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

Abstract

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.

Molecular mechanisms detected in yak lung tissue via transcriptome-wide analysis provide insights into adaptation to high altitudes

“…BAT is essential for animals under cold plateau conditions, which is a hot area of research on the plateau animals adapt to the cold environment in the plateau area. PPAR is a key regulator of BAT cell differentiation and heat production 32 . The PPAR signaling pathway can promote the differentiation of mesenchymal progenitor cells into BAT cells, helping to produce heat and increase energy consumption.…”

Hyaluronic acid as an adjunct to microfracture in the treatment of osteochondral lesions of the talus: a systematic review of randomized controlled trials

“…In other studies, HA has been shown as a promising treatment modality in osteoarthritis, and osteochondral lesions of the knee by reducing VAS and increasing function in human studies [ 14 , 38 , 53 – 55 ]. Also, there has been evidence in animal models of higher quality hyaline cartilage being generated after osteochondral lesions when scaffolds were combined with HA [ 32 – 34 ], which may lead to a longer-term relief of pain and potential decrease for progression of arthritis when compared to fibrocartilage generated from traditional microfracture alone, especially in obese patients [ 7 ].…”

“…Recommended improvements for future studies in this area would be the blinding of observers, and assessing patients at later follow-up periods. Longer-term follow-up is particularly important to assess the durability of HA and MF as basic science evidence has shown the potential for high-quality hyaline cartilage generation by MF coupled with HA versus the lower quality generated fibrocartilage by MF alone [ 32 – 34 ]. Additional examinations to assess the quality of repair tissue and regeneration of hyaline cartilage would provide more information regarding the actions of HA, alone or in combination with other biological treatments, in cartilage regeneration.…”

The Formulation of the N-Acetylglucosamine as Nanoparticles Increases Its Anti-Inflammatory Activities: An In Vitro Study

“…To improve delivery and distribution, GlcNAc has been intra-articular injected in a rabbit model of OA, using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants. The results showed that the acetyl-aminosugar promoted the repair of full-thickness articular cartilage defects in the animal joints and that the effect is prolonged or increased when a combination of compounds was used [ 23 ]. Moreover, GlcNAc has been shown to exert anti-inflammatory activity and the ability, albeit of limited potency, in stimulating the synthesis of certain factors whose degradation is associated with OA.…”