Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays

Michelle Chadwick; Chen Yang; Liqiong Liu; Christian Moya Gamboa; Kelly Jara; Howon Lee; Hatem E Sabaawy

doi:10.1016/j.isci.2020.101365

Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays

iScience. 2020 Aug 21;23(8):101365. doi: 10.1016/j.isci.2020.101365. Epub 2020 Jul 13.

Authors

Michelle Chadwick¹, Chen Yang², Liqiong Liu¹, Christian Moya Gamboa¹, Kelly Jara¹, Howon Lee³, Hatem E Sabaawy⁴

Affiliations

¹ Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08901, USA.
² Department of Mechanical and Aerospace Engineering, Rutgers University - New Brunswick, New Brunswick, NJ 08901, USA.
³ Department of Mechanical and Aerospace Engineering, Rutgers University - New Brunswick, New Brunswick, NJ 08901, USA. Electronic address: howon.lee@rutgers.edu.
⁴ Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08901, USA; Departments of Medicine and Pathology and Laboratory Medicine, RBHS-Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA. Electronic address: sabaawhe@cinj.rutgers.edu.

Abstract

Glioblastoma is the most common and deadly primary brain malignancy. Despite advances in precision medicine oncology (PMO) allowing the identification of molecular vulnerabilities in glioblastoma, treatment options remain limited, and molecular assays guided by genomic and expression profiling to inform patient enrollment in life-saving trials are lacking. Here, we generate four-dimensional (4D) cell-culture arrays for rapid assessment of drug responses in glioblastoma patient-derived models. The arrays are 3D printed with thermo-responsive shape memory polymer (SMP). Upon heating, the SMP arrays self-transform in time from 3D cell-culture inserts into histological cassettes. We assess the utility of these arrays with glioblastoma cells, gliospheres, and patient derived organoid-like (PDO) models and demonstrate their use with glioblastoma PDOs for assessing drug sensitivity, on-target activity, and synergy in drug combinations. When including genomic and drug testing assays, this platform is poised to offer rapid functional drug assessments for future selection of therapies in PMO.

Keywords: Cancer; Medical Biotechnology; Tissue Engineering.

Abstract

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