Morris, Jodie L., Letson, Hayley L., McEwen, Peter, Biros, Erik, Dlaska, Constantin, Hazratwala, Kaushik, Wilkinson, Matthew, and Dobson, Geoffrey P. (2021) Intra-articular Adenosine, Lidocaine and Magnesium (ALM) solution decreases postoperative joint fibrosis in an experimental knee implant model. Translational Medicine Communications, 6. 4.

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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.

Item ID:	65941
Item Type:	Article (Research - C1)
ISSN:	2396-832X
Keywords:	total knee arthroplasty; stiffness; arthrofibrosis; inflammation
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Copyright Information:	© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Funders:	Australian Orthopaedic Association Research Foundation (AOA), Townsville Hospital and Health Services Study, Education, Research and Training Fund, Orthopaedic Research Institute of Queensland, James Cook University (JCU)
Date Deposited:	03 Feb 2021 02:43
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320216 Orthopaedics @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920116 Skeletal System and Disorders (incl. Arthritis) @ 100%
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