(770f) Novel pH-Responsive Scaffolds with Self-Actuating Oxygen Transport

The lack of vascularization in implanted tissue engineered constructs has been one of the principal challenges of tissue engineering. Cells residing at a critical distance (>100 microns) from the blood supply on an implanted scaffold are limited by diffusion, nutrient delivery and waste removal. In this study, we present scaffolds composed of a pH-sensitive polymer, dimethylaminoethyl methacrylate (DMAEMA) and biocompatible polymer, 2-hydroxyethyl methacrylate (HEMA).  Our pH-sensitive scaffolds increase their pore size when exposed to low pH, thereby allowing an increase in flux. In vitro pO₂ measurements and cell viability studies confirm higher oxygen levels and cell proliferation in DMAEMA/HEMA scaffolds compared to nonresponsive HEMA scaffolds. We conducted in vivo studies which corroborated increased cell viability in pH-responsive scaffolds. Immunofluorescence staining of human umbilical vein endothelial cells (HUVECs) seeded in scaffolds after implantation in mice showed that the pH-sensitive DMAEMA/HEMA (30/70, mol/mol) scaffolds provided an environment more favorable to cell survival, as a significant number of cells were present after implantation compared to HEMA scaffolds.  Additionally, DMAEMA/HEMA (30/70, mol/mol) scaffolds exhibited vessel formation while cells seeded onto HEMA scaffolds did not. We present a scaffold design that significantly increases cell survival by increasing oxygen availability through a self-actuating, pH-responsive mechanism.