Engineering osteochondral constructs through spatial regulation of endochondral ossification.
Citation:
Sheehy EJ, Vinardell T, Buckley CT, Kelly DJ, Engineering osteochondral constructs through spatial regulation of endochondral ossification., Acta biomaterialia, 9, 3, 2013, 5484-5492Download Item:
Abstract:
Chondrogenically primed bone marrow derived mesenchymal stem cells (MSCs) have been
shown to become hypertrophic and undergo endochondral ossification when implanted in
vivo. Modulating this endochondral phenotype may be an attractive approach to engineering
the osseous phase of an osteochondral implant. The objective of this study was to engineer an
osteochondral tissue by promoting endochondral ossification in one layer of a bi-layered
construct and stable cartilage in the other. The top-half of bi-layered agarose hydrogels were
seeded with culture expanded chondrocytes (termed chondral layer) and the bottom half of
the bi-layered agarose hydrogels with MSCs (termed osseous layer). Constructs were cultured
in a chondrogenic medium for 21 days and thereafter were either maintained in a
chondrogenic medium, transferred to a hypertrophic medium, or implanted subcutaneously
into nude mice. This structured chondrogenic bi-layered co-culture was found to enhance
chondrogenesis in the chondral layer, appearing to help re-establish the chondrogenic
phenotype that is lost in chondrocytes during monolayer expansion. Furthermore, the bilayered
co-culture appeared to suppress hypertrophy and mineralisation in the osseous layer.
The addition of hypertrophic factors to the media was found to induce mineralisation of the
osseous layer in vitro. A similar result was observed in vivo where endochondral ossification
was restricted to the osseous layer of the construct leading to the development of an
osteochondral tissue. This novel approach represents a potential new treatment strategy for
the repair of osteochondral defects.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
Author's Homepage:
http://people.tcd.ie/kellyd9http://people.tcd.ie/cbuckle
Description:
PUBLISHED
Author: KELLY, DANIEL; BUCKLEY, CONOR
Type of material:
Journal ArticleSeries/Report no:
Acta biomaterialia9
3
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Full text availableSubject (TCD):
Next Generation Medical DevicesDOI:
http://dx.doi.org/10.1016/j.actbio.2012.11.008Metadata
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