The 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.
