Hyaluronic Acid Scaffolds and Injectable Gels for Healing of Induced Arthritis in Rat Knee: Effect of Prednisolone Revisited

Abstract

Considering the absence of a definite cure for osteoarthritis and problems of existing approaches, designing scaffolds for cartilage regeneration by tissue engineering methods seems necessary. Optimization of scaffolds properties is one of the biggest challenges in this area. Due to contradicting reports regarding efficacy and safety of intra-articular injections of corticosteroids, further evaluation of these agents by their incorporation into a designed scaffold could be beneficial. On this basis, a hyaluronic acid (HA) scaffold was designed in two forms: shear-thinning injectable gel and lyophilized implantable disk. Polyethylene glycol diglycidyl ether (PEGDGE) was used as cross-linker. After optimization of scaffolds properties, in vivo efficacy of the most optimum formulation (HA 2%, PEGDGE 0.5%) in the presence and absence of prednisolone (0.1% W/V) was evaluated. In vivo studies in rats showed that after 10 weeks, HA scaffolds, in both forms, repaired damaged articular cartilage to some extent but incorporation of prednisolone into the scaffold showed no additional benefit. Overall it seems that implantable scaffolds of HA could be a potential therapeutic choice for cartilage regeneration and corticosteroids in long term may also reverse these beneficial effects. Hyaluronic acid (HA) is one of the major components of the extracellular matrix and cartilage tissue. There are numerous reports on the efficacy of different scaffolds of HA for cartilage regeneration. New engineering methods focus on retaining the scaffolds in the site for long time as well as loading therapeutic agents to accelerate the healing process. In situ injection of corticosteroids is one of the routine interventions for osteoarthritis. Here, the effect of loading prednisolone as an anti-inflammatory agent into the shear thinning gels and implantable disks of HA for treatment of an induced arthritis in rat knee was revisited. In future studies we will upgrade the scaffold by mixing HA with some other biopolymers to increase the strength and retention of the system and to improve drug loading capacity. It seems that loading specific growth factors would be an alternative to corticosteroids with higher efficacy and lower side effects.