Restoration of occlusal function using osseointegrated implants in the canine mandible reconstructed by rhBMP‐2

Abstract

Bone morphogenetic proteins have been found to be one of the most promising osteoinductive substances and they are expected to be utilized clinically for the reconstruction of defective mandibles. However, newly formed bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) has not yet been proven able to withstand the masticatory force applied by oral implants. In this study, we examined the qualitative changes in an rhBMP-2-induced mandible from the functional force of osseointegrated oral implants. Segmental (30 mm) bone defects were created in the mandibles of beagles. A poly D,L-lactic coglycolic acid-coated gelatin sponge impregnated with rhBMP-2 was grafted to the resected canine mandible. The new bone was formed 8 weeks after surgery and the Brånemark system fixtures were implanted into the reconstructed mandible. After another 8 weeks, the prosthesis was placed over the oral implants. The prosthesis was maintained in occlusion with the opposing natural dentition for 0, 4, 12, 24, or 48 weeks before the animal was euthanized. The quality of regenerated bone was then evaluated histologically and the osseointegration ratio between oral implants and the bonemeasured. During the first 4 weeks, the ratio remarkably increased from 48.9% to 64.5%. After 48 weeks, the ratio approached about 74.5%. The bone loaded for 48 weeks had undergone extensive remodeling and consolidation; its quality was better and maturer than that of bone that was not loaded. These results indicated that the newly formed bone induced by rhBMP-2 was able to withstand the masticatory force applied by oral implants and had become as functionally mature as a natural bone.

Tissue-Engineered Mandibular Bone Reconstruction for Continuity Defects: A Systematic Approach to the Literature

“…In line with these results are the reported effects of rhBMP-2 15,31,32,98,99,103,110 and rhBMP-7 33 for mandibular bone regeneration in continuity defects. On the other hand, it should be mentioned that rhBMP-2, in the reports of Zhou et al 109 and Seto et al, 102 as well as rhBMP-7, in the paper of Ayoub et al, 17 have not always been associated with bony union.…”

“…31 102 and a bovine collagen type I carrier wrapped into a sterno-occipitalis muscle flap 17 were not associated with predictable defect bridging.…”

“…Furthermore, in total, 15 scientific papers 15,18,29,31,32,[97][98][99][101][102][103]105,106,109,110 reporting on recombinant human bone morphogenetic protein-2 (rhBMP-2) as well as five publications 16,17,19,30,33 presenting data on recombinant human bone morphogenetic protein-7 (rhBMP-7) were eventually included in the current systematic approach. Thereby, the brief summarized studies of Kontaxis et al, 16 Abu-Serriah et al, 19 Boyne, 29,101 Busuttil Naudi et al, 30 and Toriumi et al 97 may give a good general impression of the effectiveness of rhBMPs regarding the quantity as well as quality of induced bone for the reconstruction of continuity mandibular defects (Details can be found in Addendum No.…”

“…Furthermore, these scaffolds should possess (3) suitable surface chemistry for cell attachment, proliferation, and differentiation, and (4) mechanical properties to match those of the tissues at the site of implantation. 9 At present, a multitude of scaffolds made of various material [10][11][12][13][14][15][16][17][18][19] in combination with bioactive substances or osteogenic bone marrow stromal cells (BMSCs) 10,[20][21][22][23][24][25][26] to initiate or enhance bone formation [15][16][17]19,[27][28][29][30][31][32][33] are under study. In 2006, Ikada defined a concept on methodology in tissue engineering as (1) placing the construct scaffold in a bioreactor to reconstruct an engineered tissue in vitro called in vitro (or ex vivo) tissue engineering and (2) implantation of the construct scaffold in the body until a new tissue is regenerated in vivo called in vivo (or in situ) tissue engineering.…”

Application of Regenerative Medicine to Mandibular Reconstruction

“…However, the only growth factors approved by the Food and Drug Administration are BMP-2,7 for augmentation of the sinus floor (sinus lift) and PDGF/beta-tricalcium phosphate for periodontal tissue reproduction; no growth factors are currently approved for mandibular bone regeneration. Therefore, the following fundamental techniques are necessary to obtain sufficient bone regeneration by the present method: 1) dense closing of the wound in the mouth, 2) preservation of a sufficient quantity of PCBM by harvesting from the posterior iliac crest or both anterior iliac crests, 3) insertion of the blood vessel into the PCBM to ensure abundant blood circulation [13], 4) strict initial fixation immediately after the operation using intermandibular fixation or other methods, and 5) bone maturation by the masticatory load after bone regeneration [14,15].…”