Walker M, Morton J P
Centre for the Cellular Microenvironment, Advanced Research Centre, 11 Chapel Lane, James Watt School of Engineering, University of Glasgow, Glasgow, G11 6EW UK.
Cancer Research UK Scotland Institute, Garscube Estate, Switchback Rd, Glasgow, G61 1BD UK.
Biophys Rev. 2024 Dec 18;16(6):851-870. doi: 10.1007/s12551-024-01265-8. eCollection 2024 Dec.
Pancreatic adenocarcinoma (PDAC) is the predominant form of pancreatic cancer and one of the leading causes of cancer-related death worldwide, with an extremely poor prognosis after diagnosis. High mortality from PDAC arises partly due to late diagnosis resulting from a lack of early-stage biomarkers and due to chemotherapeutic drug resistance, which arises from a highly fibrotic stromal response known as desmoplasia. Desmoplasia alters tissue mechanics, which triggers changes in cell mechanosensing and leads to dysregulated transcriptional activity and disease phenotypes. Hydrogels are effective in vitro models to mimic mechanical changes in tissue mechanics during PDAC progression and to study the influence of these changes on mechanosensitive cell responses. Despite the complex biophysical changes that occur within the PDAC microenvironment, carefully designed hydrogels can very closely recapitulate these properties during PDAC progression. Hydrogels are relatively inexpensive, highly reproducible and can be designed in a humanised manner to increase their relevance for human PDAC studies. In vivo models have some limitations, including species-species differences, high variability, expense and legal/ethical considerations, which make hydrogel models a promising alternative. Here, we comprehensively review recent advancements in hydrogel bioengineering for developing our fundamental understanding of mechanobiology in PDAC, which is critical for informing advanced therapeutics.
胰腺腺癌（PDAC）是胰腺癌的主要形式，也是全球癌症相关死亡的主要原因之一，诊断后的预后极差。PDAC的高死亡率部分归因于缺乏早期生物标志物导致的诊断延迟，以及由一种称为促结缔组织增生的高度纤维化基质反应引起的化疗药物耐药性。促结缔组织增生改变了组织力学，触发细胞机械传感的变化，并导致转录活性失调和疾病表型。水凝胶是有效的体外模型，可模拟PDAC进展过程中组织力学的机械变化，并研究这些变化对机械敏感细胞反应的影响。尽管PDAC微环境中会发生复杂的生物物理变化，但精心设计的水凝胶在PDAC进展过程中可以非常接近地重现这些特性。水凝胶相对便宜，具有高度可重复性，并且可以以人性化的方式设计，以提高其与人类PDAC研究的相关性。体内模型存在一些局限性，包括种间差异、高变异性、成本以及法律/伦理考虑，这使得水凝胶模型成为一种有前景的替代方案。在此，我们全面综述了水凝胶生物工程的最新进展，以加深我们对PDAC机械生物学的基本理解，这对于指导先进治疗至关重要。
