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Title: Tissue engineering of an osteochondral transplant by using a cell/scaffold construct
Keywords: Tissue engineering, osteochondral, mesenchymal stem cell
Issue Date: 28-Jun-2009
Citation: HO SAEY TUAN (2009-06-28). Tissue engineering of an osteochondral transplant by using a cell/scaffold construct. ScholarBank@NUS Repository.
Abstract: Traditional clinical remedies are unable to address osteochondral defects adequately.
Given the paucity of available alternatives, the author aims to harness the advances in
stem cell and biomaterial research to create a biphasic osteochondral implant that caters to
both cartilage and bone regeneration. The endeavor was driven by the hypothesis that a
biomechanically competent biphasic scaffold that is seeded with hydrogel encapsulated
Mesenchymal Stem Cells (MSC) would support osteochondral repair. Therefore the aim
would be to select a suitable cartilage hydrogel and to engineer scaffolds which are
mechanically compatible to the native osteochondral tissue. Moreover the design of a
cartilage resurfacing membrane constituted an additional objective. Lastly, the feasibility
of the assembled construct had to be validated in animal models. The investigation
proceeded with a cartilage hydrogel selection. Consequently, fibrin was found to enhance
MSC chondrogenesis, cellular growth and extracellular matrix synthesis in in vitro 3D
osteochondral constructs. This bioactive hydrogel was coupled with rapid prototyped
polycaprolactone b based scaffolds in the reconstruction of critically sized osteochondral
defects in rabbits. These scaffolds were sufficiently porous and they mimicked the
mechanical characteristics of bone and cartilage. In vivo findings indicated bone repair to be facilitated by the open architecture of the scaffolds while cartilage regeneration was
reliant on the implanted MSC and matrix support. However the unsatisfactory healing at
the cartilage surface suggested the inclusion of a membrane that would help to retain the
seeded cells. In that light, the use of polycaprolactone - collagen electrospun meshes were explored. The synthetic membrane demonstrated MSC compatibility in the in vitro chondrogenic environment without inducing a hypertropic response. All these findings have prompted a large animal study with translational objectives. Osteochondral healing in the large animal was enhanced by the use of the implanted MSC within the biphasic
scaffold and the electrospun mesh. However tissue healing was not just dependent on
exogenous factors but also on the endogenous biomechanical features at the defect site.
The research efforts have yielded a functional osteochondral implant with due attention
given to the specific components and the concept was validated in the final preclinical
Appears in Collections:Ph.D Theses (Open)

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