Baptista Pedro M, Orlando Giuseppe, Mirmalek-Sani Sayed-Hadi, Siddiqui Mohummad, Atala Anthony, Soker Shay
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:6526-9. doi: 10.1109/IEMBS.2009.5333145.
The use of synthetic and naturally-derived scaffolds for bioengineering of solid organs has been limited due to a lack of an integrated vascular network. Here, we describe fabrication of a bioscaffold system with intact vascular tree. Animal-donor organs and tissues, ranging in size up-to thirty centimeters, were perfused with decellularization solution to selectively remove the cellular component of the tissue and leave an intact extracellular matrix and vascular network. The vascular tree demonstrated sequential fluid flow through a central inlet vessel that branched into an extensive capillary bed and coalesced back into a single outlet vessel. In one example, the liver, we used central inlet vessels to perfuse human and animal liver cells through the bioscaffold to create a functional liver tissue construct in vitro. These results demonstrate a novel yet simple and scalable method to obtain whole organ vascularized bioscaffolds with potential for liver, kidney, pancreas, intestine and other organs' bioengineering. These bioscaffolds can further provide a tool to study cells in their natural three-dimensional environment, which is superior for drug discovery platform compared with cells cultured in two-dimensional petri dishes.
由于缺乏完整的血管网络，合成支架和天然衍生支架在实体器官生物工程中的应用受到了限制。在此，我们描述了一种具有完整血管树的生物支架系统的制造方法。将大小达30厘米的动物供体器官和组织用脱细胞溶液灌注，以选择性地去除组织的细胞成分，留下完整的细胞外基质和血管网络。血管树显示出液体依次通过中央入口血管流动，该血管分支成广泛的毛细血管床，然后合并回到单个出口血管。在一个例子中，即肝脏，我们使用中央入口血管通过生物支架灌注人源和动物肝细胞，以在体外创建功能性肝组织构建体。这些结果证明了一种新颖、简单且可扩展的方法，可获得具有肝脏、肾脏、胰腺、肠道和其他器官生物工程潜力的全器官血管化生物支架。这些生物支架还可以进一步提供一种工具，用于在其自然三维环境中研究细胞，与在二维培养皿中培养的细胞相比，这对于药物发现平台而言更具优势。
