Hyaluronic acid sheet transplantation attenuates infrapatellar fat pad fibrosis and pain in a rat arthritis model

Fibrosis of the infrapatellar fat pad (IFP) occurs after knee joint surgery or during knee osteoarthritis (KOA) and causes persistent pain and limited mobility. Previous studies demonstrated that treating IFP fibrosis alleviated pain in animal models. In this study, we examined the effects of hyaluronic acid (HA) sheet transplantation on IFP fibrosis and articular cartilage degeneration in a monoiodoacetic acid (MIA) rat arthritis model (95 male rats). Rats received bilateral intra-articular MIA injections (1.0 mg/30 μL) and underwent surgery 4 days later. HA sheets were transplanted on the right knee of each rat (HA group), with the left knee receiving sham surgery (sham group). Incapacitance tests were performed at multiple time points up to 28 days after MIA injection. Macroscopic, histological, and immunohistochemical analyzes were performed 14 and 28 days after injection. The concentrations of HA and interleukin-1β (IL-1β) in the synovial fluid were measured using ELISA. Transplantation of HA sheets could alleviate persistent pain 10-28 days after injection. The HA sheets inhibited articular cartilage degeneration at 14 days. Fibrosis and the invasion of calcitonin gene-related peptide-positive nerve fiber endings in the IFP were inhibited at both 14 and 28 days. Moreover, the HA sheets remained histologically until 10 days after transplantation. The concentration of HA reached its peak on Day 10 after transplantation; the concentration of IL-1β in the sham group was significantly higher than that in the HA group on Day 7. Therefore, HA sheets could be a promising option to treat IFP fibrosis occurring in KOA and after knee joint surgery.