The present invention concerns biologically-active cell-free scaffolds composed of extracts of cellular and/or extracellular compartments for use in tissue regeneration. The present invention also contemplates the novel concept of redesigning the biological scaffold by seeding cells thereon followed by cell elimination. Cells are seeded on the scaffold for a period of time during which a dynamic interaction occurs between the scaffold and the seeded cells, resulting in reshaping of the scaffold architecture and integration of newly synthesized matrix elements. Redesigning may improve the physical and biological characteristics of the scaffold, and also improve the matching of the scaffold to treat a specific target tissue or a specific patient, by seeding tissue-specific cells or by seeding cells which are autologous to a patient, respectively.