Ruhe P Quinten, Hedberg Elizabeth L, Padron Nestor Torio, Spauwen Paul H M, Jansen John A, Mikos Antonios G
J Bone Joint Surg Am. 2003;85-A Suppl 3:75-81. doi: 10.2106/00004623-200300003-00013.
In bone tissue engineering, poly(DL-lactic-co-glycolic acid) (PLGA) microparticles are frequently used as a delivery vehicle for bioactive molecules. Calcium phosphate cement is an injectable, osteoconductive, and degradable bone cement that sets in situ. The objective of this study was to create an injectable composite based on calcium phosphate cement embedded with PLGA microparticles for sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2).
(125) I-labeled rhBMP-2 was incorporated in PLGA microparticles. PLGA microparticle/calcium-phosphate cement composites were prepared in a ratio of 30:70 by weight. Material properties were evaluated by scanning electron microscopy, microcomputed tomography, and mechanical testing. Release kinetics of rhBMP-2 from PLGA/calcium-phosphate cement disks and PLGA microparticles alone were determined in vitro in two buffer solutions (pH 7.4 and pH 4.0) for up to twenty-eight days.
The entrapment yield of rhBMP-2 in PLGA microparticles was a mean (and standard deviation) of 79% +/- 8%. Analysis showed spherical PLGA microparticles (average size, 17.2 +/-1.3 micro m) distributed homogeneously throughout the nanoporous disks. The average compressive strength was significantly lower (p < 0.001) for PLGA and calcium-phosphate cement composite scaffolds than for calcium-phosphate cement scaffolds alone (6.4 +/- 0.6 MPa compared with 38.6 +/- 2.6 MPa, respectively). Average rhBMP-2 loading was 5.0 +/- 0.4 micro g per 75-mm (3) disk. Release of rhBMP-2 was limited for all formulations. At pH 7.4, 3.1% +/- 0.1% of the rhBMP-2 was released from the PLGA/calcium-phosphate cement disks and 18.0% +/- 1.9% was released from the PLGA microparticles alone after twenty-eight days. At pH 4.0, PLGA/calcium-phosphate cement disks revealed more release of rhBMP-2 than did PLGA microparticles alone (14.5% +/- 6.3% compared with 5.4% +/- 0.7%) by day 28.
These results indicate that preparation of a PLGA/calcium-phosphate cement composite for the delivery of rhBMP-2 is feasible and that the release of rhBMP-2 is dependent on the composite composition and nanostructure as well as the pH of the release medium.
在骨组织工程中，聚（DL-乳酸-乙醇酸共聚物）（PLGA）微粒常被用作生物活性分子的递送载体。磷酸钙骨水泥是一种可注射、具有骨传导性且可降解的骨水泥，能在原位固化。本研究的目的是制备一种基于嵌入PLGA微粒的磷酸钙骨水泥的可注射复合材料，用于重组人骨形态发生蛋白-2（rhBMP-2）的持续递送。
将（125）I标记的rhBMP-2掺入PLGA微粒中。以重量比30:70制备PLGA微粒/磷酸钙骨水泥复合材料。通过扫描电子显微镜、微型计算机断层扫描和力学测试评估材料性能。在两种缓冲溶液（pH 7.4和pH 4.0）中体外测定rhBMP-2从PLGA/磷酸钙骨水泥圆盘和单独的PLGA微粒中的释放动力学，长达28天。
rhBMP-2在PLGA微粒中的包封率平均（及标准差）为79%±8%。分析显示球形PLGA微粒（平均尺寸，17.2±1.3μm）均匀分布于整个纳米多孔圆盘中。PLGA和磷酸钙骨水泥复合支架的平均抗压强度显著低于单独的磷酸钙骨水泥支架（分别为6.4±0.6 MPa和38.6±2.6 MPa，p<0.001）。每75-mm（3）圆盘的平均rhBMP-2负载量为5.0±0.4μg。所有配方中rhBMP-2的释放均有限。在pH 7.4时，28天后，3.1%±0.1%的rhBMP-2从PLGA/磷酸钙骨水泥圆盘中释放，18.0%±1.9%从单独的PLGA微粒中释放。在pH 4.0时，到第28天，PLGA/磷酸钙骨水泥圆盘显示出比单独的PLGA微粒更多的rhBMP-2释放（分别为14.5%±6.3%和5.4%±0.7%）。
这些结果表明制备用于递送rhBMP-2的PLGA/磷酸钙骨水泥复合材料是可行的，并且rhBMP-2的释放取决于复合材料的组成和纳米结构以及释放介质的pH值。
