1. Summary and Conclusions Peter Roughley

2. Repair Techniques • Current Microfracture – stem cell ACI MACI – articular chondrocyte + stem cell AMIC • Future Chondrocytes from stem cell Source – BM, fat, synovium, cartilage Conditions – TGFbeta, TGFbeta/BMP6 Oxygen – 5% High density Scaffold - Membrane – 2D Matrix – 3D Loading - Cyclic compression Gene therapy - ex vivo in situ

3. Molecular Organization • Endochondral ossification – wnt, PTHRP, Ihh, site 1 proteinase • Matrix – regulated – COMP/collagen integrated – Col6, biglycan, matrillin, Col2, fibromodulin, PRELP, HSPG, cell stable – X-links • Surface - Lubricin Shear loading Lost in OC graft • Degardation - Proteases workhorse, cathepsin K sophisticated – MMPs, ADAMTSs hyaluronidase NO – IL-1 – 5% oxygen

4. Animal Models • None Ideal –quadrupeds – primates (human) Age – cost, young Size – cost, MRI/arthroscopy Cartilage thickness Cartilage cell density Functional assessment – pain Too emotive – dogs, horses, primates • Purpose - Adult onset OA Focal lesions • Predisposition - limb deformity Genetic