Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave ND20, Cleveland, OH, 44195, USA,
Med Biol Eng Comput. 2014 Apr;52(4):321-30. doi: 10.1007/s11517-013-1133-7. Epub 2013 Dec 27.
We have developed a mathematical model that allows simulation of oxygen distribution in a bone defect as a tool to explore the likely effects of local changes in cell concentration, defect size or geometry, local oxygen delivery with oxygen-generating biomaterials (OGBs), and changes in the rate of oxygen consumption by cells within a defect. Experimental data for the oxygen release rate from an OGB and the oxygen consumption rate of a transplanted cell population are incorporated into the model. With these data, model simulations allow prediction of spatiotemporal oxygen concentration within a given defect and the sensitivity of oxygen tension to changes in critical variables. This information may help to minimize the number of experiments in animal models that determine the optimal combinations of cells, scaffolds, and OGBs in the design of current and future bone regeneration strategies. Bone marrow-derived nucleated cell data suggest that oxygen consumption is dependent on oxygen concentration. OGB oxygen release is shown to be a time-dependent function that must be measured for accurate simulation. Simulations quantify the dependency of oxygen gradients in an avascular defect on cell concentration, cell oxygen consumption rate, OGB oxygen generation rate, and OGB geometry.
我们开发了一种数学模型，可以模拟骨缺损中的氧气分布，以此来探索细胞浓度、缺损大小和形状、局部供氧（利用产氧生物材料）以及细胞耗氧量等局部变化的可能影响。模型中纳入了产氧生物材料的氧气释放率和移植细胞群的耗氧率的实验数据。有了这些数据，模型模拟可以预测给定缺损内的时空氧浓度以及氧张力对关键变量变化的敏感性。这些信息可能有助于减少动物模型实验的数量，动物模型实验在确定当前和未来骨再生策略中细胞、支架和产氧生物材料的最佳组合方面非常重要。骨髓来源有核细胞的数据表明，氧消耗取决于氧浓度。产氧生物材料的氧气释放被证明是一个依赖时间的函数，必须进行测量才能进行准确的模拟。模拟量化了无血管缺损中氧梯度对细胞浓度、细胞耗氧率、产氧生物材料的氧气生成率和产氧生物材料几何形状的依赖性。
