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Intra-articular injection of N-acetylglucosamine and hyaluronic acid combined with PLGA scaffolds for osteochondral repair in rabbits

机译:关节腔内注射N-乙酰氨基葡萄糖和透明质酸联合PLGA支架在兔骨软骨修复中的应用

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摘要

Repairing damaged articular cartilage is particularly challenging because of the limited ability of cartilage to perform self-repair. Intra-articular injections of N-acetylglucosamine (GlcNAc) comprise a method of repairing full-thickness articular cartilage defects in the rabbit knee joint model. To date, the effects of administration of GlcNAc and hyaluronic acid (HA) have been investigated only in the context of osteoarthritis treatment. Therefore, we evaluated the therapeutic effects of using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants and intra-articular injections of GlcNAc or HA in a rabbit model of osteochondral regeneration to investigate whether they have the potential for inducing osteochondral regeneration when used alone or simultaneously. Twenty-four rabbits were randomized into one of four groups: the scaffold-only group (PLGA), the scaffold with intra-articular injections of GlcNAc (PLGA+G) group, twice per week for four weeks; the scaffold with intra-articular injections of HA group (PLGA+HA) group, once per week for three weeks; and the scaffold with intra-articular injections of GlcNAc and HA (PLGA+G+HA) group, once per week for three weeks. Knees were evaluated at 4 and 12 weeks after surgery. At the end of testing, only the PLGA+G+HA group exhibited significant bone reconstruction, chondrocyte clustering, and good interactions with adjacent surfaces at 4 weeks. Additionally, the PLGA+G+HA group demonstrated essentially original hyaline cartilage structures that appeared to have sound chondrocyte orientation, considerable glycosaminoglycan levels, and reconstruction of the bone structure at 12 weeks. Moreover, the PLGA+G+HA group showed organized osteochondral integration and significantly higher bone volume per tissue volume and trabecular thickness. However, there were no significant differences between the PLGA+G and PLGA+HA groups except for gap formation on subchondral bone in the PLGA+G group. This study demonstrated that PLGA implantation combined with intra-articular injections of GlcNAc and HA allowed for cartilage and bone regeneration and significantly promoted osteochondral regeneration in rabbits without supplementation of exogenous growth factors. And the combination of this two supplements with PLGA scaffold could also prolong injection interval and better performance than either of them alone for the reconstruction of osteochondral tissue in the knee joints of rabbits.
机译:由于软骨执行自我修复的能力有限,修复受损的关节软骨特别具有挑战性。关节内注射N-乙酰氨基葡萄糖(GlcNAc)包括一种修复兔膝关节模型中全厚度关节软骨缺损的方法。迄今为止,仅在骨关节炎治疗的背景下研究了施用GlcNAc和透明质酸(HA)的效果。因此,我们评估了在兔骨软骨再生模型中使用无细胞的多孔聚乳酸-乙醇酸-乙醇酸(PLGA)移植物和关节腔内注射GlcNAc或HA的治疗效果,以研究它们是否具有诱导单独或同时使用骨软骨再生。 24只兔随机分为四组之一:仅支架组(PLGA),关节腔内注射GlcNAc的支架(PLGA + G)组,每周两次,共4周;每组4只。 HA组(PLGA + HA)关节腔内注射支架,每周一次,共3周;每周一次的GlcNAc和HA(PLGA + G + HA)组进行关节腔内注射,持续3周。在手术后4和12周对膝盖进行评估。在测试结束时,只有PLGA + G + HA组在4周时显示出明显的骨重建,软骨细胞聚集以及与相邻表面的良好相互作用。另外,PLGA + G + HA组显示出基本原始的透明软骨结构,在12周时似乎具有良好的软骨细胞定向,相当高的糖胺聚糖水平以及骨骼结构的重建。此外,PLGA + G + HA组表现出有组织的骨软骨整合,并且每组织体积和小梁厚度的骨量明显更高。但是,PLGA + G组和PLGA + HA组之间没有显着差异,除了PLGA + G组在软骨下骨上形成间隙。这项研究表明,PLGA植入结合GlcNAc和HA的关节腔内注射可实现软骨和骨骼再生,并显着促进兔的软骨软骨再生,而无需补充外源性生长因子。并且这两种补品与PLGA支架的组合也可以延长注射间隔,并且比单独使用任何一种在兔膝关节的骨软骨组织重建中都有更好的性能。

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