Reconstruction of Mandibular Continuity Defects Using Recombinant Human Bone Morphogenetic Protein 2: A Note of Caution in an Atmosphere of Exuberance

Legacy Emanuel Hospital and Health Center, Oregon Health & Science University, Portland, OR, USA.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons (Impact Factor: 1.43). 12/2009; 67(12):2673-8. DOI: 10.1016/j.joms.2009.07.085
Source: PubMed
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  • Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 12/2009; 67(12):2557-8. DOI:10.1016/j.joms.2009.10.019 · 1.43 Impact Factor
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    ABSTRACT: This article reviews literature pertaining to advances in oromandibular reconstruction in the context of a 30-year background of microvascular free tissue transfer, which still represents the current standard of care. Most literature reiterates established patterns of reconstruction. Notable exceptions address these key areas: the use of computer-assisted modeling to more closely and efficiently design the excision of the mandible, to produce the template and to contour the fibula bone to fit the defect; the evolution of plating techniques to maximize the bony repair; distraction osteogenesis; tissue engineering; and optimal techniques for dealing with osteonecrosis, from both radiation and bisphosphonate use. Osteocutaneous free flaps remain the standard of care. The fibula flap has emerged as the accepted favorite among these flaps. Evolution of fibula flap reconstruction constitutes a major portion of the current literature. Improvements upon free tissue transfer are currently elusive, largely due to associated radiation. Tissue engineering holds promise as the next plateau but is not yet readily applicable.
    Current opinion in otolaryngology & head and neck surgery 02/2011; 19(2):119-24. DOI:10.1097/MOO.0b013e328344a569 · 1.84 Impact Factor
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    ABSTRACT: The ability of recombinant human bone morphogenetic protein 2 on absorbable collagen sponge (rhBMP2/ACS) to regenerate bone in segmental defect has been well characterized. However, clinical results of rhBMP2/ACS constructs in secondary reconstruction of large mandibular and craniofacial defects have not been consistent. We hypothesized that rhBMP2 delivery triggers an endogenous response in the soft tissues surrounding the defect, in the form of expression of BMP2 and vascular endothelial growth factor (VEGF). Such osteogenic response will occur only after immediate, as opposed to delayed, rhBMP2 delivery, suggesting a new explanation to the difference in bone regeneration between the two settings. A 35-mm segmental bone and periosteum defect was created on one side of the mandible in 16 dogs divided in three groups. Group 1 (Gp1, n=6) ACS was loaded with 8 mL of rhBMP2 (0.2 mg/mL). In Gp2 (n=5) the same dose of rhBMP2/ACS was delivered into the defect 4 weeks after surgery. In Gp3 (control; n=5) the defect was reconstructed using ACS loaded with 8 mL of buffer only (devoid of rhBMP2). Tissues were collected after 12 weeks of reconstruction in all groups. Direct measurement of physical dimensions of regenerates and bone morphometry was performed to evaluate bone regeneration. The mRNA expression of both BMP2 and VEGF in the soft tissue surrounding the defect was evaluated using real-time quantitative PCR. Both BMP2 and VEGF proteins were quantified in immunostained sections. Immunoflurescence colocalization of BMP2 and acetylated low density lipoprotein (AcLDL) was done to detect the source of BMP2. Immediate delivery yielded better bone regeneration. Both BMP2 and VEGF mRNA expression was upregulated only in Gp1 (+7.3, p=0.001; +1.53, p=0.001, respectively). BMP2 protein was significantly higher in the immediate reconstruction group; however, VEGF protein was undetected in the examined sections. Immediate delivery of rhBMP2 seemed to induce endogenous release of BMP2 from the surrounding soft tissues, an effect that was lacking in delayed delivery and may explain the variability of clinical results associated with BMP2 use. Colocalization of BMP2 and endothelial cells (ECs) suggested that ECs could be the source of endogenous BMP2.
    Tissue Engineering Part A 03/2012; 18(5-6):665-75. DOI:10.1089/ten.TEA.2011.0148 · 4.64 Impact Factor
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