Abstract
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.
Highlights
Large mandibular defects originating from trauma and tumor ablative surgeries cause great suffering to patients due to compromised appearance and interruption of masticatory function and articulation
The present study aimed to explore the feasibility of customized prefabricated tissueengineered bones (PTEB) constructs over directly implanted scaffolds toward faster recovery of mandibular bone defects
PLGA/TCP and TCP scaffolds were successfully fabricated by LTRP and robocasting, respectively
Summary
Large mandibular defects originating from trauma and tumor ablative surgeries cause great suffering to patients due to compromised appearance and interruption of masticatory function and articulation. Vascularized autografts, such as fibular flaps, iliac bone graft, etc., are routinely used for mandibular reconstruction.[1] donor site morbidity and difficulty in rehabilitating complex geometry and/or occlusal function of human mandible are still problems. Conventional cell-based tissue engineered constructs seem to be compromised in repairing large bone defects due to limited vascularization and lack of a mature vasculature network, which are crucial for providing adequate nutrient and oxygen supply to the adhered/migrated cells beyond 200 μm from the nearest blood capillary.[2] In these studies, a stable blood supply could be established in prefabricated tissueengineered bones (PTEB) through endocultivation in a highly vascularized muscle pocket. Bone overgrowth of PTEB was a serious problem, requiring further modification of PTEB to shape it before performing a reparative surgery.[6,7] The advent of 3D printed metal, ceramic, polymer, as well as Received: April 18, 2021 Accepted: November 15, 2021 Published: November 22, 2021
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