Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) with the potential to differentiate in a limited number of other tissue types. Some evidence has suggested the modulation of DPSC growth may be mediated, in part, by exogenous extracellular matrix (ECM) glycoproteins, including fibronectin (FN) and laminin-5 (LN5). Although preliminary research suggests that some ECM glycoproteins may work as functional biomaterials to modulate DPSC growth responses, the primary goal of this project is to determine the specific effects of FN and LN5 on DPSC growth and viability. Using an existing DPSC repository, n = 16 DPSC isolates were cultured and 96-well growth assays were performed, which revealed FN, LN5 and the combination of these were sufficient to induce statistically significant changes in growth among five (n = 5) DPSC isolates. In addition, the administration of FN (either alone or in combination) was sufficient to induce the expression of alkaline phosphatase (ALP) and dentin sialophosphoprotein (DSPP), while LN5 induced the expression of ALP only, suggesting differential responsiveness among DPSCs. Moreover, these responses appeared to correlate with the expression of MSC biomarkers NANOG, Oct4 and Sox2. These results add to the growing body of evidence suggesting that functional biomaterials, such as ECM glycoproteins FN and LN5, are sufficient to induce phenotypic and differentiation-specific effects in a specific subset of DPSC isolates. More research will be needed to determine which biomarkers or additional factors are necessary and sufficient to induce the differentiation and development of DPSCs ex vivo and in vitro for biomedical applications.