![]() This will lead to the discovery of optimum and efficient radio/chemotherapy parameters and the development of state of the art cancer therapeutic strategies ( Aggarwal et al., 2009). The proper design of cell culture conditions for cancer research is crucial to achieve better understanding of tumor biology. Therefore, implementation of custom-designed biomaterial scaffolds instead of conventional monolayer tissue culture models can promise more reliable therapeutic feedback ( Liu and Vunjak-Novakovic, 2016). Tumor cells communicate with their microenvironment in a very dynamic and reciprocal way. The employment of tissue engineering technologies for cancer biology has been appealing, as they provide a suitable milieu that can regulate tumor development and progression, and metastasis thereof. A high demand for developing innovative, reliable, and consistent models for drug testing and hepatotoxicity research is existent ( Hughes, 2008). Cell-based assays are used in the investigations to gain insights into cellular responses to various drugs in an inexpensive, time-effective, and scalable manner ( Lovitt et al., 2014). In this regard, discovery, and validation of new, effective anticancer drugs for both chemotherapy and daily medication have been diligently pursued. Considerable efforts have been carried out towards the development of efficient cancer treatments. Liver cancer was predicted to be the cause of 830,000 deaths in 2020 ( Sung et al., 2021). Liver cancer is one of the most prevalent types of cancer that is ranked fourth among the main causes of cancer-related deaths across the world. Taken together, this new cellulosic 3D scaffold can be confidently proposed for chemotherapeutic testing of drugs on hepatocellular carcinoma. Moreover, prilocaine, an anticancer drug, showed a higher effectiveness against the cancer cells cultured on the 3D DTL scaffold, compared to a 2D platform. The cells exhibited a higher growth and proliferation rate within the DTL scaffold, as verified by quantifying the expression of related genes, DAPI staining, and SEM imaging of the cells. The surface hydrophilicity, mechanical properties, and topography measurement and molecular analyses revealed that the 3D DTL scaffold is an ideal candidate for liver cancer modeling. Here, we developed a novel 3D natural scaffold made from decellularized tomato hairy leaves (hereafter called as DTL) to mimic the microenvironment of human hepatocellular carcinoma (HCC) for pharmaceutical purposes. ![]() In this regard, decellularized plant tissues can perform as suitable 3D scaffolds for mammalian cell culture to create a near-to-real condition to test drug efficacy. ![]() Considering the significant contribution of tumor microenvironment to cell’s response to medications, in vitro 3D bioinspiration of cancer cell niches can be regarded as an advanced strategy to improve the accuracy and reliability of the drug-based treatment. To achieve reliable therapeutic effects, it is crucial to develop efficient approaches to test novel anticancer drugs. Liver cancer is now one of the main causes leading to death worldwide.
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