The preparation of cell-containing microbubble scaffolds to mimic alveoli structure as a 3D drug-screening system for lung cancer

Abstract

Cancer is the leading cause of mortality worldwide, and lung cancer is the most malignant. However, the high failure rate in oncology drug development from in vitro studies to in vivo preclinical models indicates that the modern methods of evaluating drug efficacies in vitro are not reliable. Traditional 2D cell culture has proved inadequate to mimic real physiological conditions. Current 3D cell culture methods do not represent the delicate structure of lung alveoli. To mimic lung alveoli structure, a cell-containing enzyme-crosslinked gelatin microbubble scaffold was produced by mixing surfactant-containing gelatin solution with microbial transglutaminase (mTGase)-mixed A549 cell suspension in a four-channel flow-focusing microfluidic device. With uniform pore size of about 100 μm in diameter, this gelatin microbubble scaffold resembled the lung alveoli in structure and in mechanical properties with good biocompatibility. Effective gemcitabine concentration required to induce cell death in microbubble scaffolds was significantly higher than in 2D culture together with a longer treatment time. Cell death mechanisms were confirmed to be gemcitabine-induced cell apoptosis through Western blotting and real-time polymerase chain reaction. H&E staining and TUNEL assay showed rounded cells with DNA damage in drug-treated scaffolds. Taken together, the cell-containing microbubble scaffolds successfully mimicked lung alveoli in structure and cellular responses after gemcitabine treatment were similar to clinical regimen of treating lung carcinoma. The microbubble scaffold is promising to facilitate anticancer drug discovery by providing more accurate preclinical predictions.

The Potential Contribution of Biopolymeric Particles in Lung Tissue Regeneration of COVID-19 Patients

“…This highlights the significance of computational models in understanding cellular activity [122]. In addition, the cell responses to gemcitabine therapy were equivalent to those reported in clinical trials for lung carcinoma, showing that they may help design anticancer treatments by offering more accurate preclinical predictions [123]. PLGA is often used to create porous substrates for complex cell cultures.…”

Engineered Nanotopography on the Microfibers of 3D-Printed PCL Scaffolds to Modulate Cellular Responses and Establish an In Vitro Tumor Model

“…However, the predominant cell-ECM interactions in the native tissue microenvironment are missing in this model. Alternatively, hydrogel- or porous scaffold-based tumor models have been developed to culture A549 cells for tumor modeling and drug screening, which recapitulate the ECM microenvironment in vitro . , However, they are usually associated with low batch stability, poor reproducibility, and a high production cost because of the intrinsic instability of naturally derived biopolymers. Our EHD-printed scaffolds with fiber nanotopography is a promising platform to develop 3D tumor models for cancer research and drug screening applications.…”

Reconstruction of tumor microenvironment via in vitro three-dimensional models

“…Scaffolds with geometrically specified micro-patterns have enormous potential for studying fundamental cell biology. Multi-level manipulations for specialized and nano/micro-structured 3D substrates are feasible at single-cell resolution when these scaffolds are shaped as per required geometry [93][94][95][96][97][98][99]. For instance, using micro-nano manufacture, micropillar-microwell matrix arrays could be used for modeling intestinal tissues with lumen and crypt structures [93].…”