Indirect 3D printing in tissue engineering: expanding materials used for improved scaffold functionality

During the past decades, three-dimensional (3D) printing processes have come as the foremost technology for the fabrication of scaffolds in tissue engineering (TE). The advanced technical approaches followed by 3D printing have provided architectural versatility and customizability. Despite the many progresses, several limitations have emerged related to the available, processable range of materials offering desired functions equivalent or suitable for the target tissue. To address the issue raised, several novel methodologies have been developed where a 3D printed sacrificial mold serves to produce the final scaffold from a wide range of materials, even from the difficult-to-print or unprintable materials. These techniques are known as "indirect 3D printing" (I3DP), which like the direct 3D printing approaches, are able to manufacture controlled, patient-specific constructs. Direct 3D printing faces limitations like poor printability of natural soft polymers and bio-ceramics, restricted resolution of the printed objects, and a limited range of compatible materials. Indirect 3D printing overcomes these by enabling the use of a much wider variety of materials and creating high-strength ceramic scaffolds without clogging or structural defects. This method also provides superior resolution with less parameter optimization and minimizes material waste, making it more efficient. The current review paper presents a state-of-the-art study of how indirect 3D printing is being utilized in tissue engineering. The focus is given to the details of steps required for the production of scaffolds including mold design, software, 3D printing machines used, mold and scaffold materials, mold removal approaches, combination with other pore forming methodologies and the area of applications in tissue engineering.