Discussion.
The present data indicate that under optimal tissue conditions (in the absence of preoperative infection), apical root resection and placement of MTA creates an inflammation- free environment from the first postoperative week. Moderate-to-severe inflammation of the periradicular tissues was seen around one out of 14 MTA root-end fillings, and in three out of eight IRM-filled root ends. MTA proved to be a more favorable material in studies where MTA or amalgam was placed as retrograde filling material in infected dog teeth, 2-18 weeks postoperatively (Torabinejad et al.1995) and healthy monkey teeth, 5 months postoperatively (Torabinejad et al.1997).
The present data, indicating that MTA represents a biocompatible substrate to which formative cells can attach and produce new soft or hard tissue, are in agreement with previous data (Torabinejad et al. 1995). This study also supports previous findings that cells cultivated in vitro (Koh et al. 1998, Mitchell et al. 1999, Zhu et al. 2000), or mechanically exposed pulp cells in vivo (Tziafas et al. 2002), can be grown in intimate contact with this cement. Furthermore, these short-term observations show that early tissue healing events to MTA root-end filling material are characterized initially by fibrous connective tissue formation and secondarily by hard tissue repair.
The stimulatory effect of MTA on the biosynthetic activity of periradicular cells results primarily in stimulation of fibroblasts to lay down a fibrous connective tissue and rapid growth of periodontal ligament due to its high healing capacity. Hard tissue formation seems to be activated progressively from the peripheral root walls to the centre of the MTA. Two mechanisms could be suggested for the process leading to hard tissue formation over the MTA: either the fibrous connective tissue is calcified as the postsurgical time interval is increased or cells undergoing differentiation into hard tissue forming cells are progressively migrating between MTA surface and fibrous connective tissue, activating mineralization from the periphery of the root walls to the centre of the MTA filling. Since the nature of the hard tissue has not been specifically characterized, the mechanism for stimulating hard tissue formation over the MTA retrograde filling remains unknown. Nevertheless, it is reasonable to suggest that if activation of cementogenesis occurs after MTA placement at the apex, mineralization of previously formed connective tissue might be excluded as the main mechanism of hard tissue formation.
Based on the results of the present investigation, MTA is a biocompatible material when used in root-end cavities, stimulating repair of periradicular tissues. The nature of formative cells and newly formed hard tissue, as well as the mechanism controlling MTA-activated hard tissue formation, needs to be investigated further.

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