Intra-articular Adenosine, Lidocaine and Magnesium (ALM) solution decreases postoperative joint fibrosis in an experimental knee implant model

Abstract

Abstract Background There is currently no drug therapy to prevent arthrofibrosis following knee surgery. We aimed to determine if the anti-ischemic and anti-inflammatory drug adenosine, lidocaine and Mg2+ (ALM), reduces surgery-related arthrofibrosis in a rat model of knee implant surgery. Methods Male Sprague-Dawley rats (n = 24) were randomly divided into ALM or saline groups. The right knee of each animal was implanted with custom titanium (femur) and polyethylene (tibia) implants, and the left knee served as a non-operated control. An intra-articular ALM or saline bolus (0.1 ml) was administered at the end of surgery, and animals monitored for 4 weeks. Fibrotic changes were assessed by macroscopic examination, histopathology, and expression of key inflammatory and fibrotic markers in the joint capsule and infrapatellar fat pad (IFP). Results Knee swelling was evident in both groups at 4 weeks. However, range of motion was 2-fold higher in the ALM-treated knees, and differences in macroscopic pathology indicated improved healing, compared to the control group. Histologically, ALM treatment also led to significantly decreased synovitis and fibrotic pathology in the joint capsule and IFP compared to saline controls. RNA and protein expression profiles of pro-fibrotic mediators (α-SMA, TGF-β1, FGF1, PDGFA) were also significantly lower in knees from ALM-treated animals. In addition, the expression of inflammatory mediators was lower in plasma (IL-1β, IL-10) and joint tissue (NFκB, IL-1β, IL-12), 4 weeks after surgery. Conclusion We show that intra-articular administration of a single ALM bolus significantly decreased fibrotic pathology and synovitis in an experimental model of knee implant surgery, by blunting inflammation and modulating essential genes of fibrosis. ALM has the therapeutic potential for translation into humans undergoing knee replacement surgery.