Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogs

Hdl Handle:
http://hdl.handle.net/10675.2/346249
Title:
Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogs
Authors:
Hussein, Khaled A. ( 0000-0003-0824-511X )
Abstract:
Very often, delayed reconstruction becomes the setting of choice in the reconstruction of large segmental defects in the mandible. Our hypothesis is that rhBMP2 delivery would elicit endogenous expression of BMP2 and VEGF in the soft tissue bed of the defect. Such response is expected to be more pronounced in the immediate than the delayed reconstruction, which will correlate with the quantity and quality of bone formation in the two settings. We also hypothesized that vascular endothelial cells (ECs) of the surrounding soft tissue contribute to the endogenous production of BMP2. In this study we used a mandibular canine segmental defect model (35 mm), periosteum was excised and also the delayed reconstruction group was included in this study in addition to the control group. We investigated the effect of different reconstruction settings on the quantity and quality of bony regenerates; on the production of endogenous BMP2 from the soft tissue bed of the defects and finally we tried to explore the source of this rhBMP2- induced endogenous BMP2 production both in vivo and in vitro. This study demonstrated that rhBMP2 delivery is more effective in immediate reconstruction of large mandibular segmental defects. Immediate delivery of rhBMP2 yielded more adequate reconstruction of the defect after 12 weeks, evident by the quantity and quality of the bone regenerate. Only in the immediate reconstruction group, the advantageous bone parameters were associated with significant up-regulation of BMP2 mRNA and protein in the soft tissue bed of the defect. This suggests that endogenous-BMP2 is important in maintaining the short-acting effect of the delivered rhBMP2. Regarding the source of the endogenous-BMP2, protein co-localization with ECs marker suggested that these cells could be the source for the endogenous BMP2 secretion in response to rhBMP2 treatment. This was confirmed by the in-vitro results on both the mRNA and protein levels. The gradual increase in expression of BMP2 mRNA and the significant upregulation of secreted BMP2 protein upon stimulation of human umbilical vein endothelial cells with 100-ng/ml rhBMP2 recognized a new mechanism of positive feed back response of ECs in response to BMP2 treatment.
Affiliation:
Department of Oral Biology
Issue Date:
Dec-2012
URI:
http://hdl.handle.net/10675.2/346249
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/1268510351?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorHussein, Khaled A.en
dc.date.accessioned2015-03-06T19:42:41Zen
dc.date.available2015-03-06T19:42:41Zen
dc.date.issued2012-12en
dc.identifier.urihttp://hdl.handle.net/10675.2/346249en
dc.description.abstractVery often, delayed reconstruction becomes the setting of choice in the reconstruction of large segmental defects in the mandible. Our hypothesis is that rhBMP2 delivery would elicit endogenous expression of BMP2 and VEGF in the soft tissue bed of the defect. Such response is expected to be more pronounced in the immediate than the delayed reconstruction, which will correlate with the quantity and quality of bone formation in the two settings. We also hypothesized that vascular endothelial cells (ECs) of the surrounding soft tissue contribute to the endogenous production of BMP2. In this study we used a mandibular canine segmental defect model (35 mm), periosteum was excised and also the delayed reconstruction group was included in this study in addition to the control group. We investigated the effect of different reconstruction settings on the quantity and quality of bony regenerates; on the production of endogenous BMP2 from the soft tissue bed of the defects and finally we tried to explore the source of this rhBMP2- induced endogenous BMP2 production both in vivo and in vitro. This study demonstrated that rhBMP2 delivery is more effective in immediate reconstruction of large mandibular segmental defects. Immediate delivery of rhBMP2 yielded more adequate reconstruction of the defect after 12 weeks, evident by the quantity and quality of the bone regenerate. Only in the immediate reconstruction group, the advantageous bone parameters were associated with significant up-regulation of BMP2 mRNA and protein in the soft tissue bed of the defect. This suggests that endogenous-BMP2 is important in maintaining the short-acting effect of the delivered rhBMP2. Regarding the source of the endogenous-BMP2, protein co-localization with ECs marker suggested that these cells could be the source for the endogenous BMP2 secretion in response to rhBMP2 treatment. This was confirmed by the in-vitro results on both the mRNA and protein levels. The gradual increase in expression of BMP2 mRNA and the significant upregulation of secreted BMP2 protein upon stimulation of human umbilical vein endothelial cells with 100-ng/ml rhBMP2 recognized a new mechanism of positive feed back response of ECs in response to BMP2 treatment.en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/1268510351?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectrhBMP-2en
dc.subjectBMP2en
dc.subjectVEGFen
dc.subjectVascular Endothelial Cellsen
dc.subjectBoneen
dc.subjectReconstructionen
dc.titlePrimary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogsen
dc.typeDissertationen
dc.contributor.departmentDepartment of Oral Biologyen
dc.description.advisorElsalanty, Mohammeden
dc.description.committeeHamrick, M.; Stevens, M.; Al-Sabrawey, M.en
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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