Human retinal progenitor cells (hRPCs), isolated from fetal retina, require extracellular matrix proteins such as fibronectin or laminin for successful attachment and self-renewal in vitro. Here we have shown that a novel synthetic vitronectin-mimicking surface supports self-renewal and multipotency of hRPCs in a chemically defined culture system. The morphology, adhesion, and proliferation of hRPC were equivalent on a novel vitronectin-mimicking surface (Synthemax) compared to a fibronectin-coated surface. When evaluated using real-time polymerase chain reaction, Western blotting, and flow cytometry, both surfaces maintained self-renewal of hRPCs, as shown by similar expression levels of Sox2, Nestin, cMyc, Klf4, and Pax6, with no change in integrin beta1 and integrin alpha5 expression. We suggest that the use of synthetic, xeno-free surfaces such as Synthemax will be useful for basic research studies, as well as development of translational strategies aimed at using stem cell transplantation to treat disease.