Department of Orthopedic Surgery, College of Medicine, Seoul National University, SMG-SNU Boramae Medical Center, 425 Shindaebang-2-Dong, Seoul 156-707, Korea.
J Mater Sci Mater Med. 2013 Sep;24(9):2117-27. doi: 10.1007/s10856-013-4967-5. Epub 2013 Jun 1.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) requires carriers for clinical effectiveness. In this study, whether porous beta-tricalcium phosphate (β-TCP)-based ceramics are ideal carriers for rhBMP-2 was investigated. Hydroxyapatite (HA), β-TCP, TCP/HA (80 %/20 %), HA with rhBMP-2, TCP with rhBMP-2, and TCP/HA (80 %/20 %) with rhBMP-2 were manufactured by a sponge method with a pore size of 300 μm or more and macro-porosity of 83 %. The alkaline phosphatase (ALP) activity and ALP expression of the cells with 100 % β-TCP granules were more increased than the those of cells with 100 % HA and TCP/HA (80 %/20 %) at the baseline or when treated with 15 ng/ml of rhBMP-2. In an SD rat calvarial defect model, new bone formation was evidently shown in the TCP 100 %-rhBMP-2 and TCP/HA (80 %/20 %)-rhBMP-2 groups, showing that the most affected area was filled with newly-formed bone, that the percent bone volume and trabecular number were larger when compared to the groups without rhBMP-2 treatment at both 4 and 8 weeks after surgery using micro-CT and histology. Porous TCP-based ceramic granules enhanced the osteoblastic differentiation in the hMSC system when treated with 15 ng/ml of rhBMP-2 and accelerated bone-healing by trabecular number in a rat calvarial defect model. Thus, in this study it was proposed that TCP-based ceramics might be useful carriers of rhBMP-2.
重组人骨形态发生蛋白-2(rhBMP-2)需要载体才能发挥临床效果。本研究旨在探讨多孔β-磷酸三钙(β-TCP)基陶瓷是否为 rhBMP-2 的理想载体。通过海绵法制备了孔径为 300μm 以上且具有 83%大孔率的羟基磷灰石(HA)、β-TCP、TCP/HA(80%/20%)、负载 rhBMP-2 的 HA、负载 rhBMP-2 的 TCP 以及负载 rhBMP-2 的 TCP/HA(80%/20%)。当用 15ng/ml 的 rhBMP-2 处理时,100%TCP 颗粒组的碱性磷酸酶(ALP)活性和 ALP 表达均高于 100%HA 和 TCP/HA(80%/20%)组的基线水平或处理组。在 SD 大鼠颅骨缺损模型中,TCP 100%-rhBMP-2 和 TCP/HA(80%/20%)-rhBMP-2 组中均可见明显的新骨形成,表明受影响最严重的区域被新形成的骨所填充,术后 4 周和 8 周时,与未用 rhBMP-2 治疗的组相比,骨体积百分比和小梁数均较大。在用 15ng/ml 的 rhBMP-2 处理时,多孔 TCP 基陶瓷颗粒增强了 hMSC 系统中成骨细胞的分化,并通过小梁数加速了大鼠颅骨缺损模型的骨愈合。因此,本研究提出 TCP 基陶瓷可能是 rhBMP-2 的有用载体。