AbstractThe aim of this study was to develop a nanosized, controlled growth factor release system to incorporate into tissue engineering scaffolds and thus activate the cells seeded in the scaffold. Nanocapsules of poly(lactic acid‐co‐glycolic acid) (PLGA) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) were loaded with the bone morphogenetic proteins BMP‐2 and BMP‐7, respectively, and with bovine serum albumin (BSA), the model protein. BSA‐loading efficiency and release kinetics were used to determine the most appropriate nanocapsule pair to achieve the delivery of growth factors in a sequential manner, as occurs in natural processes. BSA‐encapsulation efficiency was highest when the polymer concentration used in the preparation of PLGA and PHBV nanocapsules was 10% (w/v) (84.75% and 16.72%, respectively). Release of BSA was faster from PLGA than it was from PHBV. Based on the encapsulation efficiency and release data, 10% PLGA and 10% PHBV nanocapsules were chosen to provide the early BMP‐2 and later BMP‐7 release, respectively. Simultaneous, sequential delivery and individual release of the BMPs were studied for 7, 14, and 21 days, using rat bone marrow mesenchymal stem cells. Individual BMP‐2 release suppressed cell proliferation while providing higher alkaline phosphatase activity with respect to BMP‐7. The sequential delivery of BMP‐2 and BMP‐7 provided slightly lower proliferation than did simultaneous delivery, but the highest alkaline phosphatase activity of all indicated a synergistic effect on the osteogenic differentiation of mesenchymal stem cells caused by the use of the two growth factors in a sequential fashion. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010