ABSTRACT
The design of biomimetic materials can benefit from the systematic incorporation and presentation of specific ligand molecules that can selectively regulate cell functions, including cell proliferation, differentiation, adhesion, and migration (1, 2). Various properties of ligands can affect cell signal transduction processes through interactions with surface receptors, e.g., ligand surface concentration, strength of ligand-receptor adhesion, degree of receptor occupancy by the ligand, and ligand affinity (3). Recently, the ligand microdistribution on biomaterial surfaces has also been shown to modulate the valency of receptor-ligand binding, with effects on cell spreading (4). The presence of three-dimensional microtopography can further alter ligand-elicited cell functional processes such as cell adhesive and motility responsiveness (5). Thus, the design of threedimensionally clustered ligand interfaces may be warranted to mimic the regulatory control of cell function via native ligand presentation within the extracellular matrix (ECM) of a tissue. Ligand microinterfaces that exhibit more complex and dynamic cell interactions can also be envisioned, such as those that elicit receptor-mediated cell binding and adhesion but also activate cell signaling through active substrate internalization, through a process called phagocytosis (6). Such interfaces occur frequently in vivo, when cells contact a ligand-presenting surface and migrate on it through ligand internalization, a process called phagokinetic migration (7). For example, during wound healing, skin epidermal cells called keratinocytes have been shown to phagocytose ECM ligand debris that lies directly in their migratory path. Thus, the design of phagokinesis-promoting ligand interfaces may be of value to the development of tissue scaffold configurations that promote the kinetics of scaffold coverage or cell infiltration (8, 9). This chapter presents key results of our study on the modulation of skin epidermal cell migratory behavior through the use of ligand-as so dated microdepots (LAMs) on synthetic polymers. The results focus on the short-term dynamic control of LAM regulation, as well as the longer term molecular control of the cell migratory response.
