Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1

Abstract

Objective: Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions.

Experimental design: Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4h/day at 1 Hz and 0%-26% strain for 14 days in the presence of 0 or 100 pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed.

Results: IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair.

Conclusions: Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions.

Fig. 1

Matrix metalloproteinase (MMP) activity in the media of meniscal repair model explants that were exposed to no strain, strain, no strain + IL-1, or strain + IL-1. The strains tested were 1% (top panel), 10% (middle panel), and 26% (bottom panel). The MMP activity is expressed as fluorescence units (FU) per mg wet weight + standard error. *: p < 0.05 compared to all other treatments.

Fig. 2

ADAMTS-4 activity in the media of meniscal repair model explants that were exposed to no strain, strain, no strain + IL-1, or strain + IL-1. The strains tested were 1% (top panel), 10% (middle panel), and 26% (bottom panel). The aggrecanase activity is expressed as fluorescence units (FU) per mg wet weight + standard error.

Fig. 3

Sulfated glycosaminoglycan (S-GAG) release into the media of meniscal repair model explants that were exposed to no strain, strain, no strain + IL-1, or strain + IL-1. The strains tested were 1% (top panel), 10% (middle panel), and 26% (bottom panel). The S-GAG release is expressed as µg S-GAG per mg wet weight + standard error. *: p ≤ 0.005 compared to all other treatments. +: p < 0.01 compared to no strain and strain.

Fig. 4

Nitric oxide (NO) release into the media of meniscal repair model explants that were exposed to no strain, strain, no strain + IL-1, or strain + IL-1. The strains tested were 1% (top panel), 10% (middle panel), and 26% (bottom panel). The NO release is expressed as µmol per g wet weight + standard error. *: p < 0.005 compared to all other treatments. +: p < 0.05 compared to no strain.

Fig. 5

Integrative shear strength of repair for meniscal repair model explants that were exposed to no strain, strain, no strain + IL-1, or strain + IL-1. The strains tested were 1% (top panel), 10% (middle panel), and 26% (bottom panel). The shear strength of repair is expressed as kPa + standard error. *: p < 0.05 compared to all other treatments. #: p < 0.005 compared to no strain and no strain + IL-1. +: p < 0.01 compared to 26% strain + IL-1.

Fig. 6

Histological images of paraffin embedded meniscal repair model explants stained with hematoxylin to identify the cell nuclei (black), fast green (green) to identify the collagen fibers, and safranin O (red) to stain proteoglycans. Samples were incubated with no IL-1 or 100 pg/mL IL-1 and subjected to 0%, 1%, 10%, or 26% strain. Scale bar is equal to 100µm.