Microphysiological Systems: Next Generation Systems for Assessing Toxicity and Therapeutic Effects of Nanomaterials

Abstract

Nanomaterials (NMs) such as polymeric nanoparticles (NPs), vesicles, and dendrimers have revolutionized the biomedical field by enabling superior drug delivery, imaging, and sensing modalities. [1] The field of NMs is expected to grow tremendously as the nanotechnology market is projected to be worth $125 billion by 2024. [2] In addition, the increasing number of NMs used for diagnostic and therapeutic [3] purposes impose new restrictions on their intended effects and unwanted complications. We are continuously exposed to environmental pollutants through inhalation, [4] ingestion, [5] and dermal contact. [6] Many of these materials are ultrafine in size (<100 nm), which enables their facile entry and interaction Microphysiological systems, also known as organ-on-a-chip platforms, show promise for the development of new testing methods that can be more accurate than both conventional two-dimensional (2D) cultures and costly animal studies. The development of more intricate microphysiological systems can help to better mimic the human physiology and highlight the systemic effects of different drugs and materials. Nanomaterials are among a technologically important class of materials used for diagnostic, therapeutic, and monitoring purposes; all of which can be tested using new organ-on-a-chip systems. In addition, the toxicity of nanomaterials which have entered the body from ambient air or diet can have deleterious effects on various body systems. This in turn can be studied in newly developed microphysiological systems. While organ-on-a-chip models can be useful, they cannot pick up secondary and systemic toxicity. Thus, the utilization of multiorgan-on-a-chip systems for advancing nanotechnology will largely be reflected in the future of drug development, toxicology studies, and precision medicine. Various aspects of related studies, current challenges, and future perspectives are discussed in this paper.

Microfluidic Skin‐on‐a‐Chip Models: Toward Biomimetic Artificial Skin

“…[15] Precursory development of cell-based biosensors for drug and pathogen characterization opened the path for modeling the key functional units of organs in microfluidic platforms, later termed organ-on-chip (OoC). [15][16][17][18][19] Such platforms are aimed to reproduce the biological composition, function, and environment of native human tissue and bridge the gap between standard in vitro approaches and the human body. [20] This was demonstrated by reconstructing a physiologically relevant lung-on-a-chip capable of stretching and dynamically perfusing an alveolar-capillary interface model.…”

“…[9,19,20] However, their most powerful application comes when connected to multiple OoC devices to form a human-on-a-chip for assessing system-wide effects. [18] By more closely mimicking human tissue, SoC models promise true predictive abilities capable of limiting the number of drugs that successfully passed preclinical testing only to fail in clinical trials, and reducing the risk of eliminating drugs that are unsuccessful in animals but may be effective in humans. In this Review, a brief introduction to the anatomy and physiology of human skin with the view of highlighting key aspects that are required of a biomimetic skin model is provided, before discussing the current state-of-the-art fabrication techniques.…”

Advances in Microtechnology for Improved Cytotoxicity Assessment

“…For instance, the high surface-to-volume ratio of nanoparticles makes them highly reactive when compared to bulk materials (Recordati et al, 2015). Nanoparticles can penetrate cellular membranes, biological barriers and tissues, so they interact with biological systems at the molecular, cellular, organismal and ecosystem levels (Pietroiusti et al, 2018), The increasing interest of using nanoparticles in medicine, opens new possibilities for microtechnology, for instance to mimic whole organs (Organ-on-A-Chip technology), generating devices able to precisely study the effect of nanomaterials in a similar environment to in vivo (Ashammakhi et al, 2020).…”

“…Due to the high toxicity and barrier penetration capability of nanoparticles, the studies of their effects on three-dimensional environments, mimicking natural biosystems, enable more reliable approaches to evaluate the physiological effects of nanomaterials (Ashammakhi et al, 2020). For instance, Arends et al reported a microfluidic device to study the diffusion of nanoparticles through the basal layer, which is key to control the movement of nanoparticles between blood vessels and the surrounding extravascular space, observing a charge dependant accumulation of the species, similar to the one observed in vivo (Arends et al, 2015).…”

Microfluidic Devices: A New Paradigm in Toxicity Studies

“…In vitro experiments fail to control the exposure levels of nanomaterials and cannot take into account some physicochemical aspects, such as particle aggregation. Ashammakhi et al (2020) have proposed that microphysiological systems, especially multiorgan-ona-chip systems, which can be specifically designed to test the systemic toxicity, can be of use to evaluate the toxicity of nanomaterials [122]. The potential of microfluidic systems is evaluated for nanotoxicity research in various experiments.…”