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

Abstract

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 [TNF ], matrix metalloproteinase [MMP]-9, macrophage migration inhibitory factor [MIF], MIP-1 , and MIP-2) 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, TNF , and MMP-9 were elevated in diabetic rats both 2 and 3 weeks postsurgery. The levels (both mRNA and protein) of MIF were increased at 2 weeks postsurgery and those of MIP-1 and MIP-2 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.

Addition of Resolvins D1 or E1 to Collagen Membranes Mitigates Their Resorption in Diabetic Rats

“…Increased lysis of various tissues in diabetics accompanies the exaggerated inflammation [14][15][16][17][18][19][20][63][64][65]. By inference, this is corroborated by our findings that addition of tetracycline (anti-collagenolytic) and hyaluronic acid (anti-inflammatory) to the membranes mitigated their excessive resorption in diabetic rats (our studies [43][44][45][46]).…”

“…Our previous studies [43][44][45][46] clearly indicate that CMs undergo a more rapid resorption when implanted under the scalp of hyperglycemic rats. This is associated with an increased presence of macrophages and other immune cells, and an increased production of pro-inflammatory cytokines such as IL-6 and TNFα.…”

“…Firstly, under diabetic conditions, there are increased levels of inflammation and thus secretion of pro-inflammatory mediators such as IL-1β, IL-6, and TNFα [3,5,8]. This is true for many organs, including the periodontium, for CMs implanted in diabetic animals (our studies [43][44][45][46]) and for other degradable devices implanted in diabetic animals [34][35][36]. Increased lysis of various tissues in diabetics accompanies the exaggerated inflammation [14][15][16][17][18][19][20][63][64][65].…”

“…The most commonly used membranes are resorbable, made of collagen (type 1 or 3), and their resorption is mediated by the collagenolytic activity of host cells [41,42]. Our previous studies have found that collagen membranes undergo an accelerated degradation in diabetic animals, accompanied by an inflammatory reaction [43][44][45][46].…”

Cross-Linked Hyaluronic Acid Slows Down Collagen Membrane Resorption in Diabetic Rats through Reducing the Number of Macrophages

“…Recently, several in vitro and in vivo animal studies have demonstrated some advantages using cross-linked HMW HA [34]. In a recent animal study, it was concluded that HMW HA does not interfere with tissue integration and structural degradation of Bio-Guide ® (Geistlich Pharma AG, Wolhusen, Switzerland) or OsseoGuard ® [35], two CMs which are frequently used for periodontal and bone regeneration.…”