Recent Advances on Cell Culture Platforms for In Vitro Drug Screening and Cell Therapies: From Conventional to Microfluidic Strategies

Abstract

The clinical translations of drugs and nanomedicines depend on coherent pharmaceutical research based on biologically accurate screening approaches. Since establishing the 2D in vitro cell culture method, the scientific community has improved cell-based drug screening assays and models. Those advances result in more informative biochemical assays and the development of 3D multicellular models to describe the biological complexity better and enhance the simulation of the in vivo microenvironment. Despite the overall dominance of conventional 2D and 3D cell macroscopic culture methods, they present physicochemical and operational challenges that impair the scale-up of drug screening by not allowing a high parallelization, multidrug combination, and high-throughput screening. Their combination and complementarity with microfluidic platforms enable the development of microfluidics-based cell culture platforms with unequivocal advantages in drug screening and cell therapies. Thus, this review presents an updated and consolidated view of cell culture miniaturization's physical, chemical, and operational considerations in the pharmaceutical research scenario. It clarifies advances in the field using gradient-based microfluidics, droplet-based microfluidics, printed-based microfluidics, digital-based microfluidics, SlipChip, and paper-based microfluidics. Finally, it presents a comparative analysis of the performance of cell-based methods in life research and development to achieve increased precision in the drug screening process.

Achieving Precision Healthcare through Nanomedicine and Enhanced Model Systems

“…While their advantages include being inexpensive, well established, ease of readout and with a plethora of scientific literature to compare results to, their lack of 3D-architecture, cell−cell and cell-matrix interactions, and with no mechanical forces or gradients, they fail to capture intricate biological dynamic processess. 31,32 Animal studies, mainly reliant on mice, better recapitulate the in vivo setting and have enabled researchers to determine NC circulation times, biodistribution, and efficacy. However, the misrepresentation of human anatomy and physiology has led to inconsistencies between animal data and clinical trial data, and intensifies the call to reduce animal testing and develop better and more clinically representative models.…”

“…Traditional in vitro cellular assays have been instrumental in studying NC delivery mechanisms and enabling large-scale NC screens. While their advantages include being inexpensive, well established, ease of readout and with a plethora of scientific literature to compare results to, their lack of 3D-architecture, cell–cell and cell-matrix interactions, and with no mechanical forces or gradients, they fail to capture intricate biological dynamic processess. , Animal studies, mainly reliant on mice, better recapitulate the in vivo setting and have enabled researchers to determine NC circulation times, biodistribution, and efficacy. However, the misrepresentation of human anatomy and physiology has led to inconsistencies between animal data and clinical trial data, and intensifies the call to reduce animal testing and develop better and more clinically representative models. ,− Recently, the obligation for animal testing has experienced an alleviation with the introduction of the Federal Food and Drug Administration (FDA) Modernization Act 2.0 in 2022, which encourages the use of novel model systems to help in evaluating mechanisms resulting in enhanced translatability.…”

Three‐dimensional multicellular biomaterial platforms for biomedical application

“…[17,18] Cells in the 2D multicellular platforms are evenly adherent to the wall with a single and defined cell morphology (slender and spreading cell morphology). [7] In contrast, cells in vivo are often adherent to the ECM with various types of morphology, and then are arranged in complex spatial structures along ECM fibers. The complex cell-ECM interaction also plays an important role in maintaining the physiological function of biological tissue.…”

“…The conventional multicellular in vitro platforms were always established in 2D conditions, in which cells are grown on standard polystyrene culture plates or Transwell chambers. [ 7 ] Because of its practicability, facilitation, and high repeatability, 2D multicellular platforms have become classic co‐culture methods. [ 8 ] Using the 2D multicellular platforms, researchers can easily culture cells, and then explore the relationships between different types of cells to understand cell crosstalk, [ 9 ] or assess the effects of one specific factor (such as cytokines, medicine, temperature, oxygen, electromagnetic fields, etc.)…”

Recent Progress in Fabrication of Electrospun Nanofiber Membranes for Developing Physiological In Vitro Organ/Tissue Models

“…Over the years, significant advances in developing cell culture platforms that mimic in vivo microenvironments have been developed and greatly contributed to the construction of in vitro organ/tissue models emulating in vivo physiology. [1,2] While DOI: 10.1002/mabi.202300244 traditional cell culture platforms have been limited to implementing only biochemical microenvironments through modulation of media composition or functionalization of extracellular matrix (ECM) components on substrates, advancements in cell culture platforms have made it possible to also implement the biophysical (mechanical and structural) microenvironments of in vivo tissues. [3,4] Recent studies presenting the importance of recapitulation of biophysical microenvironments for promoting cellular behaviors and functions [5][6][7] have greatly increased the need and interest in developing advanced cell culture platforms implementing both the biochemical and biophysical microenvironments.…”