Prefabricated 3D-printed tissue-engineered bone for mandibular reconstruction: A preclinical translational study in primate

The advent of three dimensionally (3D) printed customized bone grafts using different biomaterials has enabled repairs of complex bone defects in various in vivo models. However, studies related to their clinical translations are truly limited. Herein, 3D printed poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PLGA/TCP) and TCP scaffolds with or without recombinant bone morphogenetic protein −2 (rhBMP-2) coating were utilized to repair primate’s large-volume mandibular defects and compared efficacy of prefabricated tissue-engineered bone (PTEB) over direct implantation (without prefabrication). 18F-FDG PET/CT was explored for real-time monitoring of bone regeneration and vascularization. After 3-month’s prefabrication, the original 3D-architecture of the PLGA/TCP-BMP scaffold was found to be completely lost, while it was properly maintained in TCP-BMP scaffolds. Besides, there was a remarkable decrease in the PLGA/TCP-BMP scaffold density and increase in TCP-BMP scaffolds density during ectopic (within latissimus dorsi muscle) and orthotopic (within mandibular defect) implantation, indicating regular bone formation with TCP-BMP scaffolds. Notably, PTEB based on TCP-BMP scaffold was successfully fabricated with pronounced effects on bone regeneration and vascularization based on radiographic, 18F-FDG PET/CT, and histological evaluation, suggesting a promising approach toward clinical translation.This work was supported by the National Natural Science Foundation of China [Grant No. 81671029], the National Major Science and Technology Project of China [Grant No. 2016YFC1102900], the Guangzhou Science, Technology and Innovation Commission [Grant Nos. 201803040008 and 201704030024], the International Team for Implantology [Grant No. 881_2012], the Bureau of Education of Guangzhou Municipality [Grant No. 1201610458], China Scholarship Council (No. 201908440308), Spanish Ministry of Science, Innovation and Universities [Grant No. RTI2018-095566–B-I00], and Junta de Extremadura [Grant No. IB16094]; the last two cofinanced with European Regional Development Funds.peerReviewe