Fogorvosi szemle, 2007 (100. évfolyam, 1-6. szám)

2007-10-01 / 5. szám

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FOGORVOSI SZEMLE ■ 100. évf. 5. sz. 2007.

ro effects of EMD on dermal fibroblasts and on microvascular endothelial cells. EMD treatment increased the amount of granulation tissue and accelerated time to complete epithelialization by 3 days compared to the vehicle treatment. In cultured fibroblasts, vascular endothelial growth factor levels in conditioned media were increased more than fivefold. EMD also increased release of matrix metalloproteinase-2 more than threefold from fibroblasts and from endothelial cells. It was concluded that EMD significantly accelerated wound closure in rabbits, possibly by increasing levels of growth factors and proteinases important for granulation tissue formation and granulation. It was shown that EMD may express some angiogenetic effects which might play an important role in early wound healing [50]. Recent results have pointed to the anti-inflammatory properties of EMD which attenuated the release of TNF-a and interleukin-8 in whole blood from healthy donors challenged by lipopolysaccharide or peptidoglycan [51]. Furthermore, it was shown that EMD inhibits the attachment of a typical breast cancer cell line (MCF-7) to a bone matrix, thus suggesting that EMD might be useful as an anti-adhesive agent for breast cancer cells to bone in vivo [52],

In conclusion the data from in vitro studies strongly indicate that EMD affects important wound healing mechanisms. However, at the current time, it appears that the underlying molecules and mechanisms are still not completely understood.

Controlled histological studies in animals

In an experimental study in rats the effects and distribution of EMD in the periodontal tissues of maxillary rat molars transplanted to a subcutaneous position in the abdominal wall was studied [53]. Molars were transplanted with or without EMD either immediately after extraction or after drying them for 30 min. After 2 days, 1,2 or 4 weeks the rats were killed and the teeth were examined by means of light microscopy and immunohistochemistry with anti-amelogenin antibodies. The results revealed that teeth transplanted immediately after extraction showed formation of alveolar bone separated from the dental roots by a periodontal space, regardless of the use of EMD. Among the teeth that were transplanted with EMD after drying for 30 min, new alveolar bone was formed in five out of eight teeth after 2 and 4 weeks. None of the teeth that were dried for 30 min. and transplanted without EMD showed alveolar bone formation. Only one tooth transplanted with EMD showed root resorption after drying, while resorption was noted in all teeth transplanted without EMD. EMD was detected already after 2 days on all teeth transplanted with EMD and was still demonstrable after 4 weeks. Results from an experiment in dogs have shown that the application of EMD in intrabony

defects may significantly stimulate proliferation of periodontal ligament cells [54], However, this effect was limited to the first 4 weeks following surgery, thus indicating that the main effect of EMD is limited to the early stage of periodontal wound healing. In an experimental study in rat periodontal window wounds in which there is no microbial biofilm or epithelial downgrowth defects were filled with either vehicle (control) or EMD (test) [55]. The animals were sacrificed at 7, 14 and 21 days after wounding. Specimens of periodontium were immunostained for osteopontin, bone sialoprotein, osteocalcin as markers of osteogenic differentiation and for a-smooth muscle actin, a myofibroblastic marker. The results have indicated that EMD did not apparently affect the expression of differentiation markers or bone matrix protein synthesis in the repopulation response of wounded rat molar periodontium. It was suggested that the effect of EMD on wound healing in the periodontium may be independent of differentiation in the cell populations examined in the type of model used [55].

In a controlled histological study, recession defects were created and treated with EMD [56]. Standardized defects were created, by surgically removing the entire buccal bone plate and the root cementum. The test defects were treated with EMD, while in the control defects a coronally repositioned flap was made. Eight weeks after surgery the animals were sacrificed and the appropriate jaw segments histologically evaluated. The results have shown that in all test defects a new periodontium, i.e. acellular cementum with inserting collagen fibers and new alveolar bone developed. In the control defects, the healing was characterized by a long junctional epithelium with very limited cementum and new bone formation. If in the control defects new cementum was formed, it was mostly cellular and only partly attached at the root surface. An interesting aspect of this study is that in the test defects no root resorption occurred, while in the control defects the root resorption was a very frequently found phenomenon. It is important to mention that during the entire study period no oral hygiene measures were carried out. In an experimental study in monkeys acute fenestration-type defects were surgically created and subsequently treated with a) Guided Tissue Regeneration (GTR), b) EMD, or c) coronally repositioned flaps (control) [57], The results have shown that all 3 treatment approaches enhanced formation of new connective tissue attachment and new bone without major differences between the groups. However, the results also indicated that acute fenestration-type defects do not seem to be the ideal model for testing the potential of any type of regenerative approach [57]. In two subsequent studies in monkeys, recession-type and intrabony defects were created surgically and then exposed to dental plaque infection [58, 59]. Following initial periodontal therapy consisting of oral hygiene measures and topical application of chlorhexidine the