仿生多腔室微流控肝小叶

Biomimetic Liver Lobules from Multi-Compartmental Microfluidics.

机构信息

Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.

Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.

出版信息

Adv Sci (Weinh). 2024 Nov;11(42):e2406573. doi: 10.1002/advs.202406573. Epub 2024 Sep 19.

Abstract

Engineered liver lobule is highly practical in hepatic disease treatment, while constructing a 3D biomimetic lobule with a heterogeneous architecture on a large scale is challenging. Here, inspired by the natural architectural construction of hepatic lobules, biomimetic hepatic lobules are proposed with coaxially through-pores for nutrient exchange via microfluidic technology. This multi-channel microfluidic chip is made by parallelly installing capillaries. Sodium alginate (Alg) is pumped through its central channel, while Ca-loaded gelatin methacrylate (GelMA) solutions encapsulating hepatocytes, mesenchymal stem cells, and endothelia cells are pumped through surrounding channels, respectively. The rapid gelation of Alg and Ca brings about an in situ formation of Alg fiber, with heterogeneous multi-cell-laden GelMA microcarriers forming around it. The peeled-off microcarriers each featured with a coaxially through pore, simulating the cord-like structure of hepatic lobule and facilitating nutrients exchange. Meanwhile, the spatially anisotropic arrangement of cells highly simulates the hepatic architecture. It is demonstrated that by transplanting these biomimetic microparticles into liver in situ, the failed liver in rat shows increased regeneration and decreased necrosis. These results indicated that the microfluidic multi-compartmental microcarriers provide a new strategy to engineer 3D artificial livers for clinical translation.

摘要

工程化肝小叶在肝脏疾病治疗中具有很高的实用性,然而,在大规模上构建具有异质结构的 3D 仿生肝小叶仍然具有挑战性。在这里,受肝小叶自然结构构建的启发,通过微流控技术提出了具有同轴贯穿孔的仿生肝小叶,用于营养物质交换。这种多通道微流控芯片通过平行安装毛细管来制作。将海藻酸钠(Alg)通过其中心通道泵送,同时将负载钙的明胶甲基丙烯酰胺(GelMA)溶液分别通过周围通道泵送,其中包封有肝细胞、间充质干细胞和内皮细胞。Alg 和 Ca 的快速凝胶化导致 Alg 纤维的原位形成,带有异质多细胞负载的 GelMA 微载体围绕其形成。剥离的微载体每个都具有同轴贯穿孔,模拟肝小叶的索状结构并促进营养物质交换。同时,细胞的空间各向异性排列高度模拟了肝组织的结构。研究表明,将这些仿生微颗粒原位移植到肝脏中,大鼠的失效肝脏显示出增加的再生和减少的坏死。这些结果表明,微流控多腔室微载体为临床转化提供了构建 3D 人工肝脏的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56d9/11558095/bb9aa238599d/ADVS-11-2406573-g005.jpg

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