Induction of Spontaneous Hyaline Cartilage Regeneration Using a Double-Network Gel

Abstract

Background: A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N′-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. Purpose: To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Study Design: Controlled laboratory study. Methods: A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O’Driscoll et al. Results: The DN gel–implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel–implanted defects compared with the untreated control at each period ( P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel–implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks ( P = .0106), while there was no statistical difference between the DN gel–implanted and normal knees. Conclusion: This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. Clinical Relevance: This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.