Recent Advances in the Microfluidic Platform for Programming Cell-Based Biomaterials

Microfluidic Platforms Promote the Development of Cell-Based Living Materials

Cell-based living materials, including single cells, cell-loaded fibers, cell sheets, organoids, and organs, have been considered dynamic functional units or active building blocks with promise in many biomedical fields. A typical example is the reprogramming of chimeric antigen receptor (CAR) T cells, which represent a promising cell-based immunotherapy strategy and have made explosive progress in the field of cancer treatment. 

In the pharmaceutical industry, the development of new therapeutic drugs requires extensive preclinical evaluation, which currently relies heavily on the use of animal models, resulting in inefficiencies and high costs. Human cell-derived tissue and organ models can replicate the functions of native human tissues and organs, offering great potential for high-throughput, accurate, reliable, and cost-effective preclinical drug screening and understanding the in vitro biological basis of diseases by replacing traditional animal models. 

The recreation of these tissue and organ models typically depends on the assembly of cell-based living materials, such as individual cells, cellular fibers, or cell sheets. The immense demand for cell-based living materials drives the programming of such materials, including editing the phenotypes and genotypes of single cells, constructing simple (e.g., cellular fibers or cell sheets) or complex (e.g., organoids or organs) functional units from individual cells, and adopting advanced bioengineering strategies to construct these units in a high-throughput, scalable, and efficient manner.

Microfluidic platforms, which can precisely manipulate fluids at the micron scale, are considered powerful and robust tools to meet the aforementioned demand. Over the past two decades, significant advancements in materials and micromachining technologies have made the design and manufacturing of low-cost and high-fidelity new microfluidic platforms possible. 

The inherent advantages of microfluidic platforms make them attractive candidates for cell-based biomedical research. For instance, one of their most important features is that the size of channels, chambers, or structures in microfluidic platforms can be as small as that of individual cells, allowing for high-throughput and precise handling of individual cells. Compared to traditional methods, microfluidic platforms can more efficiently recreate environments resembling the physiological conditions required for long-term in vitro cell culture and tissue function regeneration, such as oxygen gradients, complex fluid flows, and cyclic mechanical deformations. Utilizing these unique characteristics, researchers in the fields of materials, engineering, and life sciences have used microfluidic platforms to significantly promote the development of cell-based living materials for cancer immunotherapy, regenerative medicine, drug development, among other fields.

Microfluidic Platform Designs for Programming Cell-Based Biomaterials

Given the significance of microfluidic platforms in various biomedical fields, a substantial number of excellent reviews have been conducted on the advancements of single-cell, organoid, or organ programming microfluidic platforms, providing insightful guidance to researchers in related fields. Notably, there has yet to be a review article on how to design microfluidic platforms to program cell-based biomaterials from single cells to complex organs. Researchers have looked ahead to the microfluidic platforms for programming cell-based biomaterials.