3D Printing of Tricalcium Phosphate/Poly Lactic-coglycolic Acid Scaffolds Loaded with Carfilzomib for Treating Critical-sized Rabbit Radial Bone Defects

Ye Li, Kegong Xie, Chong Wang, Chengliang Yang, Ke Huang, Feng Li, Chuanchuan Zheng, Jian Chen, Shujun Dong, Guangfeng Deng, Gege Huang, Qiaoyan Lu, Jia Liu, Kai Li, Yujin Tang, Liqiang Wang

Article ID: 405
Vol 7, Issue 4, 2021, Article identifier:

VIEWS - 106 (Abstract) 14 (PDF)

In Press, Corrected proof, Published online August 26, 2021


Abstract


The rapid development of scaffold-based bone tissue engineering strongly relies on the fabrication of advanced scaffolds and the use of newly discovered functional drugs. As the creation of new drugs and their clinical approval often cost a long time and billions of U.S. dollars, producing scaffolds loaded with repositioned conventional drugs whose biosafety has been verified clinically to treat critical-sized bone defect has gained increasing attention. Carfilzomib (CFZ), an approved clinical proteasome inhibitor with a much fewer side effects, is used to replace bortezomib to treat multiple myeloma. It is also reported that CFZ could enhance the activity of alkaline phosphatase and increase the expression of osteogenic transcription factors. With the above consideration, in this study, a porous CFZ/β-tricalcium phosphate/poly lactic-co-glycolic acid scaffold (designated as “cytidine triphosphate [CTP]”) was produced through cryogenic three-dimensional (3D) printing. The hierarchically porous CTP scaffolds were mechanically similar to human cancellous bone and can provide a sustained CFZ release. The implantation of CTP scaffolds into critical-sized rabbit radius bone defects improved the growth of new blood vessels and significantly promoted new bone formation. To the best of our knowledge, this is the first work that shows that CFZ-loaded scaffolds could treat nonunion of bone defect by promoting osteogenesis and angiogenesis while inhibiting osteoclastogenesis, through the activation of the Wnt/β-catenin signaling. Our results suggest that the loading of repositioned drugs with effective osteogenesis capability in advanced bone tissue engineering scaffold is a promising way to treat critical sized defects of a long bone.


Keywords


Bone defect, Cryogenic 3D printing, Bone regeneration, β-tricalcium phosphate, Carfilzomib

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References


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DOI: http://dx.doi.org/10.18063/ijb.v7i4.405

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