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RESEARCH ARTICLE

3D Printing of Tricalcium Phosphate/Poly Lactic-co-

glycolic 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 ,
1†
1†
1
1
1
2†
1
Jian Chen , Shujun Dong , Guangfeng Deng , Gege Huang , Qiaoyan Lu , Jia Liu *, Kai Li *,
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3
1
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5
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Yujin Tang *, Liqiang Wang 6
1
1 Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, PR China
2 School of Mechanical Engineering, Dongguan University of Technology, Songshan Lake, Dongguan, Guangdong, PR China
3 Department of Rehabilitation medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise,
Guangxi, PR China
4 Youjiang Medical University for Nationalities, Baise, Guangxi, PR China
5 The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, PR China
6 State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong
University, Shanghai, 200240, China
† These authors contributed equally to this work
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

*Correspondence to: Jia Liu, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi,
533000, China: liujia0111@live.cn; Kai Li, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province,
510000, China: lk516433415@smu.edu.cn; Yujin Tang, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for
Nationalities, Baise, Guangxi, 533000, China: tangyujin1967@163.com
Received: July 12, 2021; Accepted: August 2, 2021; Published Online: September 14, 2021

Citation: Li Y, Xie K, Wang C, et al., 2021, 3D Printing of Tricalcium Phosphate/Poly Lactic-co-glycolic Acid Scaffolds Loaded
with Carfilzomib for Treating Critical-sized Rabbit Radial Bone Defects. Int J Bioprint, 7(4):405. http://doi.org/10.18063/ijb.
v7i4.405

© 2021 Li, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is cited.
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