Biofabrication of skin tissue constructs using alginate, gelatin and diethylaminoethyl cellulose bioink

Int J Biol Macromol. 2021 Oct 31:189:398-409. doi: 10.1016/j.ijbiomac.2021.08.114. Epub 2021 Aug 20.

Abstract

Introduction: Biofabrication of skin tissue equivalents using 3D bioprinting technology has gained much attention in recent times due to the simplicity, the versatility of the technology and its ability in bioengineering biomimetic tissue histology. The key component being the bioink, several groups are actively working on the development of various bioink formulations for optimal skin tissue construction.

Methods: Here, we present alginate (ALG), gelatin (GEL) and diethylaminoethyl cellulose (DCEL) based bioink formulation and its application in bioprinting and biofabrication of skin tissue equivalents. Briefly, DEAE cellulose powder was dispersed in alginate solution with constant stirring at 60 °C to obtain a uniform distribution of cellulose fibers; this was then mixed with GEL solution to prepare the bioink. The formulation was systematically characterized for its morphological, physical, chemical, rheological, biodegradation and biocompatibility properties. The printability, shape fidelity and cell-laden printing were assessed using the CellInk bioprinter.

Results: The bioink proved to be a good printable, non-cytotoxic and stable hydrogel formulation. The primary human fibroblast and keratinocyte-loaded 3D bioprinted constructs showed excellent cell viability, collagen synthesis, skin-specific marker and biomimetic tissue histology.

Conclusion: The results demonstrated the successful formulation of ALG-GEL-DCEL bioink and its application in the development of human skin tissue equivalents with distinct epidermal-dermal histological features.

Keywords: Cocultures; Hydrogels; Printability; Tissue engineering; Tissue equivalents; Wound healing.

MeSH terms

  • Adult
  • Alginates / pharmacology*
  • Animals
  • Biocompatible Materials / chemistry
  • Biomarkers / metabolism
  • Bioprinting
  • Cell Line
  • DEAE-Cellulose / chemistry*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Gelatin / pharmacology*
  • Hemolysis / drug effects
  • Humans
  • Ink*
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Mice
  • Microtechnology*
  • Printing, Three-Dimensional
  • Rheology
  • Skin / drug effects*
  • Skin, Artificial
  • Spectroscopy, Fourier Transform Infrared
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry*

Substances

  • Alginates
  • Biocompatible Materials
  • Biomarkers
  • Gelatin
  • DEAE-Cellulose