Design of three-dimensional collagen matrices for cell delivery and guidance in tissue engineering.

摘要

The development of tissue engineering biomaterials that can predictably direct cell response requires understanding the complex interactions between cells and their surrounding extracellular microenvironment. Collagen matrices are extensively used in 3D models of the extracellular matrix (ECM) and as scaffoldings for biomaterial design. It is well known that physical properties of collagen matrices (e.g. fibril density, stiffness) can influence cell behavior. However, the utility and application of collagen matrices is currently limited by inadequate understanding of the parameters which control matrix physical properties and the mechanisms by which they influence cells. The work presented here focuses on identifying how specific design parameters (macromolecular composition, collagen source, and collagen concentration) control 3D collagen matrix physical properties (e.g. polymerization, microstructure, mechanics) and influence resident cell behavior. Addition of a unique glycosaminoglycan component of the ECM, hyaluronan, altered matrix viscoelasticity, but not sufficiently to affect fibroblast response. Collagen source (e.g. different purification, tissue origin) was found to control matrix microstructure-mechanics relationships and profoundly alter matrix physical properties. Finally, an in vivo transplantation assay was used to show that matrix physical properties could significantly affect blood vessel formation by endothelial colony forming cells (ECFCs), providing initial evidence that matrix physical properties are important for clinical applications. Importantly, this new information provides insight into the control of collagen matrix properties and cell-ECM interactions, and can be directly applied to improve the design of collagen matrices for research and medical applications.