In ‘3D Printing of Bioceramic Scaffolds—Barriers to the Clinical Translation: From Promise to Reality and Future Perspectives,’ authors Kang Lin, Rakib Sheikh, Sara Romanazzo, and Iman Roohani explore 3D printing bioceramics and ‘hurdles’ for the clinical setting, along with current limitations and required parameters.

Bone regeneration is a very common motivator behind the fabrication of scaffolds, as researchers seek more suitable mechanical properties in materials and stability in structure. This continues to be a source of challenge in labs around the world, as well as hospitals, as medical professionals strive to improve treatment for patients with bone defects stemming from issues like:

• Trauma
• Infection
• Tumor resection
• Skeletal abnormalities
• Compromised regenerative process

The authors point out that autografts are the ‘gold standard’ for bone regeneration efforts, stimulating bone cells to grow, but also requiring a second surgery for the harvesting of the graft materials—presenting risk of infection and pain. These procedures may not be easily performed either in older patients or individuals with malignancies, or those who have had substantial bone loss already. Allografts are popular too, but also pose challenge due to lack of affordability, shortage of donor tissue, risk of further disease, and more.

The emerging field of bioprinting and the use of 3D printed, biocompatible scaffolds offers many benefits over other techniques, as these structures can not only regenerate tissue but continue to support cell activity and growth. 3D printing of scaffolds offers great potential as they can be produced on-demand in a patient-specific format.

“In recent years, the application of additive manufacturing in bone tissue engineering has been growing exponentially,” stated the researchers.

“Physical attributes of scaffolds such as pore size, pore shape, interconnectivity between pores and porosity, and overall shape of the scaffold can be designed as a 3D model and fabricated by the printing machine.”

Additive manufacturing has developed into a technology that has made significant impacts in the medical realm; however, challenges continue within 3D printed bioceramics.

“Some of these challenges are attributed to the nature of bioceramics, i.e., inherent brittleness, the necessity of high temperature for sintering, and the rest are related to the limitation of printing technique, preoperative planning, and postoperative complications, in which we will elaborate more in the following,” the researchers wrote.

Schematic of common additive manufacturing techniques including 3D printing (3DP), direct-ink writing (DIW), stereolithography (SL), and selective laser sintering (SLS) for printing bioceramic scaffolds and their advantages and disadvantages.

Optimization of parameters is key in 3D printing for bioceramics, along with suitable post-processing techniques. Brittleness is a constant issue too, as ceramics are inherently brittle and pose serious handling concerns.

“In many natural materials such as nacre or bone, high toughness is achieved through a hierarchical arrangement of organic (tough phase) and inorganic (stiff phase) components at different length scales from nano to micro and macro, but such structures are extremely difficult to mimic and fabricate,” explained the researchers. “Nevertheless, these solutions seem to be impractical to be implemented in the 3D printing of bioceramics. Firstly, bioceramics scaffolds are required to be sintered at high temperatures; therefore, they cannot be integrated with biopolymers while printing, and secondly, the current resolution of printing techniques is limited to several microns that do not allow nanoscale control in fabrication.”

As challenges continue with prefabricated scaffolds, the researchers suggest in situ printing directly into the wound, using a small, handheld device, ‘allowing the surgeon to directly construct a desirable 3D scaffold into the defect. This new process has not only been shown to be successful but also offers benefits over the use of prefabricated scaffolds in affordability and reduction of pre-operative planning time.

Materials can be an issue, however, as the process requires a new ink: “one that does not require high temperatures for densification, allows hardening in physiological condition without generating heat or toxic by-products and proper viscoelastic property.”

The researchers suggest the use of bioceramic inks, created in a non-toxic fashion.

“Besides technical issues, there are other obstacles ahead of translation of printed scaffolds such as stringent regulatory requirements and lack of evidence for biological performance in clinical surgery,” stated the researchers.

“Despite all the advances in additive manufacturing techniques for bioceramics, there are still major gaps in this field relative to dimensional accuracy, time-consuming optimizations, invasive postprocessing steps such as sintering that prevent integration of scaffold with living cells and growth factors or biopolymers during printing, and nanoscale control during fabrication.”

The creation of a variety of different scaffolds for bioprinting is a continuing focus in the 3D printing realm, especially as scientists reach to find better ways to sustain cells in tissue engineering—from refining structural design to reconstructing the human jaw to actually implanting esophageal cells without using scaffolds.

Schematic of the main challenges in additive manufacturing of bioceramic scaffolds, proposed solution strategies, and future outlook where the new research might overcome those challenges.[Source / Images: ‘3D Printing of Bioceramic Scaffolds—Barriers to the Clinical Translation: From Promise to Reality and Future Perspectives’]