development (CAREER) award project involves the use of ultrasound principles to aid in bioprinting of functional tissues with highly organized fibers as reinforcement, thereby providing for stronger functional biomanufactured tissue. This has been recognized as a serious technical limitation of existing bioprinting applications, and has far-reaching impacts. Perhaps the most immediate is the production of scaffolds for soft tissue reconstruction surgeries where the scaffold has improved mechanical properties. Long-term applications are significant and range from constructs for drug evaluation to replacement organs. The PI's education and outreach plan includes development of courses on biofabrication as well as a centralized biofabrication web-based knowledge resource, as well as extensive outreach to K-12 students and the broader bioprinting community. Specifically, the PI will develop a Bio-Design and Manufacturing summer workshop for high school students and collaborations with the North Carolina Science Museum. The use of a standing ultrasonic wave in additive manufacturing with cell-infused bionics leads to orientation in reinforcing fibers. Leveraging the PI's expertise in biomedical design and manufacturing, multidisciplinary collaborations, and lab capabilities, this project will generate new knowledge about fundamental material-process-structure-function interactions in the ultrasonic manipulation of 3D encapsulated cells, nanofibers and cell-secreted extracellular matrix (ECM). The outcomes will confirm if aligned polymer nanofibers within a hydrogel can guide fibrous ECM formation along their alignment trajectory better than aligned encapsulated cells alone (without nanofibers). The validated analytical and empirical models will provide a multivariate mapping of UAB parameter interrelationships with functionally-critical cellular and ECM responses. For the first time, the 3D-bioprinting of human anterior cruciate ligament (ACL) and annulus fibrosus tissue constructs with biomimetic ECM organization will be achieved.