3D printed replica bone used to identify bone cancer treatment
• Researchers in Nashville, Tennessee, pioneer the use of 3D printing to create replica bone tissue
• Replica bone tissue used for microenvironment study of bone cancers and treatments
• Study results show remarkable difference from earlier findings about approaches to treatment
May 18, 2016, Rome, Italy. Press Dispensary.
A team from Nashville, Tennessee, has used 3D printing to construct accurate replicas of human bone tissue in order to study properly, for the first time, how tumours and bones interact and how tumour-based bone disease might be treated. And already the new technique is suggesting what may be the best approach to stopping tumours being established in bone.
The new approach was described in Rome today by Dr Julie Sterling of the Department of Veterans Affairs and Vanderbilt University in Nashville, Tennessee, speaking on behalf of her colleagues from both institutions. Dr Sterling was addressing an audience at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS).
Dr Sterling said: "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. 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 bone 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 - tested to show that 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.
Dr Sterling continued: "Importantly, we studied the behaviour of drug treatments on tumours cultured on bone-like 3D TECs and found a remarkable difference in effect when compared with tumours cultured on the conventional tissue culture plates.
"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 signalling 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.
"This suggests that an effective way of blocking the establishment of tumours 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 tumours and treatments."
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Notes for editors
About the study
The study, titled "3D Tissue Engineered Constructs for Modeling Tumor-Induced Bone Disease" was carried out in Nashville, Tennessee, by researchers from the Department of Veterans Affairs and Vanderbilt University. The study 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).
Culture of rat MSCs on the bone-like TECs exhibited a significant (p < 0.05) 1.7-fold increase in mineralization compared to collagen-like TECs. Culture of bone-metastatic MDA-MB-231 breast cancer cells on bone-like TECs in a perfusion bioreactor showed a significant (p < 0.05) >5-fold increase in expression of integrin beta 3, Gli2, and PTHrP compared to collagen-like TECs.
Importantly, drug response differed remarkably when tumors were cultured on bone-like 3D TECs compared to tissue culture well plates. When MDA-MB-231 cells were treated with the integrin inhibitor Cilengitide or the TGF-beta receptor kinase inhibitor SD208 in 2D culture, expression of Gli2 and PTHrP significantly decreased 2 - 3-fold (p < 0.01). However, treatment with these drugs did not significantly reduce Gli2 or PTHrP expression on 3D bone-like TECs. In contrast, treatment with the Gli2 inhibitor GANT58 significantly reduced both Gli2 and PTHrP expression >3-fold (p < 0.01) in both 3D and 2D.
About ECTS 2016
ECTS 2016 is the 43rd annual congress of the European Calcified Tissue Society (ECTS), held in Rome, Italy on May 14-17, 2016, in collaboration with the Cancer and Bone Society.
ECTS 2016 gives delegates the opportunity to collaborate with leading international researchers and clinical colleagues. Main discussion points are the latest in high quality science and research to benefit clinical practice.
ECTS 2017, the 44th congress, will be held in Salzberg, Austria, May 13-16, 2017.
See http://ects2017.org .
About The European Calcified Tissue Society
The European Calcified Tissue Society (ECTS) is the major organisation in Europe for researchers and clinicians working in the field of calcified tissues and related fields. ECTS acts as a forum for the dissemination of high quality research through its annual meeting, the European Symposium on Calcified Tissues, and through training courses and workshops.
Calcified tissues are central to a healthy skeleton and to bone disorders - such as osteoporosis, back pain and fractures - that make life a misery for countless people. Children can inherit some forms of bone diseases causing bone pain, shortness and deformed limbs.
For further information, please contact:
Roberta Mugnai, ECTS executive director
European Calcified Tissue Society (ECTS)
Tel: + 32 476 520 716
ECTS 2016: http://2016.ectscongress.org/
Event hashtag: https://twitter.com/hashtag/ECTS2016