A hybrid scaffold was obtained by the deposition of a thin network of submicron fibrin fibrils on the microporous walls of a macroporous poly(L-lactide) (PLLA) three-dimensional structure. The fibrin coating is homogeneous across the entire substrate and allowed the pore structure remain open in the hybrid scaffold. The elastic modulus of the hybrid scaffold (0.65 MPa) was increased up to twofold compared to the pure PLLA scaffold (0.29 MPa). Mouse pre-osteoblastic cells, MC3T3, were seeded on both pure PLLA and hybrid scaffolds, and cultured for 3, 6, and 24 h. The coating enhanced the cell colonization and proliferation and provided a more homogeneous distribution of cells within the scaffolds. In addition, the coating improved the scaffold adhesion properties by supplying new binding sites to the cells that modify the transmembrane receptors involved in initial cell adhesion mechanism. The expression of the β3 integrin was observed in cells cultured on fibrin-coated scaffolds instead of the α5 integrin, which was expressed in the uncoated scaffold. These hybrid PLLA/fibrin scaffolds have cell culture features suitable to promote early tissue regeneration.