Systemic tetracycline delays degradation of three different collagen membranes in rat calvaria

Objectives: The aim of this study was to quantitatively evaluate the effect of systemic tetracycline (TTC) on the degradation of three different collagen membranes.

Materials and methods: Collagen membranes were cut into 5 mm diameter membrane discs and labeled with aminohexanoyl-biotin-N-hydroxy-succinimide ester. One membrane disc each of a non-cross-linked [BioGide^® (BG)], glutaraldehyde cross-linked [BioMend Extend^® (BM)], and ribose cross-linked [Ossix^™ (OS)] was implanted on the calvaria of 40 Wistar rats. Another 10 biotinylated collagen membrane discs from each membrane type were processed for histologic observation and served as baseline; half of them (five from each group) were also treated with formic acid to inspect possible interference with biotinilazation of collagen by formic acid used during the decalcification process. A 10 mg/kg dose of TTC (50% of the minimal recommended antibacterial dose) to the experimental (20 animals) and saline to the control (20 animals) group was administered intramuscularly every 3 days. From each group, block sections were retrieved in half of the animals after 14 days and in the remaining after 28 days. Decalcified tissue histology was stained with streptavidin horseradish peroxidase. A computer-assisted program measured the membranes' collagen contents. Statistical analysis consisted of analysis of variance (ANOVA) with repeated measures.

Results: No statistically significant differences in collagen contents were appreciated between biotinylated non-implanted membranes treated or not treated by formic acid. Systemic TTC had a different effect on the bio-degradation of the membranes: while it significantly decreased the resorption of two of the membranes (BG and BM), it had minimal influence on the ribose cross-linked membrane (OS). ANOVA with repeated measures, tests of within-subjects effects, showed a statistically significant difference between the membranes (P<0.001), within the membranes at the different time-points (P<0.001), a significant interaction between membranes and time and between the membranes and administered TTC (P<0.001). Test of between-subject effects revealed a statistically significant interaction with time and with TTC (P<0.001).

Conclusions: Systemically administered TTC in sub-antibacterial doses may offer a possible treatment alternative to reduce bio-degradation and enhance bio-durability of certain collagen membranes. The findings of the present study could have clinical application in large non-self-contained bone defects, where prolonged membrane barrier functions are desirable.