Different pharmacological adjuncts have been investigated with the aim to arrest inflammatory response that potentiates the destruction of periodontal tissue thereby facilitating the repair of the damaged root surface by deposition of new cementum and formation of periodontal ligament. Antibiotics are a part of the pharmacological regime in such strategy. Sae Lim et al (1998) has shown that systemic tetracycline, with an anti- bacterial as well as anti-resorptive effects due to anti-collagenase activity, in a dog model resulted in more cemental healing compared to amoxicillin group. They also found that
tetracycline. Khin and Sae-Lim (2003) using a monkey model reported slightly higher occurrence of complete healing in delayed replanted teeth applied topically with minocycline, although the difference was not significant as compared to those without the treatment.
Bryson et al (2003) in a dog model reported no significant difference in remaining root mass or percentage of favorably healed root surfaces with and without minocycline treatment.
Therefore the use of topical minocycline for prevention of external resorption of the root does not provide predictable results. The use of steroids has been looked into with regards to reduction in inflammatory response by blocking macrophage action. Sae-Lim et al (1998) found that the topical addition of dexamethasone to storage media enhanced healing and reduced the incidence of replacement resorption. They accounted this finding to the reduction of damaging effects of inflammatory process by the glucocorticoids. Local administration of Ledermix, a mixture of democlocycline and triamcinalone has also being shown to reduce osteoclastic bone resorption. Wong and Sae-Lim (2002) studied the effect of immediate placement of intracanal Ledermix on root resorption of delayed –replanted teeth monkey teeth. They found that teeth with Ledermix placed had a higher occurrence of favorable healing compared to delayed-replanted teeth without Ledermix. Bryson et al (2002) also investigated on the effect of immediate placement of Ledermix in comparison with calcium hydroxide on teeth that were air dried for 1 hour. Tooth with ledermix showed less loss in root mass in comparison to those filled with calcium hydroxide.
7.2.1 Stimulation of cemental healing
In a replanted tooth, the ability to stimulate periodontal cell growth may limit the osteogenic cells ability to repopulate the denuded root surface, thus decreasing the occurrence of osseous replacement and increase the possibility of cemental healing. The use of an enamel matrix protein derivative such as Emdogain® has gained popularity in the regeneration of periodontal ligament in teeth with periodontal disease due its ability to
7, Treatment Objective of Periodontal Sequelae
increase expression of growth factors and promote primary cementum formation (Hammamoto et al 2002). Iqbal and Bamaas (2001) in dog model with 3 months observation found that teeth that were replanted with Emdogain® applied topically had a lower incidence of ankylosis compared to the group without Lam and Sae-Lim (2004). However studies have showen that Emdogain® did not appear to reduce significantly the occurrence of replacement resorption after 4 months of observation. This difference in the findings can be attributed to the difference in investigation model; the latter study investigated the effect of Emdogain® on regeneration of PDL in teeth that were air dried for 60 minutes. The use of growth factors in replanted teeth hinges on their ability to cause differentiation, mitogenesis and proliferation of periodontal ligament cells. Recent studies by Lafzi et al (2007) on the role of Emdogain in treating periodontal injury suggest that fibroblasts in the emdogain treated sites were more rounded with plump cytoplasms and euchromatic nuclei. A well- developed rough endoplasmic reticulum and numerous mitochondria could be detected. In contrast, the fibroblasts of non-Emdogain site were of flattened spindle-like morphology.
While the signs of apoptosis could rarely be detected at Emdogain site, apoptotic bodies and ultra-structural evidence of apoptosis (crescent-like heterochromatic nuclei and dilated nuclear envelopes) were consistent features at non-Emdogain site. The extracellular matrix at Emdogain site mainly consisted of well-organised collagen fibres, while non-Emdogain site contained sparse and incompletely-formed collagen fibres. Coccoid bacteria were noted within the extracellular matrix and neutrophils at non-Emdogain site. It seems that Emdogain may enhance certain features of gingival wound healing, which may be attributable to its anti-apoptotic, anti-bacterial or anti-inflammatory properties.
Sae-Lim et al (2004) found that topical application of basic fibroblast growth factor (bFGF) with fibrin glue showed insignificant higher occurrence of complete healing in
7.2.2 Slowing the resorption process
Current guidelines on treatment of avulsed teeth within 60 minutes or more of extra- oral dry period time by the American Association of Endodontists (AAE 2003) and International Association of Dental Traumatology (IADT 2001) suggest the removal of debris and necrotic periodontal ligament on the root surface by thorough curettage or use of acid.
Klinge et al (1984) studied the effect of citric acid on the repair of teeth after delayed replantation and found that after removing the non-vital soft tissue remnants, and demineralizing the root surface with citric acid for 4 minutes, the frequency of adverse healing was reduced. Bjorvatn et al (1989) recommended soaking the tooth for 5 minutes in 2.4% sodium fluoride solution acidulated to pH 5.5 prior to replantation and this has been shown to slow down osseous replacement and make the root resistant to resorption. Filling the socket with Emdogain has been advocated (AAE 2003, IADT 2001). Emdogain has been shown to stimulate periodontal cells from the socket. (Iqbal et al 2001). The use of HBSS supplemented with alendronate, a third generation biphosphonate, has been shown statistically significantly more healing, compared with those without alendronate, thus proving its inhibitory effect on osteoclasts that may slow down replacement resorption.
(Levin et al 2001)
8, Gene Profiling Principle of Microarray Using the Affymetrix Platform
8 GENE PR OFILING -PR INCIP LE OF M ICRO AR R AY US IN G TH E AF FYM E TR IX P L ATFOR M
Molecular heterogeneity of attachment apparatus/periodontium makes unraveling the mechanisms of periodontal regeneration a challenging task. The ensembles of genes that alter expression and thus are responsible for healing with complications following delayed replantation are largely unknown. The strategy of global gene expression profiling using Affymetrix GeneChip has been applied in an attempt to observe the molecular mechanisms of periodontal regeneration and healing following tooth replantation. The differentiated gene expression profiles may reveal characteristic patterns which may facilitate understanding of the healing response occurring in delayed replanted teeth. In this study we attempt to analyze mRNAs in PDL and alveolar bone from immediately and 60 minute-delayed replanted canine (dog) teeth. The identified genetic signature represented a description of the ensemble of bone and PDL related mRNAs, which are regulated by delayed replantation of teeth. This may provide a molecular insight into this clinical problem with potential bearing on future therapeutics.