The vasculature plays a critical role in cancer progression and metastasis, representing a pivotal aspect in the creation of cancer models. In recent years, the emergence of organ-on-a-chip technology has proven to be a robust tool, capable of replicating in vivo conditions with exceptional spatiotemporal resolution, making it a significant asset in cancer research. This review delves into the latest developments in 3D microfluidic vascularized tumor models and their applications in vitro, focusing on heterotypic cellular interactions, the mechanisms of metastasis, and therapeutic screening. Additionally, the review examines the benefits and drawbacks of these models, as well as the future prospects for their advancement.

Collagen is an important material for biomedical research, but using mammalian tissue-derived collagen carries the risk of zoonotic disease transmission. Marine organisms, such as farmed tilapia, have emerged as a safe alternative source of collagen for biomedical research. However, the tilapia collagen products for biomedical research are rare, and their biological functions remain largely unexamined. In this study, we characterized a commercial tilapia skin collagen using SDS-PAGE and fibril formation assays and evaluated its effects on skin fibroblast adhesion, proliferation, and migration, comparing it with commercial collagen from rat tails, porcine skin, and bovine skin. The results showed that tilapia skin collagen is a type I collagen, similar to rat tail collagen, and has a faster fibril formation rate and better-promoting effects on cell migration than porcine and bovine skin collagen. We also confirmed its application in a 3D culture for kidney cells’ spherical cyst formation, fibroblast-induced gel contraction, and tumor spheroid interfacial invasion. Furthermore, we demonstrated that the freeze-dried tilapia skin collagen scaffold improved wound closure in a mouse excisional wound model, similar to commercial porcine or bovine collagen wound dressings. In conclusion, tilapia skin collagen is an ideal biomaterial for biomedical research.

Despite several extraordinary improvements in cancer immunotherapy, its therapeutic effectiveness against many distinct cancer types remains mostly limited and requires further study. Different microfluidic-based cancer immunotherapy-on-a-chip (ITOC) systems have been developed to help researchers replicate the tumor microenvironment and immune system. Numerous microfluidic platforms can potentially be used to perform various on-chip activities related to early clinical cancer immunotherapy processes, such as improving immune checkpoint blockade therapy, studying immune cell dynamics, evaluating cytotoxicity, and creating vaccines or organoid models from patient samples. In this review, we summarize the most recent advancements in the development of various microfluidic-based ITOC devices for cancer treatment niches and present future perspectives on microfluidic devices for immunotherapy research.

CO₂ laser manufacturing has served as an enabling and reliable tool for rapid and cost-effective microfabrication over the past few decades. While a wide range of industrial and biological applications have been studied, the choice of materials fabricated across various laser parameters and systems is often confounded by their complex combinations. We herein presented a unified procedure performed using percussion CO₂ laser drilling with a range of laser parameters, substrate materials and various generated microstructures, enabling a variety of downstream tissue/cellular-based applications. Emphasis is placed on delineating the laser drilling effect on different biocompatible materials and proof-of-concept utilities. First, a polydimethylsiloxane (PDMS) microneedle (MN) array mold is fabricated to generate dissolvable polyvinylpyrrolidone/polyvinyl alcohol (PVP/PVA) MNs for transdermal drug delivery. Second, polystyrene (PS) microwells are optimized in a compact array for the formation of size-controlled multicellular tumor spheroids (MCTSs). Third, coverglass is perforated to form a microaperture that can be used to trap/position cells/spheroids. Fourth, the creation of through-holes in PS is validated as an accessible method to create channels that facilitate medium exchange in hanging drop arrays and as a conducive tool for the growth and drug screenings of MCTSs.

3D multicellular tumor spheroids (MCTSs) have recently emerged as a landmark for cancer research due to their inherent traits that are physiologically relevant to primary tumor microenvironments. A facile approach–laser‐ablated micro U‐wells–has been widely adopted in the past decade. However, the differentiation of microwell uniformities and the construction of arrays have all remained elusive. Herein, an improved laser‐ablated microwell array technique is proposed that can not only achieve arrayed MCTSs with identical sizes but can also perform high‐throughput drug assessments in situ. Three critical laser ablation parameters, including frequency, duty cycle, and pulse number, are investigated to generate microwells flexibly with a range from 170 to 400 μm. The choice of microwells is optimally arranged into an array via precise control of horizontal spacing (d_x) and vertical spacing (d_y) amenable of cell‐loss‐free culture during cell seeding. Harvested T24, A549 and Huh‐7 MCTSs from the microwell array correspond to approximately 75 to 140 μm in diameter. Anticancer drug screening of cisplatin validated IC50 values in 2D and MCTS conditions are 3.5 versus 9.1 μM (T24), 11.8 versus 277.7 μM (A549) and 33.5 versus 52.8 μM (Huh‐7), and the permeability is measured to range from 0.042 to 0.58 μm min⁻¹.

Metastasis is the leading cause of cancer-related deaths. During this process, cancer cells are likely to navigate discrete tissue-tissue interfaces, enabling them to infiltrate and spread throughout the body. Three-dimensional (3D) spheroid modeling is receiving more attention due to its strengths in studying the invasive behavior of metastatic cancer cells. While microscopy is a conventional approach for investigating 3D invasion, post-invasion image analysis, which is a time-consuming process, remains a significant challenge for researchers. In this study, we presented an image processing pipeline that utilized a deep learning (DL) solution, with an encoder-decoder architecture, to assess and characterize the invasion dynamics of tumor spheroids. The developed models, equipped with feature extraction and measurement capabilities, could be successfully utilized for the automated segmentation of the invasive protrusions as well as the core region of spheroids situated within interfacial microenvironments with distinct mechanochemical factors. Our findings suggest that a combination of the spheroid culture and DL-based image analysis enable identification of time-lapse migratory patterns for tumor spheroids above matrix-substrate interfaces, thus paving the foundation for delineating the mechanism of local invasion during cancer metastasis.