Hope is that tissue engineering will provide a solution to meet the growing needs for bone substitutes. Among the potential solutions, three-dimensional (3D) printing is a promising method to fabricate functional bone substitutes especially for treatment of complex and critical-sized bone defects. Despite its encouraging achievements, 3D printing of bone substitutes still faces serious challenges including mechanical strength, shape complexity, optimization of pore parameters, and vascularization. The newer approach, that is, 3D bioprinting, is also confronted with challenges, which have prevented the realization of the dream of fabricating functional patient-specific bone substitutes. This article reviews the major challenges toward 3D printing and bioprinting of bone substitutes and recent studies addressing them. Potential solutions for each challenge and future directions are also provided. Impact Statement This review provides a current overview of the challenges in 3D (bio)printing of bone substitutes and summarizes the potential solutions.
Keywords: 3D printing; biomaterials; bioprinting; bone substitutes; tissue engineering.