Accelerated degradation of collagen membranes in type 1 diabetic rats is associated with increased expression and production of several inflammatory molecules

Background: Membrane durability is critical for regenerative procedures. We reported previously that type 1-like diabetes in rats accelerates the degradation of collagen membranes and we tested here whether this is associated with increased local production of inflammatory molecules as part of a diabetes-induced chronic inflammation around and within the membranes. Methods: Collagen membrane discs were implanted under the scalp in diabetic (streptozotocin-induced) and control rats, which were sacrificed after 2 or 3 weeks. Total RNA and proteins were isolated from the membrane and its surrounding tissues and the expression and production of six inflammatory molecules (interleukin-6 [IL-6], tumor necrosis factor alpha [TNFα], matrix metalloproteinase [MMP]-9, macrophage migration inhibitory factor [MIF], MIP-1α, and MIP-2α) was measured using real-time PCR and western blotting, respectively. Minimal histological analysis of the membranes was conducted to conform to previous studies. Results: Hyperglycemia resulted in reduced membrane thickness (by 10% to 25%) and increased mononuclear infiltrate inside the membrane. mRNA and protein levels of IL-6, TNFα, and MMP-9 were elevated in diabetic rats both 2 and 3 weeks post-surgery. The levels (both mRNA and protein) of MIF were increased at 2 weeks post-surgery and those of MIP-1α and MIP-2α at 3 weeks. There was a very good match in the temporal changes of all examined genes between the mRNA and protein levels. Conclusions: Elevated local production of inflammatory cytokines and MMPs, together with apparent mononuclear infiltrate and increased collagenolysis confirm that hyperglycemia leads to a chronic inflammation in and around the implanted collagen membranes, which reduces membrane longevity.