Production of a novel cellularised & bioresorbable osteochrondral plug activating mesenchymal stem cells for joint repair.
PhD Supervisor(s): Virginie Sottile; David Grant; Colin Scotchford; Nick Medcalf
Orthopaedic pathologies have a large incidence, a high socio-economic cost and a major impact on the quality of life for sufferers. Although tissue engineering approaches are under way for bone defects, repair of the joint region remains problematic because of its complex structure. Over the last two decades, many innovative stratergies for articular cartilage repair have been proposed; however many have subsequently failed as secure fixation of matrices or constructs to the osteochondral bone could not be achieved under load-bearing conditions. There is therefore a need to develop new tissue constructs spanning the cartilage/bone interface, in order to overcome this problem and provide clinical strategies for joint repair. This project will generate a novel osteochondral model by combining cell progenitors able to form bone and cartilage tissue with novel biomaterials exhibiting dual osteo- and chondro-inductive properties.
Existing models don't reflect the complexity of the bone/joint continuum, where mineralised tissue gradually changes into cartilage matrix. Additionally, the unavailability of optimal scaffolds conveying the graded properties of the tissue has so far limited our ability to engineer 3D-constructs for model and joint repair. to adddress this , we have developed a novel biomaterial construct, which offers a defferential porous structure allowing spatial resolution, in order to mimic the complex integration of bone and cartilage tissue present in the joint. Highly porous, this novel resorbable scaffold offers smaller pores in one end and gradually larger ones towards the other, mirroring the pattern of the native tissue.
Using human mesenchymal stem cells, the precursors of both bone-forming and cartilage-forming cells, we have shown that this new scaffold is cytocompatible, and we have developed unique culture conditions supporting these cells to grow and form bone and cartilage lineages [France 2013 JTERM]. This treatment allows the formation of osteochondral lineages within the 3D construct cultured a single vessel, In addition, we have indentified a stable small moelcule inducer able to enhance the osteo-chondrogenic response of mesenchymal stem cells in 2D culture.
The present project will build on the work to explore the translational potential of the construct around the following milestones:
