3D-Printable Gelatin Methacrylate-Xanthan Gum Hydrogel Bioink Enabling Human Induced Pluripotent Stem Cell Differentiation into Cardiomyocytes

Year: 2024

Authors: Deidda V., Ventisette I., Langione M., Giammarino L., Pioner J.M., Credi C., Carpi F.

Autors Affiliation: Univ Florence, Dept Ind Engn, I-50139 Florence, Italy; Univ Florence, Dept Expt & Clin Med, I-50134 Florence, Italy; Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, I-50139 Florence, Italy; Univ Florence, Dept Biol, I-50019 Sesto Fiorentino, Italy; Univ Florence, European Lab Nonlinear Spect, I-50019 Sesto Fiorentino, Italy; CNR, Natl Inst Opt, I-50019 Sesto Fiorentino, Italy.

Abstract: We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using a gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at a low concentration (5% w/v) allows for the growth of diverse cells, its 3D printability has been found to be limited by its low viscosity. To overcome that drawback, making the hydrogel both compatible with hiPSCs and 3D-printable, we developed an extrudable GelMA-based bioink by adding xanthan gum (XG). The GelMA-XG composite hydrogel had an elastic modulus (similar to 9 kPa) comparable to that of cardiac tissue, and enabled 3D printing with high values of printing accuracy (83%) and printability (0.98). Tests with hiPSCs showed the hydrogel’s ability to promote their proliferation within both 2D and 3D cell cultures. The tests also showed that hiPSCs inside hemispheres of the hydrogel were able to differentiate into cardiomyocytes, capable of spontaneous contractions (average frequency of similar to 0.5 Hz and amplitude of similar to 2%). Furthermore, bioprinting tests proved the possibility of fabricating 3D constructs of the hiPSC-laden hydrogel, with well-defined line widths (similar to 800 mu m).

Journal/Review: JOURNAL OF FUNCTIONAL BIOMATERIALS

Volume: 15 (10)      Pages from: 297-1  to: 297-17

More Information: This research was funded by the Italian Ministry of University and Research (PNRR project AGE-IT-Ageing well in an ageing society (F.C.), PNRR project Integrated infrastructure initiative in photonic and quantum sciencesI-PHOQS (C.C.) and PRIN2022 project 20223L2C9N The Role of Cardiac Extracellular matrix-Cell interaction in the onset of dystrophic cardiomyopathies (MALADAPT) (J.M.P.)), the Italian Ministry of Health (project GR-2021-12375403 Precision medicine in dystrophin cardiomyopathies-cha racterization of induced pluripotent stem cells (iPSC) derived from Duchenne patients with advanced heart failure using artificial intelligence to differentiate disease pathways and identify predictors for treatment response (J.M.P.)) and by Fondazione Cassa di Risparmio di Firenze, Italy (project Lab Didattici Ingegneria Biomedica (F.C.)).
KeyWords: 3D bioprinting; hydrogel; HiPSCs; gelatin; GelMA; xanthan gum; cardiac; tissue engineering
DOI: 10.3390/jfb15100297