Morris, Jodie L., Letson, Hayley L., McEwen, Peter C., and Dobson, Geoffrey P. (2024) Adenosine, lidocaine, and magnesium therapy augments joint tissue healing following experimental anterior cruciate ligament rupture and reconstruction. Bone & Joint Research, 13 (6). pp. 279-293.

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Abstract

Aims: Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods: Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.

Results: Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased.

Conclusion: At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials.

Item ID:	82958
Item Type:	Article (Research - C1)
ISSN:	2046-3758
Keywords:	anterior cruciate ligament, ACL, knee, reconstruction, adenosine, lidocaine, magnesium, ALM
Copyright Information:	© 2024 Morris et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/
Funders:	US Department of Defense (USAMRAA Award)
Projects and Grants:	Award No. W81XWH-20-1-0931. Log No. OR190008
Date Deposited:	11 Jun 2024 21:56
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320216 Orthopaedics @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 70% 20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 30%
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