Secondary bone grafting in alveolar clefts thesis

Adjunct orthodontic treatment was an essential requisite for inclusion. Pre-surgical maxillary occlusal radiograph taken within 1 month and post-operative occlusal radiograph taken at least 6 months after surgery were used for analysis. Unlike the routine occlusal X-rays, these radiographs were taken in such a way that central ray passes perpendicular to the cleft. Measurements included depth of the cleft and bone support for teeth mesial and distal to cleft.

Secondary Bone Grafting of Alveolar Clefts | SpringerLink

Measurements of the bony architecture used in this study were previously described by Aurouze et al. Eleven reference points were digitized on each radiograph. Microsoft Paint application was used to mark the reference points. Two examiners who were dental surgeons independently marked the points and they were blinded to the treatment phase of the patient and other clinical details.

Daskalogiannakis J, Ross RB Effect of alveolar bone grafting in the mixed dentition on maxillary growth in complete unilateral cleft lip and palate patients. De Angelis V Clinical management of the congenitally missing maxillary lateral incisor and mandibular second premolar: a clinical perspective.

Dempf R, Teltzrow T, Kramer FJ et al Alveolar bone grafting in patients with complete clefts: a comparative study between secondary and tertiary bone grafting. Denny AD, Talisman R, Bonawitz SC Secondary alveolar bone grafting using milled cranial bone graft: a retrospective study of a consecutive series of patients.

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Lilja J, Kalaaji A, Friede H et al Combined bone grafting and delayed closure of the hard palate in patients with unilateral cleft lip and palate: facilitation of lateral incisor eruption and evaluation of indicators for timing of the procedure. Newlands LC Secondary alveolar bone grafting in cleft lip and palate patients. Ozawa T, Omura S, Fukuyama E et al Factors influencing secondary alveolar bone grafting in cleft lip and palate patients: prospective analysis using CT image analyzer.

Precious DS A new reliable method for alveolar bone grafting at about 6 years of age. Robertsson S, Mohlin B The congenitally missing upper lateral incisor. Rune B, Jacobsson S Dental replacement resorption after bone grafting to the alveolar cleft. Semb G Effect of alveolar bone grafting on maxillary growth in unilateral cleft lip and palate patients.

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Shashua D, Omnell ML Radiographic determination of the position of the maxillary lateral incisor in the cleft alveolus and parameters for assessing its habilitation prospects. No significant difference was found between the non-inflammation and inflammation groups in terms of gender, age, or cleft type. Considering the microbial taxa in the salivary samples, 9 phyla, 14 classes, 24 orders, 45 families, and 71 genera with a relative abundance higher than 0. The most abundant phyla were Firmicutes an average of These five predominant phyla constituted The comparison of the relative abundance of bacterial taxa between the two groups both before and after the operation were shown in the S2 Fig for details, see the supplemental results in S1 File.


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The microbial diversity of the oral cavity differed significantly between the non-inflammation and inflammation groups after the operation S3 Fig. The variation in the overall bacterial community composition, based on unweighted UniFrac distance measurements, was compared between the non-inflammation and inflammation groups. Principal coordinate analysis PCoA plots based on the unweighted UniFrac metric revealed clustering of most inflammation samples, which were separated from the non-inflammation samples before and after the operation, indicating a difference in the salivary microbial communities of the two groups Fig 1B and 1C.

A The inflammation samples were significantly more similar to one another than the non-inflammation samples both in the pre- and post-operative comparison. Principal coordinate analysis PCoA plot shows clustering of most inflammation samples, which were separated from non-inflammation samples B before and C after the operation. Red and green dots indicate inflammation and non-inflammation samples, respectively. We compared relative abundance of OTUs between the inflammation and non-inflammation groups before the operation to investigate whether inflammation status was associated with the oral bacterial composition of individuals before the operation.

Analysis of the relative abundances of pre-operative bacteria showed 77 significantly different OTUs. There were 26 different OTUs with a relative abundance higher than 0. OTU, corresponding to Porphyromonas sp. In total, 26 OTUs with relative abundances higher than 0. The upper part of the diagram shows that the levels of 13 pre-operative OTUs were higher in the inflammation group, and the lower part shows that another 13 OTUs were lower. A higher proportion of OTU, corresponding to Porphyromonas sp. Based on information about different pre-operative OTUs relative abundance higher than 0.

The inflammation-related OTUs included Tannerella sp. These OTUs likely played a deciding role in dividing the groups. The OTUs corresponding to Streptococcus sp.


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  • Based on 26 different OTUs of the pre-operation relative abundance higher than 0. The 14 OTUs with the pink shadow on the right of the diagram were closely related to post-operative inflammation at the grafted sites. To better understand the association of the pre-operative bacteria that differed between inflammation and non-inflammation groups, we computed the correlation between the relative abundances of pre-operative OTUs in all samples. Co-occurrence networks were constructed based on the relative abundance profiles of pre-operative OTUs differing between the inflammation and non-inflammation groups.

    The sizes of the nodes are proportional to the average relative abundances of the OTUs. A cross-validated random forest model was created based on the 26 pre-operative OTUs with a relative abundance higher than 0. This classified model with three-fold cross-validation and five random trees was able to fit the post-operative status of grafted sites and yielded good classification results S2 Table and S1 File.

    Secondary repair of alveolar cleft with bone graft from iliac crest.

