Tissue engineering of an osteochondral transplant by using a cell/scaffold construct

Abstract

Traditional clinical remedies are unable to address osteochondral defects adequately.<br>Given the paucity of available alternatives, the author aims to harness the advances in<br>stem cell and biomaterial research to create a biphasic osteochondral implant that caters to<br>both cartilage and bone regeneration. The endeavor was driven by the hypothesis that a<br>biomechanically competent biphasic scaffold that is seeded with hydrogel encapsulated<br>Mesenchymal Stem Cells (MSC) would support osteochondral repair. Therefore the aim<br>would be to select a suitable cartilage hydrogel and to engineer scaffolds which are<br>mechanically compatible to the native osteochondral tissue. Moreover the design of a<br>cartilage resurfacing membrane constituted an additional objective. Lastly, the feasibility<br>of the assembled construct had to be validated in animal models. The investigation<br>proceeded with a cartilage hydrogel selection. Consequently, fibrin was found to enhance<br>MSC chondrogenesis, cellular growth and extracellular matrix synthesis in in vitro 3D<br>osteochondral constructs. This bioactive hydrogel was coupled with rapid prototyped<br>polycaprolactone b based scaffolds in the reconstruction of critically sized osteochondral<br>defects in rabbits. These scaffolds were sufficiently porous and they mimicked the<br>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<br>reliant on the implanted MSC and matrix support. However the unsatisfactory healing at<br>the cartilage surface suggested the inclusion of a membrane that would help to retain the<br>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<br>scaffold and the electrospun mesh. However tissue healing was not just dependent on<br>exogenous factors but also on the endogenous biomechanical features at the defect site.<br>The research efforts have yielded a functional osteochondral implant with due attention<br>given to the specific components and the concept was validated in the final preclinical<br>model.