The aim of this study was to compare the cell compatibility of silk and polyglycolic acid (PGA) scaffolds cultured in vitro with mesenchymal stem cells (MSCs) and peripheral blood mononuclear cells (PBMCs) to their biocompatibility in vivo following implantation. Scaffolds were knitted with silk or PGA thread and the average efficiency of cell attachment was 35 +/- 4% and 17 +/- 2% in the PGA and silk scaffold groups. Thus, the initial attachment of the MSC cells to the PGA scaffold was superior to the initial attachment of the cells on the silk scaffold. After 21 days in culture, the average cell density on the silk scaffold was 5.8 +/- 0.5 x 10(5) cells, and the average cell density of the PGA scaffolds was 6.34 +/- 0.5 x 10(5) cells. In addition, there was no cell cytoxicity observed with either scaffold. However, the immune response of in vitro cultured PBMCs was significantly higher with the PGA scaffold than with the silk scaffold. The proliferation of the PBMCs cultured on the PGA scaffold was two times greater than that of those cultured on the silk scaffold after 3 days of culture. In addition, the secretion of IL-1 by the PBMCs cultured on the PGA scaffold was superior to that of the PBMCs cultured on the silk scaffold. The secretion of IL-1beta and IFN-gamma was increased by about 50% when the PBMCs were cultured with the PGA scaffold. Silk and PGA scaffolds were also implanted subcutaneous in rats. Histological evaluation of the scaffold explants revealed the presence of monocytes and macrophages in PGA scaffold. The inflammatory tissue reaction was more conspicuous on the PGA scaffold than on the silk scaffold. These results suggest that the results of in vitro PBMC cultures were more closely related to the in vivo results of implantation than the results of in vitro MSC cultures.