BONE GROWTH AND RHBMP2

重组人骨形态发生蛋白-2（rhBMP-2）作为一种骨生长诱导剂正在接受牙科和骨科适应症的评估。在研究的递送系统中，剂量反应不明确，持续应用rhBMP-2的骨髓培养物产生的成骨细胞特征比短期暴露更强。该研究试图回答一个基本问题，即在缺损部位持续释放rhBMP-2是否比立即释放更好地生长骨。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。递送系统将由多孔聚（丙交酯-共-乙交酯）（PLGA）微球生产，其中rhBMP-2已通过吸收和冻干掺入，可植入基质通过将载有蛋白质的颗粒悬浮在2%羧甲基纤维素（CMC）中、冻干并将干燥材料切割成一定尺寸来生产。将通过选择PLGA和工艺参数控制RhBMP-2释放曲线，以获得相似尺寸和形态的多孔颗粒。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，将速释或缓释基质植入兔颅骨中的7.9 mm圆形缺损中。将在植入后6周评价骨，通过炎症、新骨量、新骨类型、成纤维细胞水平、纤维化、脂肪、缺损边缘和血管分布进行评分。在第二项动物实验中，将含有放射性标记rhBMP-2的基质植入大鼠颅骨中，并在设定时间取出进行分析。检验的假设为：1）可以制备具有相似形态的各种PLGA类型的多孔颗粒。2)所需的释放曲线可以从PLGA微球的一种物质或共混物获得。3)在兔颅骨缺损中，在四至六周的时间内连续递送rhBMP-2剂量将比在三至五天内递送相同剂量产生更多的新骨。4)在大鼠中测定的rhBMP-2的体内释放将与体外释放相关。组织修复、血管化和神经生长的知识。此外，这项工作将进一步深入了解蛋白质以持续、受控的方式递送。

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.