Spontaneous In Vivo Regeneration of the Articular Cartilage Using a Novel Double-Network Hydrogel

Abstract

It has been a commonly established concept that articular (hyaline) cartilage tissue cannot spontaneously regenerate in vivo. We have challenged this concept by using a plug created with an originally developed double-network (DN) gel—consisting of poly-(2-acrylamido-2-methylpropanesulfonic acid; PAMPS) and poly-(N,N′-dimethyl acrylamide; PDMAAm)—into a large osteochondral defect in a rabbit patellofemoral joint. The defect was made so that it intentionally remained with a depth of 1 to 3 mm after surgery. At 4 weeks, cartilage tissue rich in proteoglycan and type 2 collagen had regenerated in the defect. In cells of the regenerated tissue, type 2 collagen, Aggrican, and SRY (sex determining region Y)-box 9 (SOX9) mRNAs were highly expressed. On the other hand, cartilage regeneration was rarely found in a defect without any treatment. We conclude that spontaneous regeneration of the articular cartilage can be induced in vivo in an osteochondral defect by implanting a PAMPS/PDMAAm DN gel plug into the bottom of the cavity, leaving the defect itself vacant. This finding suggests a significant modification of the above commonly eslablished concept. Also, the findings of this study have prompted an innovative strategy in the field of joint surgery, to repair an osteochondral defect using an advanced high-function gel. Concerning the mechanism of the spontaneous cartilage regeneration, we speculate that the bioactive DN gel may have the potential to induce the differentiation of mesenchymal stem cells contained in the blood clot into chondrocytes.