On the biological behavior of barrier membranes: implications for Guided Bone Regeneration. Clinical and Experimental studies

Sammanfattning: There is a continuous development of bone augmentation solutions to meet the rising demand for effective dental implant rehabilitations. One of the most used techniques is Guided Bone Regeneration (GBR). Although successful in the clinic, there is still scarce knowledge of the biological mechanisms behind bone regeneration, which therefore, turns out to be the appropriate aim of this project. The clinical Study I was a retrospective investigation on the long-term outcome of single implant treatment in the anterior maxilla, in conjunction with or immediately after Guided Bone Regeneration (GBR). The study on 74 included patients indicated the presence of factors negatively influencing marginal bone level, such as small defects, simultaneous GBR-implant placement, short healing time and onset of early and late complications. In Studies II and IV, resorbable and nonresorbable barrier membranes with different topographical features, were used to protect bone defects created in the rat femur and were compared with untreated sham defects. After different time points, samples were collected and processed for qPCR, histology, histomorphometry, electron microscopy, Western blot, and immunohistochemistry. In both studies, the protective role of the membranes as “physical barriers” was confirmed by the absence of soft tissue ingrowth inside the defects. Additionally, the membranes held an active role in wound healing dynamics. In Study II, the extracellular matrix-derived collagen membrane showed direct bone regenerative effects on the strength of attracting cells that release signals linked to bone formation and bone remodeling (BMP-2, FGF-2, TGF-β, ALP, CatK). In Study IV, the effect of two types of PTFE membranes in promoting favorable healing in the underlying bone defects was verified. The qPCR findings demonstrated comparable bone formation for the two barriers applied, and a superior “bioactive role” of the dual e-PTFE in the soft tissue compartment as revealed by high expression of tissue regeneration (FGF-2, FOXO1, COLL1A1) and vascularization (VEGF) genes as well as a downregulation of pro-inflammatory cytokines (IL-6 and TNF-). Finally, Study III was conducted to develop a methodological clinical platform to advance our scientific knowledge of the early bacterial colonization of barrier membranes. By employing CLSM imaging, it was shown that a dual expanded configuration of PTFE membrane resulted in less biofilm accumulation compared to solid dense PTFE. In conclusion, the present thesis provides a first line of information on molecular and cellular pathways, as well as microbiological response, triggered during GBR by different membranes, featuring a plausible active role in would healing dynamics along with the traditional barrier effect. Keywords: Guided bone regeneration, Resorbable membrane, Nonresorbable membrane, Gene expression, Histomorphometry, Soft tissue regeneration, Biofilm.