BME PhD Defense Seminar: Carlos Sevilla
The Role of Extracellular Matrix Fibronectin and Collagen in Cell Proliferation and Cellular Self-Assembly
Supervised by Dr. Denise Hocking & Dr. Diane Dalecki
Biomimetic approaches in tissue engineering aim to fabricate tissues and organs by emulating the process of tissue formation in development. Fibronectin is a principal component of the extracellular matrix (ECM) and plays an important role in regulating tissue formation in development. ECM fibronectin can serve a passive role, maintaining tissue structure, or a signaling role, instructing cell behaviors. Understanding how fibronectin transitions from passive to signaling roles may permit the engineering of biomimetic biomaterials that promote tissue and organ formation through inductive and instructive ECM environments. ECM fibronectin function can be regulated by the composition of the surrounding ECM and the organization of ECM fibronectin. The goal of this thesis was to determine how the organization of ECM fibronectin and the composition of the ECM affect cell proliferation and the assembly of cells into 3-dimensional (3D) structures. To investigate the role of fibronectin in tissue formation, a model of self-assembling 3D microtissues was developed that combined compliant, low adhesive polymerized collagen I substrates with the cell-mediated assembly of fibronectin matrix fibrils. The data presented in this thesis demonstrate the existence of two functional forms of ECM fibronectin: a growth-promoting collagen-associated fibronectin matrix and a pericellular fibronectin matrix capable of providing structural support for assembly of cells into 3D structures. Thus, the data presented in this thesis demonstrate that the composition and organization of the ECM can be used as instructive signals in the formation of tissues and organs using biomimetic tissue engineering approaches.