Three-dimensional (3D) liver cell models - A Tool for Bridging the Gap Between Animal Studies and Clinical Trials When Screening Liver Accumulation and Toxicity of Nanobiomaterials

Abstract

Despite the exciting properties and wide-reaching applications in human health and medicine of nanobiomaterials (NBMs), their translation from bench to bedside is slow, with a predominant issue being liver accumulation and toxicity following systemic administration. In vitro 2D cell-based assays and in vivo testing are the most popular and widely used methods for assessing liver toxicity at preclinical stages, however these fall short in predicting toxicity for NBMs. Focusing on the in vitro and in vivo assessment, the accurate prediction of human-specific hepatotoxicity is still a significant challenge to researchers. This review describes such methods, focusing on the limitations they bring in the assessment of NBM hepatotoxicity, as one of the reasons defining the poor translation for NBMs. We will then present some of the most recent advances towards the development of more biologically relevant in vitro liver methods based on tissue-mimetic 3D cell models and how these could facilitate the translation NBM going forward. Finally, we also discuss the low public acceptance and limited uptake of tissue-mimetic 3D models in the pre-clinical assessment, despite the demonstrated technical and ethical advantages.

Pre-clinical 2D and 3D toxicity response to a panel of nanomaterials; comparative assessment of NBM-induced liver toxicity

“…2D and 3D cultures were exposed to AuNP, LipImage ™ 815, or various PACAs, using a variety of concentrations detailed below in Table 1 . The rationale behind the experimental design and the concentrations tested came from extensive dialogue and work we have undertaken within the REFINE project [ 27 ] and published degree thesis of Tutty, MA [ 28 ].…”

Application of 3D, 4D, 5D, and 6D bioprinting in cancer research: what does the future look like?

“…128 Some research revealed that cells in multicellular tumor spheroids (MCTS) are similarly or even more vulnerable to anticancer drugs than their 2D monolayer counterparts, despite the majority of studies demonstrating that cells in spheroids are more chemoresistant than cells in 2D monolayers. 129 For instance, it was demonstrated that both tumor cells grown in monolayer cell culture and tumor cells grown as multicellular spheroids were susceptible to the proteasome inhibitor PS-341's effects. 130 Spheroids are also more radioresistant than 2D monolayers, according to a number of studies.…”