Tissue-engineered scaffolds have played a decisive role in the repair and regeneration of a diverse range of tissues, including bone. These scaffolds not only provide a supporting matrix for cells especially in bone tissue engineering, but also provide essential environments for cells to spread, migrate, multiply, and conform to differentiation into specific lineage. For this, bone scaffolds should be tuned physico-chemically, to successfully repair and regenerate bone. Unlike conventional scaffolds that temporarily fill defects and need secondary surgery for their replacement and/or removal, promisingly therapeutic scaffolds have utilized a variety of biological actions that favor and trigger cells, especially stem cells, to carry out relevant therapeutic roles . Bone repair or regeneration is a part of a complex dynamic event that involves many molecules and cells. After scaffold implantation, the therapeutic actions should thus be harmonized with the biological events and even facilitate a better healing process. Key events in the active healing process include mild inflammatory reactions with no tissue rejection, substantial angiogenesis to form blood vessels, recruitment of progenitor/stem cells, and driving these cells toward osteogenic lineage and finalizing matrix maturation. Therefore, tailoring the scaffolds to aid and stimulate these biological processes is an important milestone for scaffold-based bone engineering. In this topical review, we highlight designs of therapeutically relevant scaffolds that trigger cellular functions that benefit the repair and regeneration of bone, which will lead to the development of ideal scaffolds for bone engineering.