Demineralized Dentin Matrix as a Carrier of Recombinant Human Bone Morphogenetic Proteins: <i>in Vivo</i> Study

Abstract

This study aimed to evaluate the effi cacy of rabbit demineralized dentin matrix (DDM) as a recombinant human bone morphogenetic protein-2 (rhBMP-2) carrier using the subcutaneous tissues of mice and rabbit calvarial critical-sized defects. DDM of rabbit, combined with rhBMP-2 (DDM/rhBMP-2) was transplanted into the subcutaneous tissues of 6 mice and 6 rabbit calvarial critical-sized defects (DDM = 0.03 g, control; DDM/rhBMP-2 = 0.03 g of DDM, 0.2 mg/ml, 5.0 μg of rhBMP-2, experimental). Both DDM and DDM/rhBMP-2 was transplanted into the left and right subcutaneous tissues of mice symmetrically. For rabbits, 4 round critical-sized defects (8 mm diameter) were formed on the exposed skull. DDM was transplanted into the 2 defects on the left sides (n = 12) and DDM/rhBMP-2 into the right sides (n = 12). Two animals among 6 mice and 6 rabbits were sacrifi ced respectively at the 1, 2, and 4 experimental weeks for the histological and histomorphometrical evaluations with hematoxylin and eosin staining. Tissues from rabbits were imaged via micro-computed tomography (μCT). DDM/rhBMP-2 in mice induced new bone formation at 2 weeks and maturation with bone marrow at 4 weeks. DDM/rhBMP-2 in rabbit calvarium induced new bone formation remarkably at 4 weeks 21.77-47.99% compared to the DDM. These observations suggest that DDM could be considered a potential carrier of rhBMP-2. The rhBMP-2 loaded on DDM enhanced bone formation.

Clinical application of autogenous demineralized dentin matrix loaded with recombinant human bone morphogenetic‐2 for socket preservation: A case series

“…However, the amount of bone formation 3‐6 months after the graft is noteworthy (34.39% in the DDM/rhBMP‐2 group and 29.75% in the DDM group) considering that the concentration of rhBMP‐2 used in this study was 0.2 mg/mL, which is approximately seven times lower than the presently approved concentration. The amount of bone formation 4 weeks after grafting in a rabbit calvarial defect model was reported to be greater in a group that was treated with DDM/rhBMP‐2 0.2 mg/mL than in a group that was treated with DDM alone (47.99% vs 24.94%) …”

“…The amount of bone formation 4 weeks after grafting in a rabbit calvarial defect model was reported to be greater in a group that was treated with DDM/rhBMP-2 0.2 mg/mL than in a group that was treated with DDM alone (47.99% vs 24.94%). 17 Along with the superior effects of BMP-2/ACS in preclinical models, clinical studies have demonstrated successful results There was less residual dentin after treatment with DDM/rhBMP-2 than after treatment with DDM alone; however, the difference was not statistically significant. Experimental studies of human dentin grafts in a rabbit model showed that the remodeling resorption process involves continuous resorption of dentin with bone replacement in the dentin resorption cavities after 6 months.…”

“…On the basis of the osteoinductive activity of DDM and its potential as a carrier for rhBMP‐2, as well as the reported synergistic effects of rhBMP‐2 and transforming growth factor beta in a variety of model systems, we hypothesized that the effect of DDM/rhBMP‐2 on socket preservation may be superior to that of DDM alone. Moreover, we expected synergistic effects between exogenous rhBMP‐2 and the endogenous growth factors in osteoinductive DDM that could allow the ideal concentration of exogenous rhBMP‐2 to be lowered …”

“…15 Furthermore, our previous reports have demonstrated that DDM has the highest released-to-loaded rhBMP-2 ratio, the slowest rate of release, and the highest induction of osteonectin expression, resulting in augmented formation of mature bone. 13 On the basis of the osteoinductive activity of DDM and its potential as a carrier for rhBMP-2, as well as the reported synergistic effects of rhBMP-2 and transforming growth factor beta in a variety of model systems, 13,[16][17][18] we hypothesized that the effect of DDM/rhBMP-2 on socket preservation may be superior to that of DDM alone. Moreover, we expected synergistic effects between exogenous rhBMP-2 and the endogenous growth factors in osteoinductive DDM that could allow the ideal concentration of exogenous rhBMP-2 to be lowered.…”

Histological Review of Demineralized Dentin Matrix as a Carrier of rhBMP-2

“…26 Three other studies used DDM dipped into the rhBMP-2 solution and freeze-dried as a single composite. [27][28][29] In clinical studies, 29-31 the rhBMP-2 concentration within DDM/rhBMP-2 was set at 0.2 mg/mL, which is lower than the FDAapproved concentration of 1.5 mg/mL 1 .…”