Digital Light Processing 3D Bioprinting of Gelatin‐Norbornene Hydrogel for Enhanced Vascularization

Abstract

Digital light processing (DLP) bioprinting can be used to fabricate volumetric scaffolds with intricate internal structures, such as perfusable vascular channels. The successful implementation of DLP bioprinting in tissue fabrication requires using suitable photo‐reactive bioinks. Norbornene‐based bioinks have emerged as an attractive alternative to (meth)acrylated macromers in 3D bioprinting owing to their mild and rapid reaction kinetics, high cytocompatibility for in situ cell encapsulation, and adaptability for post‐printing modification or conjugation of bioactive motifs. In this contribution, we report the development of gelatin‐norbornene (GelNB) as a photocrosslinkable bioink for DLP 3D bioprinting. Low concentrations of GelNB (2‐5 wt%) and poly(ethylene glycol)‐tetra‐thiol (PEG4SH) were DLP‐printed with a wide range of stiffness (G' ∼120 to 4,000 Pa) and with perfusable channels. DLP‐printed GelNB hydrogels were highly cytocompatible, as demonstrated by the high viability of the encapsulated human umbilical vein endothelial cells (HUVECs). The encapsulated HUVECs formed an interconnected microvascular network with lumen structures. Notably, the GelNB bioink permitted both in situ tethering and secondary conjugation of QK peptide, a vascular endothelial growth factor (VEGF)‐mimetic peptide. Incorporation of QK peptide significantly improved endothelialization and vasculogenesis of the DLP‐printed GelNB hydrogels, reinforcing the applicability of this bioink system in diverse biofabrication applications.This article is protected by copyright. All rights reserved

Orthogonally Crosslinked Gelatin‐Norbornene Hydrogels for Biomedical Applications

“…[69] Our group has also used DLP bioprinting to print GelNB hydrogels for the purpose of enhancing vascularization. [119] In addition to demonstrating the cytocompatibility of DLP-printed GelNB hydrogels for in situ encapsulation and vascularization of human umbilical vein endothelial cells (HUVECs), we showed that the encapsulated HUVECs formed microvascular networks with lumen structures. Furthermore, the GelNB bioink permitted both in situ conjugation and secondary photo-tethering of pro-angiogenic and pro-vasculogenic QK peptide, a biomimetic peptide derived from vascular endothelial growth factor (VEGF).…”

Applications, advancements, and challenges of 3D bioprinting in organ transplantation

“…Van Thuy Duong et al reported that they applied the thiol-norbornene cross-linked GelNB hydrogel designed and synthesized by them for encapsulating cells for vascular formation. 47 The special hydrogel has several advantages such as lower initial stiffness ( G ′ ∼ 100–4000 Pa) for better cell viability, physiological status perfusable channels and conjugation of various angiogenic peptides to improve vascularization.…”