Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Abstract

Background and PurposeCorticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations.Experimental ApproachThe applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes.Key ResultsIntra‐articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability‐induced OA cartilage degeneration, synovitis, nor the OA‐related bone phenotype was affected. However, biomaterial microsphere‐based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration.Conclusions and ImplicationsWe conclude that short‐term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage‐associated joint instability, but not of brief exposure.

Evaluation of Different Intraarticular Injection Therapies with Gait Analysis in a Rat Osteoarthritis Model

“…49 Studies have shown that IA CS treatment is used in rat OA models, and there is significant relief of pain. 50,51 In our study, IA CS was applied to the second group and IA HA was applied to the third group, and according to the post-OA, run duration, mean stance, paw print length, paw print width, paw print area, stride length, and swing speed recovered significantly. In addition, amelioration was observed in the scores obtained after histological analysis compared to the post-OA scores.…”

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis

“…Moreover, in human tissue, TA inhibited loss of proteoglycans in co-culture of human cartilage tissue with synovium [ 70 ], and in equine cartilage stimulated with IL-1β decreased COX-2 and matrix metalloproteinase gene expression [ 71 ]. However, prolonged intra-articular exposure of TA in joints with acute trauma must be avoided, as it has been found to exacerbate joint instability and associated joint degeneration in an experimental model [ 26 ].…”

“…Empty nor TA-PEAMs influenced articular cartilage quality [ 12 ]. However, in a rat model of instability-induced OA, local microspheres-based release of TA was shown to aggravate disease, which was not seen in the animals treated with bolus injection nor in healthy joints injected with TA-loaded PEAMs, indicating that the prolonged exposure to TA in combination with joint trauma was the cause [ 26 ]. Moreover, TA inhibited cell outgrowth from tissue, indicating a possible effect on tissue healing [ 26 ].…”

Association between Oncostatin M Expression and Inflammatory Phenotype in Experimental Arthritis Models and Osteoarthritis Patients

“…Animals were euthanized after 6 weeks with CO 2 . For the ACLT model, OA was induced unilaterally through anterior cruciate ligament transection and partial medial meniscectomy in the left knee of 6 rats that were randomly taken from their cages, under general isoflurane anesthesia [31]. After 16 weeks, rats were euthanized with CO 2 .…”