3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays

Abstract

Tumor-on-chips have become an effective resource in cancer research. However, their widespread use remains limited due to issues related to their practicality in fabrication and use. To address some of these limitations, we introduce a 3D-printed chip, which is large enough to host ~1 cm3 of tissue and fosters well-mixed conditions in the liquid niche, while still enabling the formation of the concentration profiles that occur in real tissues due to diffusive transport. We compared the mass transport performance in its rhomboidal culture chamber when empty, when filled with GelMA/alginate hydrogel microbeads, or when occupied with a monolithic piece of hydrogel with a central channel, allowing communication between the inlet and outlet. We show that our chip filled with hydrogel microspheres in the culture chamber promotes adequate mixing and enhanced distribution of culture media. In proof-of-concept pharmacological assays, we biofabricated hydrogel microspheres containing embedded Caco2 cells, which developed into microtumors. Microtumors cultured in the device developed throughout the 10-day culture showing >75% of viability. Microtumors subjected to 5-fluorouracil treatment displayed <20% cell survival and lower VEGF-A and E-cadherin expression than untreated controls. Overall, our tumor-on-chip device proved suitable for studying cancer biology and performing drug response assays.

Bio-Inspired Nanomaterials for Micro/Nanodevices: A New Era in Biomedical Applications

“…Figure 23 depicts the basic components of a common TOC. The utilization of a tumor-on-chip system fabricated through 3D printing techniques facilitated the cultivation of cells for an extended duration, thereby replicating the intricate process of nutrient and anti-cancer drug transportation within authentic TMEs [ 380 ]. The analysis of convective and diffusive transport within the culture chamber was conducted by employing a fluorescent tracer.…”

A 3D-printed tumor-on-chip: user-friendly platform for the culture of breast cancer spheroids and the evaluation of anti-cancer drugs

“…flows conveying culture media, drugs, oxygen, chemical factors, etc.) [12,13] with the aim of emulating relevant aspects of tumor physiology. ToCs have become an important resource in biomedical research [9,11], and many relevant examples of their applications have been published recently [9,10,12,[14][15][16][17].…”

“…[12,13] with the aim of emulating relevant aspects of tumor physiology. ToCs have become an important resource in biomedical research [9,11], and many relevant examples of their applications have been published recently [9,10,12,[14][15][16][17]. ToCs can be used to conduct fundamental studies related to human cancerous tissues [8,10] and to assess the efficacy or toxicity of anti-cancer drugs [12,[15][16][17].…”

“…ToCs have become an important resource in biomedical research [9,11], and many relevant examples of their applications have been published recently [9,10,12,[14][15][16][17]. ToCs can be used to conduct fundamental studies related to human cancerous tissues [8,10] and to assess the efficacy or toxicity of anti-cancer drugs [12,[15][16][17]. These platforms may also be powerful enablers of personalized medicine in the near future [18][19][20].…”

“…ToCs are built mainly by assembling multiple layers of poly(methyl methacrylate) (PMMA), using screws or by casting polydimethylsiloxane (PDMS) in 3D-printed molds, and these features lead to problems associated with leakage and contamination [10,[31][32][33]. Only recently has 3D printing been used to fabricate microfluidic devices for diverse applications, including cell culture and organ-on-chips or ToCs [12,13,30,34]. In principle, 3D printing can greatly simplify the cycle of designing, prototyping, and testing new microfluidic devices.…”