Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Exp Neurol. 2010 Jun;223(2):645-52. doi: 10.1016/j.expneurol.2010.02.014. Epub 2010 Mar 6.
Time-released delivery of soluble growth factors (GFs) in engineered hydrogel tissue constructs promotes the migration and proliferation of embedded cells, which is an important factor for designing scaffolds that ultimately aim for neural tissue regeneration. We report a tissue engineering technique to print murine neural stem cells (C17.2), collagen hydrogel, and GF (vascular endothelial growth factor: VEGF)-releasing fibrin gel to construct an artificial neural tissue. We examined the morphological changes of the printed C17.2 cells embedded in the collagen and its migration toward the fibrin gel. The cells showed high viability (92.89+/-2.32%) after printing, which was equivalent to that of manually-plated cells. C17.2 cells printed within 1mm from the border of VEGF-releasing fibrin gel showed GF-induced changes in their morphology. The cells printed in this range also migrated toward the fibrin gel, with the total migration distance of 102.4+/-76.1microm over 3days. The cells in the control samples (fibrin without the VEGF or VEGF printed directly in collagen) neither proliferated nor migrated. The results demonstrated that bio-printing of VEGF-containing fibrin gel supported sustained release of the GF in the collagen scaffold. The presented method can be gainfully used in the development of three-dimensional (3D) artificial tissue assays and neural tissue regeneration applications.
在工程化水凝胶组织构建体中缓释可溶生长因子（GFs）可促进嵌入细胞的迁移和增殖，这是设计旨在实现神经组织再生的支架的重要因素。我们报告了一种组织工程技术，可打印鼠神经干细胞（C17.2）、胶原蛋白水凝胶和释放生长因子（血管内皮生长因子：VEGF）的纤维蛋白凝胶，以构建人工神经组织。我们研究了打印的 C17.2 细胞在胶原蛋白中的形态变化及其向纤维蛋白凝胶的迁移。打印后，细胞的存活率高达 92.89+/-2.32%，与手动种植的细胞相当。打印在距 VEGF 释放纤维蛋白凝胶边界 1mm 范围内的 C17.2 细胞表现出 GF 诱导的形态变化。在此范围内打印的细胞也向纤维蛋白凝胶迁移，在 3 天内的总迁移距离为 102.4+/-76.1μm。对照样品（不含 VEGF 的纤维蛋白或直接在胶原蛋白中打印的 VEGF）中的细胞既没有增殖也没有迁移。结果表明，含有 VEGF 的纤维蛋白凝胶的生物打印支持 GF 在胶原蛋白支架中的持续释放。所提出的方法可有益地用于开发三维（3D）人工组织测定和神经组织再生应用。
