Bioprinting of Aptamer-Based Programmable Bioinks to Modulate Multiscale Microvascular Morphogenesis in 4D

Deepti Rana, Vincent R. Rangel, Prasanna Padmanaban, Vasileios D. Trikalitis, Ajoy Kandar, Hae Won Kim, Jeroen Rouwkema*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
77 Downloads (Pure)

Abstract

Dynamic growth factor presentation influences how individual endothelial cells assemble into complex vascular networks. Here, programmable bioinks are developed that facilitate dynamic vascular endothelial growth factor (VEGF) presentation to guide vascular morphogenesis within 3D-bioprinted constructs. Aptamer's high affinity is leveraged for rapid VEGF sequestration in spatially confined regions and utilized aptamer-complementary sequence (CS) hybridization to tune VEGF release kinetics temporally, days after bioprinting. It is shown that spatial resolution of programmable bioink, combined with CS-triggered VEGF release, significantly influences the alignment, organization, and morphogenesis of microvascular networks in bioprinted constructs. The presence of aptamer-tethered VEGF and the generation of instantaneous VEGF gradients upon CS-triggering restricted hierarchical network formation to the printed aptamer regions at all spatial resolutions. Network properties improved as the spatial resolution decreased, with low-resolution designs yielding the highest network properties. Specifically, CS-treated low-resolution designs exhibited significant vascular network remodeling, with an increase in vessel density(1.35-fold), branching density(1.54-fold), and average vessel length(2.19-fold) compared to non-treated samples. The results suggest that CS acts as an external trigger capable of inducing time-controlled changes in network organization and alignment on-demand within spatially localized regions of a bioprinted construct. It is envisioned that these programmable bioinks will open new opportunities for bioengineering functional, hierarchically self-organized vascular networks within engineered tissues.

Original languageEnglish
Article number2402302
JournalAdvanced healthcare materials
Volume14
Issue number1
Early online date1 Nov 2024
DOIs
Publication statusPublished - 3 Jan 2025

Keywords

  • UT-Hybrid-D
  • Aptamers
  • Dynamic growth factors presentation
  • Programmable bioinks
  • Tissue engineering
  • Vascular endothelial growth factor
  • Vascularization
  • 3D-bioprinting

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