PDF(Pubmed)
Abstract：
The paper highlights how significant characteristics of liver can be modeled in tissue-engineered constructs using unconventional scaffolds. Hepatic lobular organization and metabolic zonation can be mimicked with decellularized plant structures with vasculature resembling a native-hepatic lobule vascular arrangement or silk blend scaffolds meticulously designed for guided cellular arrangement as hepatic patches or metabolic activities. The functionality of hepatocytes can be enhanced and maintained for long periods in naturally fibrous structures paving way for bioartificial liver development. The phase I enzymatic activity in hepatic models can be raised exploiting the microfibrillar structure of paper to allow cellular stacking creating hypoxic conditions to induce in vivo-like xenobiotic metabolism. Lastly, the paper introduces amalgamation of carbon-based nanomaterials into existing scaffolds in liver tissue engineering.
Unconventional scaffolds have the potential to meet the current challenges in liver tissue engineering- loss of hepatic morphology and functions over long-term culture, absence of native-like cell-cell and cell-matrix interactions, organization of hepatocytes into lobular structures exhibiting metabolic variations-which hinder pharmaceutical analysis, regenerative therapies and artificial organ development. Paper with cellulose microfibril network develops cellular aggregates with hypoxic conditions that influence enzymes of xenobiotic metabolism proving to be a better scaffold for hepatotoxicity testing compared with conventional monolayers in tissue culture plates. Decellularized plant stems provide already-built vasculature to be exploited for the development of intricate vessel networks that exist in hepatic lobules aiding in regenerative medicine for hepatic pathologies. Fibrous plant structures are excellent materials for the immobilization of hepatocytes and improve albumin secretion enabling their use in bioartificial liver development. Biomimicry of metabolic zonation in hepatic lobules can be achieved with perfusion culture using silk blend scaffolds with varying proportions of the liver matrix that orchestrate cellular function. The mechanical properties of silk allow the fabrication of structures that resemble liver anatomy to generate native-like hepatic lobules. Nanomaterials have immense potential as a component of composite material development for scaffolds to achieve improved predictive ability in pharmacokinetics. Most of these unconventional scaffolds have the added advantage of being readily available, accessible, affordable and sustainable for liver tissue engineering applications. Conclusively, the shift of attention away from conventional scaffolds poses a promising future in the field of tissue engineering.
Unconventional scaffolds have the potential to meet the current challenges in liver tissue engineering- loss of hepatic morphology and functions over long-term culture, absence of native-like cell-cell and cell-matrix interactions, organization of hepatocytes into lobular structures exhibiting metabolic variations-which hinder pharmaceutical analysis, regenerative therapies and artificial organ development. Paper with cellulose microfibril network develops cellular aggregates with hypoxic conditions that influence enzymes of xenobiotic metabolism proving to be a better scaffold for hepatotoxicity testing compared with conventional monolayers in tissue culture plates. Decellularized plant stems provide already-built vasculature to be exploited for the development of intricate vessel networks that exist in hepatic lobules aiding in regenerative medicine for hepatic pathologies. Fibrous plant structures are excellent materials for the immobilization of hepatocytes and improve albumin secretion enabling their use in bioartificial liver development. Biomimicry of metabolic zonation in hepatic lobules can be achieved with perfusion culture using silk blend scaffolds with varying proportions of the liver matrix that orchestrate cellular function. The mechanical properties of silk allow the fabrication of structures that resemble liver anatomy to generate native-like hepatic lobules. Nanomaterials have immense potential as a component of composite material development for scaffolds to achieve improved predictive ability in pharmacokinetics. Most of these unconventional scaffolds have the added advantage of being readily available, accessible, affordable and sustainable for liver tissue engineering applications. Conclusively, the shift of attention away from conventional scaffolds poses a promising future in the field of tissue engineering.
摘要：
本文强调了如何使用非常规支架在组织工程构建体中对肝脏的重要特征进行建模。肝小叶组织和代谢分区可以用脱细胞植物结构模拟，其脉管系统类似于天然肝小叶血管排列或为指导细胞排列而精心设计的丝混合支架，如肝脏斑块或代谢活动。肝细胞的功能可以在天然纤维结构中得到增强并长期维持，为生物人工肝的发育铺平了道路。可以利用纸的微纤维结构来提高肝模型中的I相酶活性，以允许细胞堆积产生低氧条件，从而诱导体内样的异种生物代谢。最后,本文介绍了将碳基纳米材料合并到肝组织工程中现有的支架中。
非常规支架有可能应对当前肝组织工程中的挑战-长期培养后肝形态和功能的丧失。缺乏天然样细胞-细胞和细胞-基质相互作用，肝细胞的组织成小叶结构表现出代谢变异-这阻碍了药物分析，再生疗法和人工器官发育。与组织培养板中的常规单层相比，具有纤维素微纤丝网络的纸在缺氧条件下会形成细胞聚集体，从而影响异生代谢酶，这被证明是用于肝毒性测试的更好支架。脱细胞的植物茎提供了已经建立的脉管系统，可用于开发存在于肝小叶中的复杂血管网络，从而有助于肝脏病理学的再生医学。纤维植物结构是用于固定肝细胞和改善白蛋白分泌的优异材料,使得它们能够用于生物人工肝发育。肝小叶中代谢分区的仿生可以通过使用具有不同比例的协调细胞功能的肝基质的丝混合支架的灌注培养来实现。丝的机械性能允许制造类似于肝脏解剖结构的结构以产生天然样的肝小叶。纳米材料作为支架复合材料开发的组成部分具有巨大的潜力，可以提高药代动力学的预测能力。这些非常规支架中的大多数具有易于获得的附加优点，可访问,负担得起的和可持续的肝脏组织工程应用。最后，注意力从传统支架的转移为组织工程领域带来了光明的未来。
非常规支架有可能应对当前肝组织工程中的挑战-长期培养后肝形态和功能的丧失。缺乏天然样细胞-细胞和细胞-基质相互作用，肝细胞的组织成小叶结构表现出代谢变异-这阻碍了药物分析，再生疗法和人工器官发育。与组织培养板中的常规单层相比，具有纤维素微纤丝网络的纸在缺氧条件下会形成细胞聚集体，从而影响异生代谢酶，这被证明是用于肝毒性测试的更好支架。脱细胞的植物茎提供了已经建立的脉管系统，可用于开发存在于肝小叶中的复杂血管网络，从而有助于肝脏病理学的再生医学。纤维植物结构是用于固定肝细胞和改善白蛋白分泌的优异材料,使得它们能够用于生物人工肝发育。肝小叶中代谢分区的仿生可以通过使用具有不同比例的协调细胞功能的肝基质的丝混合支架的灌注培养来实现。丝的机械性能允许制造类似于肝脏解剖结构的结构以产生天然样的肝小叶。纳米材料作为支架复合材料开发的组成部分具有巨大的潜力，可以提高药代动力学的预测能力。这些非常规支架中的大多数具有易于获得的附加优点，可访问,负担得起的和可持续的肝脏组织工程应用。最后，注意力从传统支架的转移为组织工程领域带来了光明的未来。