    The cross-validated error from the random forest model was 0. Additionally, the sensitivity and specificity of this classified model were This indicated that the 26 pre-operative OTUs could, to some extent, serve as microbial indicators for prognosis of the alveolar bone grafting. Post-operative surgical wound inflammation or infection is an important factor influencing the outcome of alveolar bone grafting and leads to a greater incidence of absorption of the graft [ 8 , 10 ].

    In previous reports, about one-third of patients with failed grafts had local infection or wound dehiscence [ 9 , 10 ]. Post-operative wound inflammation or infection is caused by many reasons.

    Secondary Bone Grafting of Alveolar Clefts

    As an intraoral surgery, alveolar bone grafting is considered a clean-contaminated surgical procedure because of the facultative pathogenic mixed flora of the oral cavity [ 11 ]. Moreover, poor oral hygiene is one of the reasons for surgical wound infections [ 9 ]. Pre-operative gingival health has been considered a major factor determining surgical success [ 30 ]. This study attempted to investigate oral microbiome profiles in children with the alveolar bone grafting and identify microbial indicators for prognosis evaluation. Based on the beta diversity of the OTU level between the non-inflammation and inflammation samples, microbial variation in the oral cavity differed significantly between the two groups both before and after the operation.

    The oral bacteria structure in the inflammation samples was significantly more similar than the non-inflammation samples. However, there was no significant difference between the two groups with regard to alpha diversity of oral microbiota before the operation. We suggest that the variation of bacterial OTU profiles in the pre-operative saliva may contribute to the post-operative inflammation of grafted sites.

    We further compared the oral microbial composition of the non-inflammation group with inflammation group both before and after the operation. Twenty-six pre-operative OTUs with a relative abundance higher than 0. Only the OTU corresponding to Porphyromonas sp. Our data suggests that the same surgery by same surgeon has different effects on the oral microbial composition from different individuals.

    When the oral microbial compositions before the operation differ between the inflammation and non-inflammation samples, the alveolar bone grafting could discriminatively influence the salivary microbial community from the different groups, which respectively shift to another ones. Thus, we emphasized the analysis of the pre-operative microbiota in the oral cavity of the children with CLP. Our analysis revealed that the inflammation-related OTUs included Tannerella sp. These enriched microbial species are most likely residents of normal oral flora, many of which are potential opportunistic pathogens, and could contribute to the post-operation inflammation and infection.

    Prevotella species are part of the human oral microbiota and play a role in the pathogenesis of periodontal disease and some extraoral infections, such as nasopharyngeal and odontogenic infections [ 31 , 32 ].

    Secondary Bone Grafting of Alveolar Clefts

    Prevotella intermedia is a Gram-negative, obligate anaerobic pathogenic bacterium, which is often found in acute necrotizing ulcerative gingivitis. It is commonly isolated from dentoalveolar abscesses, where obligate anaerobes predominate [ 33 ]. Prevotella nigrescens is part of the normal oral flora and leads to oral disease when the local tissue is infected. When Prevotella nigrescens colonize, they trigger an over-aggressive response from the immune system and increase the incidence of many diseases and infections [ 32 ].

    Gemella and Moraxella functioning as opportunistic pathogens, are primarily found in the mucous membranes, particularly in the oral cavity, where they are capable of causing severe localized or generalized infection in previously damaged tissue [ 34 ]. In the previous studies about human microbial ecosystems, several lines of evidence have demonstrated that the role of indigenous bacteria in controlling pathogenic colonization involves preventing pathogen expansion rather than retarding exogenous acquisition [ 35 — 37 ].

    It is also widely believed that environmental perturbations shift the balance of the oral microbiota and eventually lead to a predominance of pathogenic bacteria [ 29 ]. Thus, we suggest that a balanced oral microbiome is crucial in inhibiting the expanding of opportunistic pathogens and maintaining the stability of the microbial community, while destabilized microbial environment could potentially result in over-growth of these bacterial species and leads to increased risk of developing post-operative inflammation and infection.

    Furthermore, a cross-validated random forest model based on the pre-operative saliva OTUs was able to classify the post-operative status of grafted sites with high sensitivity and specificity Microbiota communities in the oral cavity are polymicrobial and exist principally as biofilms on the surfaces of the teeth, gums, mucosa, and tongue [ 38 ]. Because of metabolic inter-dependencies in the oral microbial ecosystem, many oral diseases are polymicrobial infections [ 39 , 40 ]. Although we recognize individual bacteria as potentially pathogenic factors that modulate or damage human cells in models of infection in vivo or in vitro, a more accurate perspective is one of a pathogenic community [ 41 ].

    Recent studies on the behavior of multispecies communities have shown that the presence of one or more bacteria can change virulence and gene expression in other pathogens [ 42 — 44 ]. Porphyromonas gingivalis , as one species of the genus Porphyromonas , is detected in low abundance in the oral cavity. However, it can cause a microbial shift in the oral cavity, allowing for uncontrolled growth of the commensal microbial community [ 45 ].

    It has been proved that Porphyromonas gingivalis is related to increasing the virulence of other commensal bacteria both in vivo and in vitro experiments. The outer membrane vesicles of Porphyromonas gingivalis have also been demonstrated to be necessary for Tannerella forsythia to invade epithelial cells [ 46 ].

    These studies indicate that the diseases associated with the human oral cavity may result from the activities of microbial communities and not only from certain individual microorganisms [ 41 ].