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可用于控制成人间充质干细胞三维行为的新型动态水凝胶，并将教育整合到大学、地方和国际层面的研究计划中。这项工作的前提是，通过开发新型生物材料获得的对细胞-环境相互作用的进一步基础知识和后续控制，将有助于推动该领域的发展。考虑到这一点，这项拟议工作的主导假设是，具有空间可控性质的水凝胶可以用于引导和定义细胞在三维中的扩散、迁移和表型，从而实现复杂组织的工程。该研究计划的目标是：(1)合成新型多功能大分子单体，利用连续的交联法形成具有空间可控性质的网络；(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)通过空间可控的交联密度来评估水凝胶中对细胞分化的控制。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，因此这项工作代表了这些领域的智力进步。拟议的教育活动被纳入这项研究，包括在实验室和课堂上对研究生和本科生进行教育，向当地一所高中进行宣传，以及向非洲的一所大学进行国际宣传。具体组成部分包括：(1)继续让学生参与，重点是妇女和少数族裔学生，参与首席研究人员的实验室，并将“动手”学习的实验室组成部分纳入生物材料课程，该课程教授给高年级本科生和研究生；(2)通过开发一门“世界材料”课程，向费城学校的学生宣传，让高中生接触材料科学和生物材料，以鼓励在这些领域的职业；以及(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包含的主题，并邀请来自非洲的学生在夏季几个月加入宾夕法尼亚大学的首席研究人员实验室。

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.