Maintaining hepatic functional characteristics in-vitro is considered one of the main challenges in engineering liver tissue. As hepatocytes cultured ex-vivo are deprived of their native extracellular matrix (ECM) milieu, developing scaffolds that mimic the biomechanical and physicochemical properties of the native ECM is thought to be a promising approach for successful tissue engineering and regenerative medicine applications. On the basis that the decellularized liver matrix represents the ideal design template for engineering bioinspired hepatic scaffolds, to derive quantitative descriptors of liver ECM architecture, we characterised decellularised liver matrices in terms of their biochemical, viscoelastic and structural features along with porosity, permeability and wettability. Together, these data provide a unique set of quantitative design criteria which can be used to generate guidelines for fabricating biomaterial scaffolds for liver tissue engineering. As proof-of-concept, we investigated hepatic cell response to substrate viscoelasticity. On collagen hydrogels mimicking decellularised liver mechanics, cells showed superior morphology, higher viability and albumin secretion than on stiffer and less viscous substrates. Although scaffold properties are generally inspired by those of native tissues, our results indicate significant differences between the mechano-structural characteristics of untreated and decellularised hepatic tissue. Therefore, we suggest that design rules - such as mechanical properties and swelling behaviour - for engineering biomimetic scaffolds be re-examined through further studies on substrates matching the features of decellularized liver matrices.

在体外维持肝功能特征被认为是肝组织工程化的主要挑战之一。由于离体培养的肝细胞缺乏其天然细胞外基质 (ECM) 环境，因此开发模仿天然 ECM 生物力学和物理化学特性的支架被认为是成功组织工程和再生医学应用的一种有前途的方法。基于脱细胞肝基质代表了工程仿生肝支架的理想设计模板，为了导出肝脏 ECM 结构的定量描述符，我们从生化、粘弹性和结构特征以及孔隙率、渗透性和润湿性方面对脱细胞肝基质进行了表征。这些数据共同提供了一套独特的定量设计标准，可用于生成制造肝组织工程生物材料支架的指南。作为概念验证，我们研究了肝细胞对基质粘弹性的反应。在模仿脱细胞肝脏力学的胶原水凝胶上，细胞表现出比在更硬且粘度更低的基底上更好的形态、更高的活力和白蛋白分泌。尽管支架特性通常受到天然组织的启发，但我们的结果表明未经处理的肝组织和脱细胞肝组织的机械结构特征之间存在显着差异。因此，我们建议通过进一步研究与脱细胞肝基质特征相匹配的基材来重新审查工程仿生支架的设计规则，例如机械性能和膨胀行为。