Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate

S.-S. Cao; S.-Y. Li; Y.-M. Geng; K. Kapat; S.-B. Liu; F.H. Perera; Q. Li; H. Terheyden; G. Wu; Y.-J. Che; P. Miranda; M. Zhou

doi:10.1021/acsbiomaterials.1c00509

Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate

S.-S. Cao, S.-Y. Li, Y.-M. Geng, K. Kapat, S.-B. Liu, F.H. Perera, Q. Li, H. Terheyden, G. Wu, Y.-J. Che, P. Miranda, M. Zhou

Reconstructive Oral Care

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

© 2021 American Chemical Society.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.

Original language	English
Pages (from-to)	5727-5738
Journal	ACS Biomaterials Science and Engineering
Volume	7
Issue number	12
DOIs	https://doi.org/10.1021/acsbiomaterials.1c00509
Publication status	Published - 2021

Funding

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.

Funders	Funder number
Ministerio de Ciencia, Innovación y Universidades	RTI2018-095566–B-I00
National Natural Science Foundation of China	81671029
China Scholarship Council	201908440308
European Regional Development Fund
Bureau of Education of Guangzhou Municipality	1201610458
Guangzhou Science, Technology and Innovation Commission	201803040008, 201704030024
International Team for Implantology	881_2012
National Major Science and Technology Projects of China	2016YFC1102900
Junta de Extremadura	IB16094

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Cao, S.-S., Li, S.-Y., Geng, Y.-M., Kapat, K., Liu, S.-B., Perera, F. H., Li, Q., Terheyden, H., Wu, G., Che, Y.-J., Miranda, P., & Zhou, M. (2021). Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate. ACS Biomaterials Science and Engineering, 7(12), 5727-5738. https://doi.org/10.1021/acsbiomaterials.1c00509

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title = "Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate",

abstract = "{\textcopyright} 2021 American Chemical Society.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.",

author = "S.-S. Cao and S.-Y. Li and Y.-M. Geng and K. Kapat and S.-B. Liu and F.H. Perera and Q. Li and H. Terheyden and G. Wu and Y.-J. Che and P. Miranda and M. Zhou",

year = "2021",

doi = "10.1021/acsbiomaterials.1c00509",

language = "English",

volume = "7",

pages = "5727--5738",

journal = "ACS Biomaterials Science and Engineering",

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Cao, S-S, Li, S-Y, Geng, Y-M, Kapat, K, Liu, S-B, Perera, FH, Li, Q, Terheyden, H, Wu, G, Che, Y-J, Miranda, P & Zhou, M 2021, 'Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate', ACS Biomaterials Science and Engineering, vol. 7, no. 12, pp. 5727-5738. https://doi.org/10.1021/acsbiomaterials.1c00509

TY - JOUR

T1 - Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction

T2 - A Preclinical Translational Study in Primate

AU - Cao, S.-S.

AU - Li, S.-Y.

AU - Geng, Y.-M.

AU - Kapat, K.

AU - Liu, S.-B.

AU - Perera, F.H.

AU - Li, Q.

AU - Terheyden, H.

AU - Wu, G.

AU - Che, Y.-J.

AU - Miranda, P.

AU - Zhou, M.

PY - 2021

Y1 - 2021

N2 - © 2021 American Chemical Society.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.

AB - © 2021 American Chemical Society.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.

U2 - 10.1021/acsbiomaterials.1c00509

DO - 10.1021/acsbiomaterials.1c00509

M3 - Article

SN - 2373-9878

VL - 7

SP - 5727

EP - 5738

JO - ACS Biomaterials Science and Engineering

JF - ACS Biomaterials Science and Engineering

IS - 12

ER -

Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate

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