Although tissue-engineered scaffolds made from collagen sponge are suitable for cell infiltrating, easily supplying oxygen and nutrients to cells, and removing the waste products, their mechanical properties are not satisfactory to be used as scaffold materials for tissue engineering applications. To improve mechanical properties of collagen, a novel porous scaffold for bone tissue engineering was prepared with collagen sponge reinforced by polypropylene/polyethylene terephthalate (PP/PET) fibers. Collagen solution (6.33 mg/mL) with PP/PET fibers (collagen/fiber ratio [w/w]: 1.27, 0.63, 0.42, 0.25) was freeze-dried, followed by cross-linking of combined dehydrothermal and glutaraldehyde. A scanning electron microscopy-based analysis of surface of the sponges demonstrated that the sponge with collagen/fiber <0.25 exhibited homogenous and interconnected pore structure with an average pore size of 200 μm. Incorporation of PP/PET fibers significantly enhanced the compressive strength of the collagen sponge. Proliferation and osteogenic differentiation of mesenchymal stem cell in collagen sponges reinforced with PP/PET fibers incorporation were significantly enhanced compared with collagen sponge without PP/PET incorporation. We conclude that incorporation of PP/PET fibers not only improves the mechanical properties of collagen sponge, but also enables mesenchymal stem cells to positively improve their proliferation and differentiation.