ORIGINAL RESEARCH Hyaluronic Acid Scaffolds and Injectable Gels for Healing of Induced Arthritis in Rat Knee: Effect of Prednisolone Revisited Farhad Mohammadi 1 & Azad Vosough 1 & Nader Tanideh 2 & Soliman Mohammadi Samani 1 & Fatemeh Ahmadi 1 Received: 1 November 2019 /Revised: 12 March 2020 /Accepted: 24 March 2020 # The Regenerative Engineering Society 2020 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 prednis- olone 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. Lay Summary 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. Keywords Cartilage regeneration . Hyaluronic acid . Implantable disks . Injectable gels . Prednisolone Introduction Degenerative cartilage disease, also referred to as “osteoarthri- tis” is associated with pain and disability. Many people spe- cially those at ages 60 and over have some degree of osteoarthritis (OA) [1]. Cartilage repair is slow and limited due to poor blood supply and also because of slow metabolism and immobility of chondrocytes which are the only cells in this tissue [2, 3]. Treating cartilage defects with methods such as perichon- drium transplantation, debridement, mosaicplasty etc. has varying success rates, and such treatments usually have no satisfactory results in the long term [4]. The main reason for failure of these treatment strategies is that the newly formed tissue lacks the structural organization of cartilage and has weaker mechanical properties compared with native tissue [5]. Another therapeutic choice which is far more accepted and used clinically is intra-articular injections of hyaluronic acid (HA) and corticosteroids. * Fatemeh Ahmadi ahmadi_f@sums.ac.ir 1 Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran 2 Department of Pharmacology, Stem Cell and Transgenic Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Regenerative Engineering and Translational Medicine https://doi.org/10.1007/s40883-020-00158-y