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

Date Published: December 31, 2018

Publisher: Public Library of Science

Author(s): Hsueh-Chun Wang, Yi-Ting Lin, Tzu-Hsiang Lin, Nai-Jen Chang, Chih-Chan Lin, Horng-Chaung Hsu, Ming-Long Yeh, Jorge S. Burns.


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.

Partial Text

Osteochondral defect (OCD), a type of joint disorder that often occurs with disease or repetitive trauma in the bone, cartilage, and bone–cartilage interface [1]. Left untreated, it may progress to degenerative osteoarthritis (OA) with disability and function loss. Current clinical treatments for cartilage repair include hyaluronan injection, microfracture, bone marrow stimulation, mosaicplasty as autologous osteochondral transplantation, and autologous chondrocyte implantation. Nevertheless, problems exist such as donor site morbidity, poor integration with host tissue, fibrocartilage formation, and chondrocyte dedifferentiation [2–5]. Therefore, tissue engineering has emerged and may offer significant advantages compared with traditional clinical treatment methods. Cells, scaffolds, and signals are three important factors involved in tissue engineering. Regarding the scaffold, cell-free and cell-seeded scaffolds are two approaches that are typically used; however, the cell-free method is often adopted due to needless of cell expansion and less time-consumption. Ideal scaffolds should provide mechanical support and guide cell adhesion, proliferation, and/or differentiation to regenerate osteochondral tissue. Poly lactic-co-glycolic acid (PLGA) is a synthetic material and the copolymer of polylactic acid and polyglycolic acid [6]. This implant possesses superior mechanical strength [7] compared to naturally derived materials and provides a provisional matrix for osteochondral regeneration [8, 9]. PLGA is a safe biomaterial for clinical applications [10] that has been approved by the United States Food and Drug Administration [11, 12].

In summary, we demonstrated that acellular PLGA scaffolds combined with intra-articular injections of GlcNAc and HA could accelerate osteochondral regeneration in rabbits. The three-dimensional acellular and porous PLGA scaffolds enhanced osteochondral regeneration and provided the rigidity to withstand the strength of compression loading at the weight-bearing site.