Biomaterial scaffolds are a fundamental component in tissue engineering, including for orthopedic applications such as fracture fixation and bone defect regeneration. To this end, it is advantageous for scaffolds to be bioactive and have sufficient mechanical strength. To inform the engineering of cell-seeded scaffolds, this chapter explores scaffold design, material selection, fabrication methods, and surface functionalization, as well as cell type, cell seeding, and culture conditions. Key considerations are the scaffold’s structural parameters (e.g., porosity) and material and biological properties, which can mimic the extracellular matrix, to optimize cell growth and tissue regeneration. This chapter also highlights the effects of cell type, seeding method, and culture environment on cell proliferation and osteogenesis, with a particular focus on advanced bioreactor systems for the culture of cell-seeded scaffolds.