Advanced bioengineering technologies for preclinical research

Abstract

Current in vitro practices must overcome important challenges to compare favorably with human studies. The limited applicability of conventional in vitro assays and strategies can be explained by the fact that standard approaches do not enable recapitulation of the complexity of human tissues and physiological functions. To address this challenge, novel bioengineering tools, techniques and technologies are rapidly emerging to advance current fundamental knowledge and innovate in vitro practices. For example, organs-on-a-chip have recently appeared as a small-scale solution to overcome the transability, financial and ethical concerns associated with animal studies in drug discovery and development. In parallel, biomimetic interfaces are increasingly recapitulating 3D structures with tissuelike dynamic properties to allow in-depth investigation of disease mechanisms. This review aims at highlighting current bioengineering approaches poised to address the shortcomings of conventional in vitro research practices towards the generation of more effective solutions for improving human health.

Organ on a Chip: A Novel in vitro Biomimetic Strategy in Amyotrophic Lateral Sclerosis (ALS) Modeling

“…Animal models are used widely since a long time ago to validate the preclinical results achieved by in vitro studies and to prepare them to be used in human beings. However, these models are expensive and bring up ethical matters ( 36 ). Also, some the animal models such as rodents require much time to generate and be investigated ( 55 , 56 ).…”

“…The nervous systems of Drosophila melanogaster and Caenorhabditis elegans are anatomically different from that of human beings and the CNS of zebrafish lacks upper motor neurons ( 55 , 56 , 65 ). On the other hand, the immune system of animals has shown significantly different responses when being exposed to new pharmaceutical agents ( 36 ). Animal models are not suitable to test multiple simultaneous hypotheses, as well.…”

“…With the advancement of bioengineering technologies, novel techniques and systems such as micro-physiological systems have emerged as revolutionary leading-edge technologies in biological and medical sciences. Organ on a chip (OOC) as an innovative bioengineering tool aims to provide a platform to promote new studies for discovering novel therapeutic approaches for different disorders ( 36 ). In ALS conditions, OOC not only helps to elucidate the mechanisms underlying the pathophysiology involved in ALS but also can be an effective step in the assessment and screening of new candidate drugs in drug discovery and development ( 37 ).…”

Biomaterials-based strategies for in vitro neural models

“…This disparity largely derives from the mismatch between the physiology of humans and animal models, 11 and the failure of current technologies to accurately recapitulate cell-and tissue-level functions. 12 Conventional in vitro approaches fall short of closing this gap because even though human-derived cells are available, the culture microenvironment causes substantial epigenetic and post-translational shifts resulting in cell behavior (e.g. morphological changes and migratory patterns, expression and activation of key molecules, availability of surface markers and cell-cell interactions) that do not accurately represent the complex and multifactorial nature of living tissues.…”

Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies

“…Human bioengineered in vitro tissues are emerging as new tools for preclinical research. 14 , 15 Specifically, bioengineered in vitro skeletal muscles would provide more efficient and predictive models to improve drug development for muscular dystrophies. Here, we discuss the recent advances in skeletal muscle tissue engineering, focusing on new human in vitro models for muscle analyses and their application in the study of muscular dystrophies.…”