Development of a Novel Bioinspired Fiber Reinforced Hydrogel that Recapitulates Developmental Processes to Regenerate the Bone-Ligament Interface

该奖项由科罗拉多州立大学材料研究部的生物材料项目授予，旨在研究能够模拟软组织和骨之间天然界面的新型生物材料组织结构。该奖项由化学，生物工程，环境和运输系统部门的生物医学工程项目共同资助。国际科学和工程办公室的全球风险基金项目也支持这一项目。尽管之前已经开发了许多软组织置换结构，但很少关注重建工程化置换软组织和硬骨之间的界面。所提出的组织构造将由用聚己内酯纳米纤维增强的复合水凝胶制备，并接种间充质干细胞（MSC）。为了模拟天然软组织-骨界面的结构，将沿着组织构建体的长度调节生物化学和生物物理学线索，以驱动MSC沿着软骨形成、纤维软骨和韧带途径分化。利用组织移植物的这种设计，在体内植入干细胞后，将通过促进结构的软骨形成引发部分的软骨内骨化来建立骨组织的末端部分。这种方法在提供具有促进中间软组织模板形成的能力的空间分级工程化组织移植物方面是独特和创新的，所述中间软组织模板将响应于局部环境线索而分化成适当的终末期组织表型。这一策略是为了概括发育过程的不同方面，其中所有组织都来自软组织前体，特定的环境线索对确定终末期分化至关重要。关于该项目的教育和培训方面，这项工作将涉及在广泛的创新组织工程和生物材料设计技术方面对研究生和本科生进行培训。与爱尔兰和北方爱尔兰的学生交流也是该项目的一部分。该项目汇集了来自美国、爱尔兰和北方爱尔兰的专家，使用结合材料研究、工程、细胞生物学和生物材料的综合方法来解决日益严重的膝关节损伤相关问题。尽管已经开发了许多用于受伤的软组织结构的替代物，但是这些技术通常不能解决软组织-骨界面。该接口对于整个关节的正常功能是必要的。该项目旨在使用一种新型生物材料结构重建软组织和骨之间的界面，该结构模仿天然界面的结构和功能。除了创新研究外，这笔赠款还将利用外联活动来强调对学生和公众的教育。参加这项研究的研究生和本科生将学习生物和工程技术，并将有机会参加会议，传播研究成果和加强国际合作。这项工作还将提供工程经验，以鼓励他们参与研究的大学预科学生。此外，该项目将与当地的美洲原住民社区互动，鼓励他们的成员参加科学科目。在国家工程师周期间，女童子军团体将参与实验室示范，鼓励年轻女孩对科学和工程感兴趣。最后，研究成果将通过在国家认可的期刊上发表向公众传播。

This award by the Biomaterials program in the Division of Materials Research to Colorado State University is to study novel biomaterial tissue constructs that will be able to mimic the native interface between soft tissue and bone. This award is cofunded by the Biomedical Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. The Global Venture Fund program in the Office of International Science and Engineering is also supporting this project. Although numerous soft-tissue replacement constructs have been developed previously, less attention has been dedicated in recreating the interface between the engineered replacement soft-tissue and the hard bone. The proposed tissue construct will be prepared from a composite hydrogel reinforced with polycaprolactone nanofibers, and seeded by mesenchymal stem cells (MSCs). In order to mimic the structure of native soft tissue-to-bone interface, biochemical and biophysical cues will be modulated along the length of the tissue construct to drive the differentiation of MSCs down the chondrogenic, fibrocartilaginous, and ligamentous pathways. With this design of the tissue graft, the end part of the bone tissue will be established by promoting endochondral ossification of the chondrogenically primed portion of the construct following in vivo implantation of stem cells. This approach is unique and innovative in providing a spatially graded engineered tissue grafts with the capacity to promote the formation of an intermediary soft tissue template, which will differentiate into appropriate end-stage tissue phenotypes in response to local environmental cues. This strategy is to recapitulate different aspects of the developmental process, where all tissues are derived from soft tissue precursors and specific environmental cues are critical to determining end-stage differentiation. With respect to educational and training aspects of the project, this work will involve the training of graduate and undergraduate students in a broad range of innovative tissue engineering and biomaterial design techniques. Student exchanges with Ireland and Northern Ireland are also parts of this project.This project brings together experts from the US, Ireland and Northern Ireland to address a growing problem related to knee injuries using a combined approach that incorporates materials research, engineering, cell biology and biomaterials. Although numerous replacements for injured soft tissue structures have been developed, these techniques typically fail to address the soft tissue-to-bone interface. This interface is necessary for the proper functionality of the entire joint. This project seeks to recreate the interface between soft tissue and bone using a novel biomaterial construct that mimics the structure and function of the native interface. In addition to innovative research, this grant will use outreach activities to emphasize the education of students and the general public. Graduate students and undergraduate students who participate in this research will learn both biological and engineering techniques and will have opportunities to attend conferences to disseminate research and strengthen international collaborations. This work will also provide engineering experience to pre-college students in encouraging their participation in research. Additionally, this project will interact with local Native American communities to encourage their members to participate in science subjects. During National Engineers Week, Girl Scout groups will be involved in lab demonstrations in encouraging younger girls to become interested in science and engineering. Finally, the research will be disseminated to the general public by publishing results in nationally recognized journals.