McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Biomed Mater Res B Appl Biomater. 2010 Feb;92(2):390-6. doi: 10.1002/jbm.b.31527.
Sepsis is characterized by a systemic inflammatory response caused by infection, and can result in organ failure and death. Removal of inflammatory mediators such as cytokines from the circulating blood is a promising treatment for severe sepsis. We are developing an extracorporeal hemoadsorption device to remove cytokines from the blood using biocompatible, polymer sorbent beads. In this study, we used confocal laser scanning microscopy (CLSM) to directly examine adsorption dynamics of a cytokine (IL-6) within hemoadsorption beads. Fluorescently labeled IL-6 was incubated with sorbent particles, and CLSM was used to quantify spatial adsorption profiles of IL-6 within the sorbent matrix. IL-6 adsorption was limited to the outer 15 microm of the sorbent particle over a relevant clinical time period, and intraparticle adsorption dynamics was modeled using classical adsorption/diffusion mechanisms. A single model parameter, alpha = q(max) K/D, was estimated by fitting CLSM intensity profiles to our mathematical model, where q(max) and K are Langmuir adsorption isotherm parameters, and D is the effective diffusion coefficient of IL-6 within the sorbent matrix. Given the large diameter of our sorbent beads (450 microm), less than 20% of available sorbent surface area participates in cytokine adsorption. Development of smaller beads may accelerate cytokine adsorption by maximizing available surface area per bead mass.
脓毒症的特征是感染引起的全身炎症反应,可导致器官衰竭和死亡。从循环血液中去除细胞因子等炎症介质是治疗严重脓毒症的一种有前途的方法。我们正在开发一种体外血液吸附装置,使用生物相容性聚合物吸附珠从血液中去除细胞因子。在这项研究中,我们使用共焦激光扫描显微镜(CLSM)直接检查血液吸附珠内细胞因子(IL-6)的吸附动力学。用荧光标记的 IL-6 孵育吸附剂颗粒,并用 CLSM 定量 IL-6 在吸附剂基质中的空间吸附分布。在相关的临床时间段内,IL-6 的吸附仅限于吸附剂颗粒的外 15 微米,并且使用经典的吸附/扩散机制对颗粒内吸附动力学进行建模。通过将 CLSM 强度分布拟合到我们的数学模型来估计单个模型参数α=q(max)K/D,其中 q(max)和 K 是朗缪尔吸附等温线参数,D 是 IL-6 在吸附剂基质中的有效扩散系数。鉴于我们的吸附剂珠的大直径(450 微米),只有不到 20%的可用吸附剂表面积参与细胞因子的吸附。通过使每颗珠的可用表面积最大化,开发更小的珠可能会加速细胞因子的吸附。