One-Step Bioprinting of Multi-Channel Hydrogel Filaments Using Chaotic Advection: Fabrication of Pre-Vascularized Muscle-Like Tissues

Edna Johana Bolívar-Monsalve, Carlos Fernando Ceballos-González, Carolina Chávez-Madero, Brenda Guadalupe de la Cruz-Rivas, Silvana Velásquez Marín, Shirley Mora-Godínez, Luisa María Reyes-Cortés, Ali Khademhosseini, Paul S. Weiss, Mohamadmahdi Samandari, Ali Tamayol, Mario Moisés Alvarez, Grissel Trujillo-de Santiago

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The biofabrication of living constructs containing hollow channels is critical for manufacturing thick tissues. However, current technologies are limited in their effectiveness in the fabrication of channels with diameters smaller than hundreds of micrometers. It is demonstrated that the co-extrusion of cell-laden hydrogels and sacrificial materials through printheads containing Kenics static mixing elements enables the continuous and one-step fabrication of thin hydrogel filaments (1 mm in diameter) containing dozens of hollow microchannels with widths as small as a single cell. Pre-vascularized skeletal muscle-like filaments are bioprinted by loading murine myoblasts (C2C12 cells) in gelatin methacryloyl - alginate hydrogels and using hydroxyethyl cellulose as a sacrificial material. Higher viability and metabolic activity are observed in filaments with hollow multi-channels than in solid constructs. The presence of hollow channels promotes the expression of Ki67 (a proliferation biomarker), mitigates the expression of hypoxia-inducible factor 1-alpha, and markedly enhances cell alignment (i.e., 82% of muscle myofibrils aligned (in ±10°) to the main direction of the microchannels after seven days of culture). The emergence of sarcomeric α-actin is verified through immunofluorescence and gene expression. Overall, this work presents an effective and practical tool for the fabrication of pre-vascularized engineered tissues.

Original languageEnglish (US)
Article number2200448
JournalAdvanced Healthcare Materials
Volume11
Issue number24
DOIs
StatePublished - Dec 21 2022
Externally publishedYes

Keywords

  • Kenics static mixer
  • bioprinting
  • multi-channel
  • sacrificial ink
  • vascularization

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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