A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration

Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metall...

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Main Authors: Rayan Fairag, Li Li, Jose Luis Ramirez-GarciaLuna, M. Scott Taylor, Brian Gaerke, Michael H. Weber, Derek H. Rosenzweig, Lisbet Haglund
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.654518/full
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author Rayan Fairag
Rayan Fairag
Rayan Fairag
Li Li
Li Li
Jose Luis Ramirez-GarciaLuna
M. Scott Taylor
Brian Gaerke
Michael H. Weber
Michael H. Weber
Derek H. Rosenzweig
Derek H. Rosenzweig
Lisbet Haglund
Lisbet Haglund
Lisbet Haglund
author_facet Rayan Fairag
Rayan Fairag
Rayan Fairag
Li Li
Li Li
Jose Luis Ramirez-GarciaLuna
M. Scott Taylor
Brian Gaerke
Michael H. Weber
Michael H. Weber
Derek H. Rosenzweig
Derek H. Rosenzweig
Lisbet Haglund
Lisbet Haglund
Lisbet Haglund
author_sort Rayan Fairag
collection DOAJ
description Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (β-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive β-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detected via increased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively) in vitro. Furthermore, we evaluated in vivo compatibility, biosafety and bone repair potential in a rat femur window defect model. 100M+β-TCP implants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by μCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.
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spelling doaj.art-7167700d007a4b368d90645b0c64e4032022-12-21T20:13:41ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.654518654518A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and RegenerationRayan Fairag0Rayan Fairag1Rayan Fairag2Li Li3Li Li4Jose Luis Ramirez-GarciaLuna5M. Scott Taylor6Brian Gaerke7Michael H. Weber8Michael H. Weber9Derek H. Rosenzweig10Derek H. Rosenzweig11Lisbet Haglund12Lisbet Haglund13Lisbet Haglund14Department of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, CanadaResearch Institute of McGill University Health Center, Montreal General Hospital, Montreal, QC, CanadaDepartment of Orthopedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, CanadaResearch Institute of McGill University Health Center, Montreal General Hospital, Montreal, QC, CanadaDepartment of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, CanadaPoly-Med Inc., Anderson, SC, United StatesPoly-Med Inc., Anderson, SC, United StatesDepartment of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, CanadaResearch Institute of McGill University Health Center, Montreal General Hospital, Montreal, QC, CanadaDepartment of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, CanadaResearch Institute of McGill University Health Center, Montreal General Hospital, Montreal, QC, CanadaDepartment of Surgery, Division of Orthopaedic Surgery, McGill University, Montreal, QC, CanadaResearch Institute of McGill University Health Center, Montreal General Hospital, Montreal, QC, CanadaShriners Hospital for Children, Montreal, QC, CanadaOrthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (β-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive β-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detected via increased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively) in vitro. Furthermore, we evaluated in vivo compatibility, biosafety and bone repair potential in a rat femur window defect model. 100M+β-TCP implants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by μCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.https://www.frontiersin.org/articles/10.3389/fcell.2021.654518/full3D printingβ-TCPbone repairbone substitutescaffoldcomposite
spellingShingle Rayan Fairag
Rayan Fairag
Rayan Fairag
Li Li
Li Li
Jose Luis Ramirez-GarciaLuna
M. Scott Taylor
Brian Gaerke
Michael H. Weber
Michael H. Weber
Derek H. Rosenzweig
Derek H. Rosenzweig
Lisbet Haglund
Lisbet Haglund
Lisbet Haglund
A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration
Frontiers in Cell and Developmental Biology
3D printing
β-TCP
bone repair
bone substitute
scaffold
composite
title A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration
title_full A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration
title_fullStr A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration
title_full_unstemmed A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration
title_short A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration
title_sort composite lactide mineral 3d printed scaffold for bone repair and regeneration
topic 3D printing
β-TCP
bone repair
bone substitute
scaffold
composite
url https://www.frontiersin.org/articles/10.3389/fcell.2021.654518/full
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