In this study, we investigated the effect of intracapsular environment on the survival of anchorage-dependent cells (ADCs) encapsulated in alginate microcapsules with three different core structures, i.e. liquid, semi-liquid and microsphere-encapsulating semi-liquid core, using NIH 3T3 fibroblasts as an ADC model. For the latter, we fabricated poly (-caprolactone) microspheres and co-encapsulated them with the cells, to establish cell-substrate interactions in the capsule. The fibroblast cells co-encapsulated with the microspheres exhibited higher survival and growth than those without. This study provides a proof of concept for employing microspheres as a cell-friendly surface to establish intracapsular cell-substrate interactions thus prolonging the survival of encapsulated therapeutic ADCs.