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BackgroundThe current surgical procedure of choice for lumbar intervertebral disc (IVD) herniation is discectomy. However, defects within IVD produced upon discectomy may impair tissue healing and predispose patients to subsequent IVD degeneration. This study aimed to investigate whether the use of an acellular bioresorbable ultra-purified alginate (UPAL) gel implantation system is safe and effective as a reparative therapeutic strategy after lumbar discectomy.MethodsHuman IVD cells were cultured in a three-dimensional system in UPAL gel. In addition, lumbar spines of sheep were used for mechanical analysis. Finally, the gel was implanted into IVD after discectomy in rabbits and sheep in vivo.FindingsThe UPAL gel was biocompatible with human IVD cells and promoted extracellular matrix production after discectomy, demonstrating sufficient biomechanical characteristics without material protrusion.InterpretationThe present results indicate the safety and efficacy of UPAL gels in a large animal model and suggest that these gels represent a novel therapeutic strategy after discectomy in cases of lumbar IVD herniation.FundGrant-in-Aid for the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

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Mosaicplasty for advanced lesions of capitellar osteochondritis dissecans in teenaged baseball players can provide satisfactory clinical and radiographic results.

In this study, we successfully developed three-dimensional scaffolds fabricated from the chitosan-based hyaluronic acid hybrid polymer fibers, which can control the porous structure. To determine the adequate pore size for enhancing the chondrogenesis of cultured cells, we compared the behaviors of rabbit chondrocytes in scaffolds comprising different pore sizes (100, 200, and 400 microm pore size). Regarding the cell proliferation, there was no significant difference among the three groups. On the other hand, glycosaminoglycan contents in the 400 microm group significantly increased during the culture period, compared with those in the other groups. The ratio of type II to type I collagen mRNA level was also significantly higher in the 400 microm group than in the other groups. These results indicate that our scaffold with 400 microm pore size significantly enhances the extracellular matrix synthesis by chondrocytes. Additionally, the current scaffolds showed high mechanical properties, compared with liquid and gel materials. The data derived from this study suggest great promise for the future of a novel fabricated material with relatively large pore size as a scaffold for cartilage regeneration. The biological and mechanical advantages presented here will make it possible to apply our scaffold to relatively wide cartilaginous lesions.

We developed a novel cellular implantation system using an in situ forming ultra-purified alginate gel with quite low endotoxity. The aims of this study were to determine the superiority of chondrogenic potential of bone marrow stromal cells (BMSCs) cultured in the purified alginate gel compared with a commercial grade gel, and to assess reparative tissues treated with BMSCs implanted using the developed system into cartilage defects in rabbit knees. The effects of each alginate gel on cellular proliferation and chondrogenesis of rabbit BMSCs were determined by in vitro assessments. Using our purified alginate gel, a novel vehicle system for injecting BMSCs into osteochondral defects without periosteal patch was successfully established in this animal models. The in vitro analyses demonstrated that the purification of alginate significantly enhanced the cellular proliferation and chondrogenic differentiation of BMSCs. The in vivo assessments suggested that the implantation of BMSCs with the developed system using the purified alginate gel histologically and mechanically improved the reparative tissue of osteochondral defects. This system using the purified alginate gel shows the clinical potential for arthroscopically injectable implantation of BMSCs for the treatment of cartilaginous lesions.

The ideal cell-carrier material for cartilage regeneration should be one that closely mimics the natural environment in a living articular cartilage matrix. In the current study, we considered that alginate-based chitosan hybrid biomaterials could provide excellent supports for chondrocyte adhesion. To test this hypothesis, we investigated the adhesion behavior of rabbit chondrocytes onto an alginate polymer versus the adhesion of the chondrocytes onto some alginate-based chitosan hybrid polymer fibers in vitro. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with chondrocytes in comparison with alginate polymer fiber. Additionally, morphologic studies revealed maintenance of the characteristic round morphology of the chondrocyte and the dense fiber of the type II collagen produced by the chondrocytes in the hybrid polymer. On the basis of these results, we conclude that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial for cartilage tissue scaffolds.