Induction of cell migration on synthetic polymer substrates through tailored cell-substrate matrix reciprocity

Limited epithelial cell migration on synthetic polymeric biomaterials, such as polyesters, presents a serious challenge to their use as scaffolds for artificial skin analogs. The mechanisms by which a physiologic matrix interface on such polymers may regulate and promote skin cell migration were the focus of this study. In vivo, the reepithelialization process, requiring the migration of epidermal keratinocyte cells across the wound bed, is central to wound healing. This migration process has been shown to be strongly influenced by a variety of extracellular matrix molecules, particularly collagen and fibronectin. Additionally, migration on synthetic polymers may also be influenced by intrinsic cellular remodeling events. The ability of synthetic biomaterials to activate cellular matrix remodeling and consequently promote keratinocyte migration, while currently untested, may present unique approaches to control and promote the kinetics of implant regeneration. In this study, the authors have quantified the migration behavior of epidermal keratinocytes on 50:50 poly D,L(lactide-glycolide) (PLGA) substrates, following exogenous and cell-derived substrate conditioning based on the model matrix proteins, collagen and fibronectin. The authors report that “non-conditioned” PLGA substrates elicited poor levels of keratinocyte migration, with a migration index of only 2.52±.28 after 48 h