High Throughput Bioprinting Using Decellularized Adipose Tissue‐Based Hydrogels for 3D Breast Cancer Modeling

Abstract

Abstract3D bioprinting allows rapid automated fabrication and can be applied for high throughput generation of biomimetic constructs for in vitro drug screening. Decellularized extracellular matrix (dECM) hydrogel is a popular biomaterial choice for tissue engineering and studying carcinogenesis as a tumor microenvironmental mimetic. This study proposes a method for high throughput bioprinting with decellularized adipose tissue (DAT) based hydrogels for 3D breast cancer modeling. A comparative analysis of decellularization protocol using detergent‐based and detergent‐free decellularization methods for caprine‐origin adipose tissue is performed, and the efficacy of dECM hydrogel for 3D cancer modeling is assessed. Histological, biochemical, morphological, and biological characterization and analysis showcase the cytocompatibility of DAT hydrogel. The rheological property of DAT hydrogel and printing process optimization is assessed to select a bioprinting window to attain 3D breast cancer models. The bioprinted tissues are characterized for cellular viability and tumor cell‐matrix interactions. Additionally, an approach for breast cancer modeling is shown by performing rapid high throughput bioprinting in a 96‐well plate format, and in vitro drug screening using 5‐fluorouracil is performed on 3D bioprinted microtumors. The results of this study suggest that high throughput bioprinting of cancer models can potentially have downstream clinical applications like multi‐drug screening platforms and personalized disease models.

Assessment and process optimization of high throughput biofabrication of immunocompetent breast cancer model for drug screening applications

“…Effective removal of cellular debris and lipids associated with adipose tissue is necessary to prevent immunogenic reactions during cell culturebased experiments. Based on our research group's recent study [62], 62.385% ± 2.884% of hydroxyproline content and 80.606% ± 1.647% of sulfated GAGs are retained in our non-detergent DAT compared to native adipose tissue, while the DNA content for our decellularized tissue was below 50 ng mg −1 of lyophilized tissue.…”

“…We DAT using the non-detergent-based decellularization method as previously optimized and discussed elsewhere [62]. Briefly, caprine omental adipose tissue was obtained from a slaughterhouse.…”