Cell Guidance in Tissue Engineering: SDF-1 Mediates Site-Directed Homing of Mesenchymal Stem Cells within Three-Dimensional Polycaprolactone Scaffolds

Abstract

Cell guidance is a new tissue engineering concept aimed at total in vivo tissue engineering without the need for cell seeding. This technique aims to create a biomimetic environment through constant delivery of cytokines to different areas of an implanted scaffold, such that site-specific homing of cells can be achieved. In this study, expression of CXCR4 on mesenchymal stem cells (MSCs) was characterized by immunohistochemistry and flow cytometry, subsequent to which chemotaxis toward stromal cell-derived factor 1 (SDF-1) was demonstrated. In a subsequent three-dimensional in vitro study, MSCs were shown to migrate within a polycaprolactone scaffold in response to SDF-1, such that polarized tissue formation could be achieved. A customized cytokine microdelivery system comprising a reservoir housing system and microneedle apparatus was fabricated to ensure constant delivery of SDF-1 to the scaffold. Following on this experiment, we demonstrated in an in vivo rat bone tissue engineering model that a cytokine combination consisting of vascular endothelial growth factor, SDF-1, and bone morphogenetic protein-6 delivered at 10-day intervals through the microneedle apparatus could lead to tissue formation through migrating cell fronts, with evidence of angiogenesis and vascularization without the need for cell seeding on scaffolds prior to implantation. In summary, cell guidance offers an advancement in cellular methodology for tissue engineering, and promises a novel, minimally invasive option for tissue regeneration.