Investigating the Role of Sustained Calcium Release in Silk-Gelatin-Based Three-Dimensional Bioprinted Constructs for Enhancing the Osteogenic Differentiation of Human Bone Marrow Derived Mesenchymal Stromal Cells

Aarushi Sharma, Giovanna Desando, Mauro Petretta, Shikha Chawla, Isabella Bartolotti, Cristina Manferdini, Francesca Paolella, Elena Gabusi, Diego Trucco, Sourabh Ghosh, Gina Lisignoli

Research output: Contribution to journalArticlepeer-review

Abstract

Scaffold-based bone tissue engineering strategies fail to meet the clinical need to fabricate patient-specific and defect shape-specific, anatomically relevant load-bearing bone constructs. 3D bioprinting strategies are gaining major interest as a potential alternative, but design of a specific bioink is still a major challenge that can modulate key signaling pathways to induce osteogenic differentiation of progenitor cells, as well as offer appropriate microenvironment to augment mineralization. In the present study, we developed silk fibroin protein and gelatin-based conjugated bioink, which showed localized presence and sustained release of calcium. Presence of 2.6 mM Ca 2+ ions within the bioink could further induce enhanced osteogenesis of Bone marrow derived progenitor cells (hMSCs) compared to the bioink without calcium, or same concentration of calcium added to the media, as evidenced by upregulated gene expression of osteogenic markers. This study generated unprecedented mechanistic insights on the role of fibroin-gelatin-CaCl 2 bioink in modulating expression of several proteins which are known to play crucial role in bone regeneration as well as key signaling pathways such as β-catenin, BMP signaling pathway, Parathyroid hormone-dependent signaling pathway, Forkhead box O (FOXO) pathway, and Hippo pathways in hMSC-laden bioprinted constructs.

Original languageEnglish
Pages (from-to)1518-1533
Number of pages16
JournalACS Biomaterials Science and Engineering
Volume5
Issue number3
DOIs
Publication statusPublished - Feb 12 2019

Keywords

  • 3D bioprinting
  • extracellular calcium
  • osteogenesis
  • signaling pathways
  • silk bioink

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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