CAREER: Spatially Controlled Cellular Behavior in 3D Hydrogels: An Integrated Research, Teaching, and Outreach Approach

该项目的总体目标是设计和开发新的动态水凝胶，可用于在三维空间上控制成体间充质干细胞的行为，并将教育纳入大学，地方和国际层面的研究计划。这项工作的前提是，通过开发新型生物材料获得的进一步的基础知识和随后对细胞-环境相互作用的控制，将有助于推进该领域的发展。考虑到这一点，所提出的工作的主要假设是，具有空间控制特性的水凝胶可用于指导和定义三维的细胞扩散、迁移和表型，从而实现复杂组织的工程。本研究计划的目标是：(1)利用顺序交联程序合成新型多功能大分子，形成具有空间控制特性的网络；(2)利用合成的水凝胶来控制间充质干细胞的扩散和迁移，并建立结构/结果关系；(3)通过空间控制交联密度来评估水凝胶对细胞分化的控制。拟议的研究是多学科的，涵盖了从聚合物科学到细胞生物学的许多领域。可用材料的限制可能阻碍了间充质干细胞生物学和组织再生领域的重大进展，因此这项工作在这些领域提出了一个智力上的进步。拟议的教育活动被整合到这项研究中，包括在实验室和课堂上对研究生和本科生的教育，向当地一所高中的推广，以及向非洲一所大学的国际推广。具体的组成部分包括：(1)学生继续参与，重点是女性和少数民族学生，在首席研究员的实验室中，并将“动手”学习的实验室组成部分整合到面向高年级本科生和研究生的生物材料课程中；(2)通过开设“世界上的材料”课程与费城学校的学生进行接触，让高中生接触材料科学和生物材料，鼓励他们在这些领域从事职业；(3)前往非洲加纳，对学生进行生物医学工程领域的教育，这是目前任何课程都没有涉及的主题，并邀请非洲学生在夏季加入宾夕法尼亚大学首席研究员的实验室。

0845472BurdickThe overall objective of this project is to design and develop novel dynamic hydrogels that can be used to control adult mesenchymal stem cell behavior in 3-dimensions, as well as to integrate education into the research plan at the university, local, and international levels. The premise of the work is that further fundamental knowledge and subsequent control of the cell-environment interactions, gained through the development of novel biomaterials, will help advance the field. With this in mind, the governing hypothesis of the proposed work is that hydrogels with spatially controlled properties can be used to direct and define cellular spreading, migration, and phenotypes in 3-dimensions, towards the engineering of complex tissues. The objectives of the research plan are: (1) to synthesize novel multifunctional macromers that form networks with spatially controlled properties using sequential crosslinking procedures, (2) to utilize the synthesized hydrogels to control the spreading and migration of mesenchymal stem cells and develop structure/outcome relationships, and (3) to assess control over cellular differentiation in hydrogels through spatially controlled crosslinking density. The proposed research is multidisciplinary and covers many fields from polymer science to cellular biology. Limitations in available materials may have stalled significant advances in the fields of mesenchymal stem cell biology and tissue regeneration, and thus this work presents an intellectual advance in these areas. The proposed educational activities are integrated within this research and include education to graduate students and undergraduate students in the laboratory and classroom, outreach to a local high school, and international outreach to a university in Africa. The specific components include: (1) continued involvement of students, emphasizing women and minority students, in the principal investigator's laboratory and integration of a laboratory component for "hands-on" learning into a course on Biomaterials that is taught to upper-level undergraduate and graduate students; (2) outreach to students in Philadelphia schools through the development of a course on 'Materials in the World' that gives high school students exposure to material science and biomaterials to encourage careers in these fields; and (3) travel to Ghana, Africa to educate students in the area of biomedical engineering, a topic that is not encompassed into any current curriculum, and invitations to students from Africa to join the principal investigator's laboratory at Penn during the summer months.