Three-dimensional biodegradable porous scaffolds play an important role in tissue engineering as temporary templates for transplanted cells to guide the formation of the new organs. Two kinds of novel biodegradable porous scaffolds for tissue engineering have been developed by our group by hybridizing synthetic poly(α-hydroxy acids) with naturally derived collagen. One is their hybrid sponge prepared by introducing collagen microsponges in the pores of poly(α-hydroxy acids) sponge. The other one is their hybrid mesh prepared by forming collagen microsponges in the interstices of poly(α-hydroxy acids) mesh. The hybrid scaffolds were used for three-dimensional culture of fibroblast, tenocytes, chondrocytes and mesenchymal stem cells for tissue engineering of skin, ligament, cartilage and osteochondral tissue. These cells adhered and spread well in the hybrid scaffolds, proliferated, secreted extracellular matrices and formed the respective tissues. The synthetic polymer sponge, or mesh serving as a skeleton, reinforced the hybrid scaffolds and resulted in easy handling, while the collagen microsponges provided the hybrid sacffolds with a microporous structure and hydrophilicity, and therefore, easy cell seeding. The hybrid scaffolds will be useful for tissue engineering.