A significant challenge facing the fabrication of effective bone implants is the manipulation of synthetic materials to construct structures that mimic the complex form of native bone. As a technique attracting considerable attention for multiple applications, three-dimensional (3D) printing is being explored to generate synthetic biocompatible materials for guided bone regeneration and bone substitutes. However, the two principal existing techniques require an annealing step that can lead to mineral decomposition and the introduction of impurities. Now, a research group at the Russian Academy of Sciences has developed a method involving 3D printing of octacalcium phosphate (OCP) that does not require a heating step. The printed OCP block was implanted into a bone defect of size (20 mm) larger than mouse cranial bone defects that can be restored by native osteogenesis. The defect size was reduced 2.5 times in diameter over 6.5 months. The research is reported in the June 8 issue of Frontiers in Bioengineering and Biotechnology (DOI: 10.3389/fbioe.2015.00081).
“Vladimir S. Komlev et al.’s work is really exciting, innovative, and timely. The current paper is going to give a new direction to the current biomaterials processing research,” says Chandra Sekhar Tiwary, a researcher from Rice University and the Indian Institute of Science. “The use of simple and easily scalable 3D printing technology for shaping ceramic biomaterials into a complicated shape will definitely attract many biomaterials researchers. Printing ceramic using 3D printing with the current method is not just useful for biomaterials, but also for ceramic processing industries. Also, shaping the structure from a bottom-up approach opens a new direction of engineering materials,” Tiwary says.
Previous studies revealed that OCP ceramics facilitate bone marrow cell differentiation and spur osteogenesis after in vivo implantation. Komlev and colleagues thus brought ideas from this technology to the 3D printing of ceramics. The OCP implant was formed by a two-step process. The desired 3D ceramic model was first uploaded to a custom-designed 3D printer; dicalcium phosphate dihydrate (DCPD) was then formed during the printing process thanks to the interaction between tricalcium phosphate powder and diluted phosphoric acid, which serves as a binder liquid and ink. Subsequent chemical treatment of the printed DCPD materials transformed them into a needle-like OCP phase. The resultant OCP materials exhibited a threefold increase in compressive strength compared to 3D-printed DCPD samples due to the formation of OCP crystals and enhanced bonding between particles.
General views of printed implant before (left top) and after implantation (right top). Scanning electron micrograph (left bottom) shows a flower-like morphology of dicalcium phosphate dihydrate crystals. Histotopogram (at 100× magnification) (right bottom) indicates the margin of the regenerated bone tissue that retains the implant. Credit: Vladimir S. Komlev.
Evaluation of the new materials in vivo as bone graft materials demonstrated that fibrous tissues filled whole defect areas, including the pores of the printed implant. The printed materials supported bone growth at the defect edges—which are peripheral sites containing bone cell producing osteoinductive factors—and developed thickness of the growing fibrous tissue. The 2.5 times reduction in diameter in a defect region where very little spontaneous bone repair took place demonstrates success in bone tissue regeneration. However, the center of the defect showed no sign of osteogenesis. Komlev believes that for such a large bone defect, the OCP 3D-printed graft should also comprise osteoinductive components such as cells, growth factors, and gene constructions to increase the activity of bone tissue formation.
“The development of this approach opens new possibilities for creating modern bioengineered equivalents of hard tissues of humans,” said Komlev. “Nevertheless, we consider the results obtained so far in bone repair by the 3D printing approach to be very encouraging, but not optimal. To overcome the difficulties related to scientific, clinical, and commercial areas, innovative developments are further proposed. In particular, new types of 3D advanced ceramic scaffolds based on OCP and plasmid DNA with the gene encoding vascular endothelial growth factor have been developed by us. We hope that these novel methodologies will truly represent a new product—and possibly a new gold standard—in the tissue engineering field of bone repair.”
