Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening

Sci Rep. 2021 Jan 11;11(1):372. doi: 10.1038/s41598-020-79325-8.


A series of stable and ready-to-use bioinks have been developed based on the xeno-free and tunable hydrogel (VitroGel) system. Cell laden scaffold fabrication with optimized polysaccharide-based inks demonstrated that Ink H4 and RGD modified Ink H4-RGD had excellent rheological properties. Both bioinks were printable with 25-40 kPa extrusion pressure, showed 90% cell viability, shear-thinning and rapid shear recovery properties making them feasible for extrusion bioprinting without UV curing or temperature adjustment. Ink H4-RGD showed printability between 20 and 37 °C and the scaffolds remained stable for 15 days at temperature of 37 °C. 3D printed non-small-cell lung cancer (NSCLC) patient derived xenograft cells (PDCs) showed rapid spheroid growth of size around 500 µm in diameter and tumor microenvironment formation within 7 days. IC50 values demonstrated higher resistance of 3D spheroids to docetaxel (DTX), doxorubicin (DOX) and erlotinib compared to 2D monolayers of NSCLC-PDX, wild type triple negative breast cancer (MDA-MB-231 WT) and lung adenocarcinoma (HCC-827) cells. Results of flow property, shape fidelity, scaffold stability and biocompatibility of H4-RGD suggest that this hydrogel could be considered for 3D cell bioprinting and also for in-vitro tumor microenvironment development for high throughput screening of various anti-cancer drugs.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • A549 Cells
  • Animals
  • Bioprinting / methods*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cells, Cultured
  • Drug Screening Assays, Antitumor* / instrumentation
  • Drug Screening Assays, Antitumor* / methods
  • Humans
  • Hydrogels / chemistry*
  • Ink
  • Lung Neoplasms / pathology
  • Materials Testing
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Models, Biological
  • Neoplasms / pathology*
  • Polysaccharides / chemistry
  • Printing, Three-Dimensional
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry*
  • Tumor Microenvironment / physiology


  • Hydrogels
  • Polysaccharides