PROJECT SUMMARY This multi-PI proposal is a collaboration among tissue engineers and an orthopaedic surgeon to develop a liquid cartilage filler, called chondrogel, that would be efficacious in repairing gouge and focal defects of the knee using an arthroscopy approach. Chondrogel is formed using extensively passaged, allogeneic rib chondrocytes that have retained their ability to form mechanically robust neocartilage that is phenotypically akin to articular cartilage (e.g., production of collagen II and lubricin, absence of collagen I and X). Preliminary data show that chondrogel fills gouge defects in explant culture and also in vivo after 16wks in the minipig knee. We have also developed arthroscopic techniques for the minipig. In this proposal, we will show that, in addition to gouge defects, chondrogel will be effective in healing focal defects as well when administered arthroscopically. This will be achieved in two aims. In Aim 1, we will examine chondrogel 1) to show that, in addition to 20x1mm gouge defects, chondrogel is capable of filling focal defects 5mm in dia. in explant culture (Aim 1, Phase I), and 2) to find the maximum arthroscopic intraarticular pressure where chondrogel is still retained in gouge and focal defects (Aim 1, Phase II). In Aim 2, we will determine if chondrogel heals gouge and focal articular cartilage defects in the minipig using arthroscopy. Because chondrogel has been designed based on surgeon surveys and because it is based on rigorous science demonstrating its ability to form cartilage, successful completion of this proposal would allow the use of arthroscopy to treat cartilage defects.