The preparation of cell-containing microbubble scaffolds to mimic alveoli structure as a 3D drug-screening system for lung cancer
Journal
Biofabrication
Journal Volume
12
Journal Issue
2
Pages
25031
Date Issued
2020
Author(s)
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. ? 2020 IOP Publishing Ltd
SDGs
Other Subjects
Biocompatibility; Biological organs; Biomechanics; Cell culture; Cell death; Diseases; Drug products; Failure analysis; Microfluidics; Polymerase chain reaction; Pore size; Suspensions (fluids); 3-D cell culture; Anticancer drug discovery; Drug screening; Flow focusing; Lung Cancer; Microbial transglutaminase (mTGase); Physiological condition; Real time polymerase chain reactions; Scaffolds (biology); antineoplastic agent; biomaterial; deoxycytidine; gelatin; gemcitabine; protein bcl 2; A-549 cell line; cell culture technique; cell proliferation; cell survival; chemistry; compressive strength; devices; drug effect; genetics; human; lung tumor; metabolism; microbubble; pathology; procedures; tissue scaffold; A549 Cells; Antineoplastic Agents; Biocompatible Materials; Cell Culture Techniques; Cell Proliferation; Cell Survival; Compressive Strength; Deoxycytidine; Gelatin; Humans; Lung Neoplasms; Microbubbles; Proto-Oncogene Proteins c-bcl-2; Tissue Scaffolds
Type
journal article