Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds

Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds

In cranial flat bone fractures, spontaneous bone repair will occur only when the fracture ends are in close contact. However, in cases wherein bone discontinuity is extensive, surgical interventions are often required. To this end, autologous bone is harvested and surgically integrated into the site...

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Bibliographic Details
Published in:Journal of tissue engineering Vol. 14; p. 20417314231159740
Main Authors: Carmon, Idan, Kalmus, Shira, Zobrab, Anna, Alterman, Michael, Emram, Raphaelle, Gussarsky, May, Kandel, Leonid, Reich, Eli, Casap, Nardi, Dvir-Ginzberg, Mona
Format: Journal Article
Language:English
Published: London, England SAGE Publications 01-01-2023
Sage Publications Ltd
SAGE Publishing
Subjects:
Blood coagulation
Bone growth
Bone healing
Calvaria
Cancellous bone
Cartilage
Chondrocytes
Collagen
Computed tomography
Defects
Fractures
Histology
Maxillofacial
Mineralization
Morbidity
Original
Osteogenesis
Scaffolds
Serum levels
Skull
critical fracture
Cartilage
BMP2
chondrocytes
graft
scaffold
calvaria
ossification
WISP1
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Summary:In cranial flat bone fractures, spontaneous bone repair will occur only when the fracture ends are in close contact. However, in cases wherein bone discontinuity is extensive, surgical interventions are often required. To this end, autologous bone is harvested and surgically integrated into the site of fracture. Here we propose to use cartilage, as an alternative autologous source, to promote cranial fracture repair. The advantage of this approach is the potential reduction in donor site morbidity, likely due to the avascular and aneural nature of cartilage. As a first step we attempted to induce cartilage mineralization in vitro, using micromass primary chondrocyte cultures, incubated with BMP2 and/or WISP1, which were examined histologically following a 3-week culture period. Next, chondrocyte seeded collagen scaffolds were evaluated in vitro for expression profiles and ALP activity. Finally, chondrocyte-seeded collagen scaffolds were implanted in a Lewis rats 8 mm critical calvaria defect model, which was imaged via live CT for 12 weeks until sacrifice. End points were analyzed for microCT, histology, and serum levels of bone related markers. Micromass cultures exhibited an osseous inducing trend following WISP1 administration, which was maintained in chondrocyte seeded scaffolds. Accordingly, in vivo analysis was carried out to assess the impact of WISP1-pretreated chondrocytes (WCS) versus untreated chondrocytes (UCS) in calvaria defect model and compared to untreated control comprised of a defect-associated blood clot (BC) or empty collagen scaffold (CS) implant. Live CT and microCT exhibited higher mineralization volumes in critical defect implanted with UCS, with some structural improvements in WCS. Histological analysis exhibited higher anabolic bone formation in WCS and trabecular bone was detected in WCS and UCS groups. Chondrocytes implanted into critical cranial defect expedite the formation of native-like osseous tissue, especially after WISP1 priming in culture. Ultimately, these data support the use of autologous chondrocytes to repair critical maxillofacial defects.
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ISSN:2041-7314
2041-7314
DOI:10.1177/20417314231159740