"Traditionally, tissue engineering strategies employ a “top-down” approach, where cells are randomly seeded in polymeric scaffolds or hydrogels. As a result, engineered tissues are often at best homogenous in composition, lacking the morphological or structural features of native tissues. Alternative “bottom-up” approaches, that leverage the self-organizing capacity of stem cells, have shown promise for engineering human tissues . During early limb development stem cells aggregate and condensate before differentiating along a chondrogenic lineage. In fact, pellet culture, where mesenchymal stem cells (MSCs) are forced to aggregate using centrifugation, has been the standard culture system for initiation of stem cell chondrogenesis in vitro as it allows cell-cell interactions that are analogous to those that occur during pre-cartilage condensation during early joint development . Therefore cellular aggregates, microtissues or organoids might represent promising biological building blocks for the engineering of functional tissues.
This talk will describe how phenotypically distinct microtissues generated from stem/stromal cells can be integrated to engineer a biphasic osteochondral implant containing a biomimetic layer of engineered articular cartilage. The osseous region of this osteochondral graft was engineered using islands of hypertrophic cartilage microtissues capable of executing an endochondral programme, while the chondral region of the graft was formed by the self-organisation of early-cartilage microtissues into a unified and structurally organised tissue mimetic of native AC. Furthermore this talk will examine whether implantation of such an engineered plug into critically-sized caprine osteochondral defects can result in effective biological joint resurfacing and prevent the deleterious cascade of events that typically follow an untreated osteochondral injury.
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