3D-Printed Replica Bone Used to Identify Bone Cancer Treatment

Researchers from Nashville, Tenn., have used 3D printing to construct accurate replicas of human bone tissue to properly study, for the first time, how tumors and bones interact and how tumor-based bone disease might be treated. The new technique is a promising approach to stopping the formation of bone tumors.
 
The new approach was described by Dr. Julie Sterling of the Department of Veterans Affairs and Vanderbilt University in Nashville, Tenn., speaking on behalf of her colleagues from both institutions. Sterling recently addressed an audience at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS).
 
“Until now, it has not been possible to study the progress and treatment of bone cancers in the microenvironments of bones themselves or truly bone-like models,” Sterling said. “Instead, we have continued to grow cell cultures for study on tissue culture plates, essentially the modern answer to the Petri dish. So we used a combination of imaging and inkjet 3D printing technology to create 3D tissue-engineered constructs (TECs) that reproduce the form and mechanics of trabecular bone—the tissue found at the ends of long bones—as well as in the vertebrae of the spinal column and other places.”
 
The team made 3D-printed TECs of the tissue in three different human bone areas— the head of the femur, the tibial plateau and lumbar vertebrae—and tested them to ensure they accurately mirrored the originals. These were used for a variety of studies that involved growing cell cultures, including stem cell cultures and bone-based breast cancer cell cultures.
 
“Importantly, we studied the behavior of drug treatments on tumors cultured on bone-like 3D TECs and found a remarkable difference in effect when compared with tumors cultured on the conventional tissue culture plates,” Sterling said. “When bone-based breast cancer cells (bone-metastatic MDA-MB-231) cultured on the 3D TECs were treated with the inhibitor drugs Cilengitide or SD208 (intended to inhibit the growth and invasiveness of tumour cells), the apparent benefits that had been found in the tissue culture plates environment were not there.”
 
“But when the treatment was the Gli2 inhibitor GANT58 (which inhibits signaling en route to the cell receptors), the treatment had a similar and significant effect whether in the 3D TEC environment or the tissue culture plate environment,” she added. “This suggests that an effective way of blocking the establishment of tumors in bone may be to target factors downstream of cell receptors rather than targeting the cells directly. It also shows how important it can be to have a physical bone-like environment for the study of tumors and treatments.”
 
The study, titled “3D Tissue Engineered Constructs for Modeling Tumor-Induced Bone Disease,” was completed on an earlier version of 3D Tissue Engineered Constructs (TECs) that has now been superseded.
 
The 3D TECs were designed using imaging in tandem with inkjet 3D printing technology to recapitulate the mechanical and morphometric properties of trabecular bone. The 3D-printed TECs exhibited no significant differences in bone morphometric parameters compared to the human femoral head, tibial plateau, and lumbar spine templates from which they were prepared (p < 0.05). The substrate modulus of the TECs was 266 MPa, which is within the reported range for trabecular bone (93 – 266 MPa).