Biomedical Engineering Reference
In-Depth Information
4. Dentin scaffold for recombinant human BMP-2
4.1 Recombinant human BMP products
BMP-2, 4, and 7 are strong accelerating factors of bone induction. Currently, BMP-2 and
BMP-7 have been shown in clinical studies to be beneficial in the therapy of a variety of
bone-related conditions including delayed union and non-union. BMP-2 (Medtronic
Co.Ltd.) and BMP-7 (Stryker Biotech Co.Ltd.) have received Food and Drug Administration
(FDA) approval for human clinical uses (fractures of long bones, inter-vertebral disk
regeneration), by delivery in purified collagen matrix or ceramics. Moreover, the BMP-2
product has been approved for certain dental applications. BMP-7 has also found use in the
treatment of chronic kidney disease. In 2002, Curis licensed BMP-7 to Ortho Biotech
Products, a subsidiary of Johnson & Johnson.
4.2 Acceleration of bone induction by BMP2 in human DDM scaffold
The aim of the following study was to estimate the increase of the bone-inductive potency
by DDM combined with BMP-2 in rat subcutaneous tissues.
Composition of BMP-2 solution and DDM
One hundred micro-liter of recombinant human BMP-2 solution (0.0, 0.5, 1.0, 2.0, 5.0μg of
BMP-2) was mixed with 70 mg of human DDM in a sterilized syringe. The composite was
called as the BMP-2/DDM. The DDM alone with 100μl of PBS was also prepared as a BMP-
free control.
Bioassay in rats
Wistar rats (male, 4 week-old) were subjected to intraperitoneal anesthesia and incisions
were added to the back skin under the sterile conditions. Each animal received three BMP-
containing composites (BMP-2/DDM) and one BMP-free control (DDM alone). The
implanted materials were removed at 3 weeks after implantation, and prepared for
histomorphological examinations. All procedures were followed the Guidelines in Health
Sciences University of Hokkaido for Experiments on Animals.
Histological findings and Morphometric analysis at 3 weeks
In the BMP-2 (5.0μg)/DDM (70mg) group, bone with hematopoietic bone marrow
developed extensively at 3 weeks. Chondrocytes were found only in the BMP-2 (0.5,
1.0μg)/DDM groups (Table 1). The BMP-2 (2.0, 5.0μg)/DDM groups accelarated bone
induction predominantly (Fig. 7). In the DDM alone group, mesenchymal tissue was seen
between DDM particles, and hard tissue induction was not observed at 3 weeks (Fig. 8).
Morphometric analysis demonstrated that the volume of the induced bone and marrow
increased at BMP-2 dose-dependent manner, while the DDM decreased at the dose-
dependent (Table 1). Briefly, the volume of the bone and marrow in BMP-2 (1.0μg)/DDM
and BMP-2 (5.0μg)/DDM showed 3.7% and 26.3%, respectively. BMP-2 (0.5μg)/DDM
showed 0.0% and 4.0% in the volume of bone and cartilage, respectively.
Conclusion
BMP-2 strongly accelerated bone formation in the DDM carrier system. DDM never
inhibited BMP-2 activity and revealed better release profile of BMP-2. These results indicate
that human recycled DDM are unique, absorbable matrix with osteoinductivity and the
DDM should be an effective graft material as a carrier of BMP-2 delivering and a scaffold for
bone-forming cells for bone engineering.
