Diffusion and convection in collagen gels: Implications for transport in the tumor interstitium
Diffusion and convection in collagen gels: Implications for transport in the tumor interstitium
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DOI：
10.1016/s0006-3495(02)73933-7
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发表时间：
2002-09-01
影响因子：
3.4
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Ramanujan, S;Pluen, A;Jain, RK
在0-4.5% w/v溶液中制备I型胶原凝胶，光漂白后荧光恢复测定示踪分子的扩散系数。当调整到考虑体内扭曲时，凝胶中的扩散系数与先前在四个具有相同胶原浓度的人类肿瘤异种移植物中的测量结果相匹配。相比之下，当制备的透明质酸溶液的浓度与这些肿瘤中报道的浓度相当时，其阻碍扩散的程度较小。通过静水压力下通过凝胶的流动来确定胶原蛋白的渗透性，并将其与应用Brinkman有效介质模型对扩散数据的预测结果进行了比较。渗透率预测在低浓度下与实验结果相符，但在高浓度下低估了测量值。凝胶中的渗透性测量结果与之前在肿瘤中的测量结果不匹配。通过透射电子显微镜和光学显微镜对凝胶进行可视化观察，发现低浓度下有长胶原纤维网络，高浓度下有短纤维网络。在胶原蛋白溶液中检测到可忽略不计的组装。然而，在凝胶前和凝胶后的样品中，扩散同样受到阻碍。在这些凝胶和肿瘤中的扩散和对流数据的比较表明，胶原蛋白可能比对流更能阻碍肿瘤中的扩散。这些发现对肿瘤药物传递和组织工程应用具有重要意义。
Diffusion coefficients of tracer molecules in collagen type I gels prepared from 0-4.5% w/v solutions were measured by fluorescence recovery after photobleaching. When adjusted to account for in vivo tortuosity, diffusion coefficients in gels matched previous measurements in four human tumor xenografts with equivalent collagen concentrations. In contrast, hyaluronan solutions hindered diffusion to a lesser extent when prepared at concentrations equivalent to those reported in these tumors. Collagen permeability, determined from flow through gels under hydrostatic pressure, was compared with predictions obtained from application of the Brinkman effective medium model to diffusion data. Permeability predictions matched experimental results at low concentrations, but underestimated measured values at high concentrations. Permeability measurements in gels did not match previous measurements in tumors. Visualization of gels by transmission electron microscopy and light microscopy revealed networks of long collagen fibers at lower concentrations along with shorter fibers at high concentrations. Negligible assembly was detected in collagen solutions pregelation. However, diffusion was similarly hindered in pre and postgelation samples. Comparison of diffusion and convection data in these gels and tumors suggests that collagen may obstruct diffusion more than convection in tumors. These findings have significant implications for drug delivery in tumors and for tissue engineering applications.