The successful materials design for bone-tissue engineering needs to understand the structure and composition of host bone tissue, and selecting appropriate biomimetic natural or tunable synthetic materials (biomaterials), such as polymers, bioceramics, metals, and composites. Materials that improve bone tissue engineering have tremendous potential for clinical applications to treat and regenerate various bone injuries and fractures. The drive to design bone grafts for bridging the gaps in orthopedic tissue regeneration results in a significant research thrust for designing and developing material for bone tissue regeneration. Recently, numerous challenges, including biomaterial designing, can well suit the biological, chemical and mechanical microenvironment of natural orthopedic tissues and adopt vascularization. Novel bio-inspired materials attempt to enhance the biofunctionality that reconstruct microlevel biofactor and topographical signals from the extracellular environment are rapidly developing. The most important paradigm shift in orthopedic tissue engineering is the careful selection of scaffold, signals, and cell types to design biomaterials. Notwithstanding, the clinical outcome of orthopedic tissue regeneration was so vibrant years ago; however, so far, it failed to achieve the expected results and failed to translate in the clinical setting. In the current review, we discuss the aims and mechanism of bone tissue regeneration, biomaterial designing, and orthopedic tissue engineering requirements. Next, we highlight the principle for orthopedic tissue engineering and describe the strategies for enhancing material Bio-functionality. Finally, we give the bench to bedside concept and concluding remarks with a special focus on future. The main purpose of current paper is to give a comprehensive overview, which is helpful for the researcher to distill this information and design future research strategies for designing materials for orthopedic and bone tissue engineering.