Efficacy of Biomimetic Collagen Membrane in Guided Tissue Regeneration: Animal Study

Background: Periodontitis is a kind of disease caused by the interaction of bacterial biofilm and host immune response, which usually leads to the breakdown of periodontal apparatus. How to regenerate the lost periodontal supporting tissue has been the primary goal of many researchers for several years. There have been many studies confirmed the use of guided tissue regeneration (GTR) in periodontal intrabony defects increases clinical attachment level, new bone formation and effectively reduces periodontal pocket. The key for guided tissue regeneration is to use a barrier membrane to exclude unwanted tissue type in the protected area. The evolution of barrier membrane from non-resorbable membranes in the past to resorbable membranes used today significantly reduced the need and pain of the second surgery after GTR. However, collagen membrane, the most used and biocompatible resorbable membrane, usually need chemical crosslinking for longer degradation time in vivo, that inevitably cause some extent of cytotoxicity. Recently, a new biomimetic membrane without chemical crosslinking has been proposed. This membrane made of decellularized extracellular matrix shows excellent biocompatibility and physical property. The primary object of this animal study was to test the efficacy of this biomimetic membrane in guided tissue regeneration. The second object is to compare that with a standard collagen membrane in the market. Materials and Methods: The third mandibular premolars and first molars of three mongrel dogs were extracted bilaterally, and the extraction sites were allowed to heal for 10 weeks. One-wall intrabony defects were prepared bilaterally on the mesial and distal side of the fourth mandibular premolars. Twelve intrabony defects were assigned to three treatment groups: test group (SIS + BioOssR); positive control (BioGideR + BioOssR); negative control (BioOssR only). Fluorescence bone labeling was administrated subcutaneously on the day of GTR surgery, four weeks and eight weeks post-operatively. The animals were sacrificed 12 weeks after surgery. For histometric analysis, defect height, junctional epithelium migration, new cementum, new bone height, and new bone area were measured. New bone volume was measured using microcomputed tomography. Fluorescence microscopic observation was done to figure out the possible sequence of new bone formation in each group. Result: No adverse effect was found in all three groups after GTR surgery. For new bone height, test group (4.80 ± 0.98mm) and positive control group (4.43 ± 1.29mm) showed superior results compared to negative control group (3.29 ± 0.83mm), but there is no statistical significance. New bone area (%) of the three groups was 23.77 ± 9.94% for the test group, 25.90 ± 12.22% for the positive control group, and 20.32 ± 8.59% for the negative control group. The differences between each group were not statistically significant. For new bone volume (%), analyzed from micro-CT, the result of the test group and the positive control group is very close (respectively 37.34 ± 9.56% and 38.07 ± 16.15%), higher than that of the negative control group (24.70 ± 7.97%), nevertheless, there is still no statistical significant. For fluorescence microscopy, the pattern of new bone formation usually begins from the border area of the defect toward the central part of the defect. However, the timing and the specific area of new bone formation are different in all three groups. It seems that the test group has a tendency of accelerating bone formation in the early phase of healing. Conclusion: The combination of the biomimetic membrane with bone grafting materials seems to have the potential to promote periodontal regeneration. However, due to limited sample size in this study, there is less possibility that the result between groups achieving statistic significance. More research is needed on the regeneration potential of this new biomimetic membrane. In addition, with the fluorescence bone labeling technique, not only the results of histology and micro-CT were supported, but also can we understand the mode of new bone formation in different groups.