Engineered cartilage heals skull defects.
BACKGROUND
The purposes of this study were to differentiate embryonic limb bud cells into cartilage, characterize the nodules produced, and determine their ability to heal a mouse skull defect.


METHODS
Aggregated mouse limb bud cells (E12-E12.5), cultured in a bioreactor for 3 weeks, were analyzed by histology or implanted in 6 skull defects. Six controls had no implants. The mice were scanned with microcomputed tomography weekly. At 2 and 4 weeks, a mouse from each group was killed, and the defect region was prepared for histology.


RESULTS
Chondrocytes in nodules were mainly hypertrophic. About 90% of the nodules mineralized. BrdU staining showed dividing cells in the perichondrium. Microcomputed tomography scans showed increasing minerals in implanted nodules that completely filled the defect by 6 weeks; defects in the control mice were not healed by then. At 2 and 4 weeks, the control skull sections showed only a thin bony layer over the defect. At 2 weeks, bone and cartilage filled the defects with implants, and the implants were well integrated with the adjacent cortical bone. At 4 weeks, the implant had turned almost entirely into bone.


CONCLUSIONS
Cartilage differentiated in the bioreactor and facilitated healing when implanted into a defect. Engineering cartilage to replace bone is an alternative to current methods of bone grafting.
Lan
L
Doan
Connor
C
Kelley
Heather
H
Luong
Jeryl
J
English
Hector
H
Gomez
Evan
E
Johnson
Dianna
D
Cody
Pauline Jackie
PJ
Duke
D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D002356:Cartilage / Q000166:cytology / Q000637:transplantation*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis; D053595:Embryonic Stem Cells / Q000166:cytology; D020007:Implants, Experimental; D018878:Limb Buds / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D016348:Osseointegration / Q000502:physiology*; D010027:Osteotomy; D012886:Skull / Q000601:surgery; D023822:Tissue Engineering / Q000379:methods*