BONE GROWTH AND RHBMP2

重组人骨形态发生蛋白-2 （rhBMP-2）正被评估为牙科和骨科适应症的骨生长诱导剂。在研究的给药系统中，剂量反应是模棱两可的，骨髓培养中持续应用rhBMP-2比短期暴露产生更强大的成骨细胞特征。该研究试图回答一个基本问题，即在缺陷部位持续释放rhBMP-2是否比立即释放更好地生长骨骼。兔颅骨缺损将作为骨生长的动物模型，大鼠颅骨缺损将作为体内释放模型。输送系统将由多孔聚乳酸-羟基乙酸酯（PLGA）微球生产，rhBMP-2已通过吸收和冻干结合。植入式基质通过将装载蛋白质的颗粒悬浮在2%羧甲基纤维素（CMC）中，冻干，并将干燥的材料切割成大小。通过选择PLGA和工艺参数来控制RhBMP-2的释放曲线，以获得尺寸和形貌相似的多孔颗粒。将进行RhBMP-2结合和释放，以选择两种聚合物类型，一种能够持续释放，另一种能够立即释放，用于生产和植入基质。在第一个动物实验中，将立即释放或缓释基质植入兔颅骨7.9 mm的圆形缺陷中。骨，根据炎症、新骨量、新骨类型、成纤维细胞水平、纤维化、脂肪、缺损边缘和血管状况评分，将在植入后6周进行评估。在第二个动物实验中，将含有放射性标记的rhBMP-2的基质植入大鼠颅骨，并在设定的时间取出进行分析。检验的假设将是：1)可以制备具有相似形貌的各种PLGA类型的多孔颗粒。2)可通过一种或混合的PLGA微球获得所需的释放曲线。3)在兔颅骨缺损中，连续4 - 6周给予同一剂量的rhBMP-2比在3 - 5天内给予相同剂量的rhBMP-2能产生更多的新骨。4) rhBMP-2在大鼠体内释放量与体外释放量呈正相关。组织修复，血管形成和神经生长的知识。此外，这项工作将进一步深入了解蛋白质以持续、受控的方式传递。

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is being evaluated as a bone growth inducer for dental and orthopedic indications. Dose responses have been equivocal in the delivery systems investigated and bone marrow cultures produced more robust osteoblastic characteristics from sustained application of rhBMP-2 than from short term exposure. The research proposed attempts to answer the fundamental question of whether a sustained released of rhBMP-2 within a defect site, grows bone better than immediate release. Rabbit calvarial defects will be the animal model for bone growth and rat calvarial defects will be the in vivo release model. Delivery systems will be produced from porous poly(lactide-co glycolide) (PLGA) microspheres to which rhBMP-2 has been incorporated by absorption and lyophilization implantable matrices are produced by suspending protein-loaded particles in 2% carboxymethyl cellulose (CMC), lyophilizing, and cutting the dried material to size. RhBMP-2 release profiles will be controlled by selection of PLGA and process parameters to obtain porous particles of similar size and morphology. RhBMP-2 binding and release will be performed to select two polymer-types, one capable of sustained release and another capable of immediate release, for production and implantable matrices. In the first animal experiment, immediate or sustained release matrices will be implanted into 7.9 mm circular defects in rabbit calvaria. Bone, scored by inflammation, new bone amount, new bone type, fibroblast levels, fibrosis, fat, defect edge, and vascularity will be evaluated six weeks post implantation. In the second animal experiment, matrices containing radiolabeled rhBMP-2 will be implanted in rat calvaria and removed at set times for analysis. The hypothesis tested will be: 1) Porous particles of various PLGA types can be prepared with similar morphology. 2) The desired release profile can be obtained from one thing or a blend of the PLGA microspheres. 3) In a rabbit calvarial defect, more new bone will result from delivering a dose of rhBMP-2, continuously, over a four to six week period, than from delivery of the same dose in three to five days. 4) In vivo release of rhBMP-2 determined in rats will correlate to in vitro release. Knowledge of how tissue repair, vascularization and nerve growth. Additionally, this work will provide further insight into the delivery of proteins in a sustained, controlled manner.