A Hyperosmolar Saline Solution Fortified with Anti-Inflammatory Components Mitigates Articular Cartilage Pro-Inflammatory and Degradative Responses in an In Vitro Model of Knee Arthroscopy

Abstract

Objective To evaluate differences in pro-inflammatory and degradative mediator production from osteoarthritic knee articular cartilage explants treated with a hyperosmolar saline solution supplemented with anti-inflammatory components (l-glutamine, ascorbic acid, sodium pyruvate, epigallocatechin gallate [EGCG], and dexamethasone) or normal saline using an in vitro model for knee arthroscopy. Design Full-thickness 6 mm articular cartilage explants ( n = 12/patient) were created from femoral condyle and tibial plateau samples collected from patients who received knee arthroplasty. One explant half was treated for 3 hours with hyperosmolar saline (600 mOsm/L) supplemented with anti-inflammatory components and the corresponding half with normal saline (308 mOsm/L). Explants were cultured for 3 days and then collected for biomarker analyses. Media biomarker concentrations were normalized to the wet weight of the tissue (mg) and were analyzed by a paired t test with significance set at P < 0.05. Results Cartilage was collected from 9 females and 2 males (mean age = 68 years). Concentrations of MCP-1 ( P < 0.001), IL-8 ( P = 0.03), GRO-α ( P = 0.02), MMP-1 ( P < 0.001), MMP-2 ( P < 0.001), and MMP-3 ( P < 0.001) were significantly lower in explant halves treated with the enhanced hyperosmolar solution. When considering only those cartilage explants in the top tercile of tissue metabolism, IL-6 ( P = 0.005), IL-8 ( P = 0.0001), MCP-1 ( P < 0.001), GRO-α ( P = 0.0003), MMP-1 ( P < 0.001), MMP-2 ( P < 0.001), MMP-3 ( P < 0.001), and GAG expression ( P = 0.0001) was significantly lower in cartilage explant halves treated with the enhanced hyperosmolar solution. Conclusions Treatment of cartilage explants with a hyperosmolar saline arthroscopic irrigation solution supplemented with anti-inflammatory components was associated with significant decreases in inflammatory and degradative mediator production and mitigation of proteoglycan loss.

Making the Case for Hyperosmolar Saline Arthroscopic Irrigation Fluids: A Systematic Review of Basic Science, Translational, and Clinical Evidence

“…42 Furthermore, hyperosmolar solutions may also beneficially influence the expression of proinflammatory and degradative mediators, affording another mechanism for chondroprotection. 29,31 Translational canine and equine studies verify the safety of hyperosmolar irrigation solutions for use in arthroscopic surgery and provide some evidence in support of potential clinical benefits as well. Chondrocyte viability and articular cartilage water content were maintained in both animal model studies when hyperosmolar irrigation solutions (600 mOsm/L) were used for canine shoulder or equine stifle arthroscopy.…”

“…Similarly, this research group also evaluated the impact of a hyperosmolar saline solution supplemented with anti-inflammatory components. 31 The researchers compared the differences in pro-inflammatory and degradative mediator production from osteoarthritic knee articular cartilage explants treated with either this supplemented hyperosmolar saline solution or isotonic saline. The hyperosmolar saline solution tested in this study consisted of a 1.8% saline solution that was created by adding 165 ml of 7.2% saline to 1L of 0.9% saline.…”

“…During arthroscopic procedures, a continuous flow of irrigation solution is required to our research. [27][28][29][30][31] Therefore, we sought to systematically review and synthesize previously published basic science, translational, and clinical studies on the use of hyperosmolar arthroscopic irrigation fluids in order to delineate the optimal fluid for clinical use.…”

“…While prior studies have focused on modifying factors such as fluid type, pH, and temperature, [20][21][22][23][24][25][26] hyperosmolar irrigation solutions have been the focus of our research. [27][28][29][30][31] Therefore, we sought to systematically review and synthesize previously published basic science, translational, and clinical studies on the use of hyperosmolar arthroscopic irrigation fluids in order to delineate the optimal fluid for clinical use.…”

Response of Articular Cartilage to Hyperosmolar Stress: Report of an Ex Vivo Injury Model

“…To ensure comparability with previous studies, the hyperosmolar saline group was defined at an osmolarity of 600 mOsm, equivalent to a 1.8% saline solution. 2,5,13,14,16,20,[25][26][27] Osmolality was checked and adjusted using a freezing point osmometer (Mikro-Osmometer 210; Fiske) and then filtered to ensure sterility. Note that 0.9% saline has a calculated osmolarity of 308 mOsm/L, whereas the actual osmolality is lower and was measured precisely at 286 mOsm/kg.…”