Development and Characterization of Gelatin‐Norbornene Bioink to Understand the Interplay between Physical Architecture and Micro‐Capillary Formation in Biofabricated Vascularized Constructs (Adv. Healthcare Mater. 2/2022)

Soliman, Bram G.; Major, Gretel; Atienza‐Roca, Pau; Murphy, Caroline A.; Longoni, Alessia; Alcala-Orozco, Cesar R; Rnjak‐Kovacina, Jelena; Gawlitta, Debby; Woodfield, Tim B. F.; Lim, Khoon S.

doi:10.1002/adhm.202270007

Cited by 7 publications

(13 citation statements)

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“…Ru/SPS system is increasingly used in the photocrosslinking of GelMA [68] and GelNB (i.e., Gel-NOR) hydrogels. [69,70] At equivalent gelatin macromer concentration, Ru/SPS-crosslinked GelNB hydrogels were demonstrated to have higher crosslinking efficiency than the GelMA counterparts, as demonstrated by the lower sol fraction and higher compressive modulus of the GelNB hydrogels. [70] In general, while visible light wavelengths (𝜆 ≈ 400 to 700 nm) are arguably safer than UV light wavelengths, visible light-initiated crosslinking is not as fast as longwave UV light, and it may require or produce some cytotoxic species.…”

Section: Visible Light-initiated Thiol-norbornene Photopolymerizationmentioning

confidence: 99%

Orthogonally Crosslinked Gelatin‐Norbornene Hydrogels for Biomedical Applications

Lin,

Frahm,

Afolabi

2023

Macromolecular Bioscience

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The thiol‐norbornene photo‐click reaction has exceptionally fast crosslinking efficiency compared with chain‐growth polymerization at equivalent macromer contents. The orthogonal reactivity between norbornene and thiol/tetrazine permits crosslinking of synthetic and naturally derived macromolecules with modularity, including poly(ethylene glycol) (PEG)‐norbornene (PEGNB), gelatin‐norbornene (GelNB), among others. For example, collagen‐derived gelatin contains both cell adhesive motifs (e.g., Arg‐Gly‐Asp or RGD) and protease‐labile sequences, making it an ideal macromer for forming cell‐laden hydrogels. First reported in 2014, GelNB is increasingly used in orthogonal crosslinking of biomimetic matrices in various applications. GelNB can be crosslinked into hydrogels using multi‐functional thiol linkers (e.g., dithiothreitol (DTT) or PEG‐tetra‐thiol (PEG4SH) via visible light or longwave ultraviolet (UV) light step‐growth thiol‐norbornene reaction or through an enzyme‐mediated crosslinking (i.e., horseradish peroxidase, HRP). GelNB‐based hydrogels can also be modularly crosslinked with tetrazine‐bearing macromers via inverse electron‐demand Diels‐Alder (iEDDA) click reaction. This review surveys the various methods for preparing GelNB macromers, the crosslinking mechanisms of GelNB‐based hydrogels, and their applications in cell and tissue engineering, including crosslinking of dynamic matrices, disease modeling, and tissue regeneration, delivery of therapeutics, as well as bioprinting and biofabrication.

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Section: Visible Light-initiated Thiol-norbornene Photopolymerizationmentioning

confidence: 99%

Orthogonally Crosslinked Gelatin‐Norbornene Hydrogels for Biomedical Applications

Lin,

Frahm,

Afolabi

2023

Macromolecular Bioscience

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“…An alternative cross-linking mechanism to stabilize gelatin is based on the dimerization of thiols with reactive carbon-carbon [178] Copyright 2021, Wiley-VCH GmbH. b) Comparison of cell viability of human umbilical vein endothelial cells (HUVECs) in GelMA versus GelNB/SH.…”

Section: Thiol-ene Click Chemistry In Gelatin Bioinksmentioning

confidence: 99%

mentioning

confidence: 99%

Advances in Gelatin Bioinks to Optimize Bioprinted Cell Functions

Asim

Tabish

Liaqat

et al. 2023

Adv Healthcare Materials

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Gelatin is a widely utilized bioprinting biomaterial due to its cell‐adhesive and enzymatically cleavable properties, which improve cell adhesion and growth. Gelatin is often covalently cross‐linked to stabilize bioprinted structures, yet the covalently cross‐linked matrix is unable to recapitulate the dynamic microenvironment of the natural extracellular matrix (ECM), thereby limiting the functions of bioprinted cells. To some extent, a double network bioink can provide a more ECM‐mimetic, bioprinted niche for cell growth. More recently, gelatin matrices are being designed using reversible cross‐linking methods that can emulate the dynamic mechanical properties of the ECM. This review analyzes the progress in developing gelatin bioink formulations for 3D cell culture, and critically analyzes the bioprinting and cross‐linking techniques, with a focus on strategies to optimize the functions of bioprinted cells. This review discusses new cross‐linking chemistries that recapitulate the viscoelastic, stress‐relaxing microenvironment of the ECM, and enable advanced cell functions, yet are less explored in engineering the gelatin bioink. Finally, this work presents the perspective on the areas of future research and argues that the next generation of gelatin bioinks should be designed by considering cell–matrix interactions, and bioprinted constructs should be validated against currently established 3D cell culture standards to achieve improved therapeutic outcomes.

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“…Increasingly, GelNB has been used in 3D bioprinting space. [8,36,37] For example, Soliman et al used Gel-NOR (same as our GelNB) as a bioink for DLP bioprinting, [38] where the cross-linking was initiated by a ruthenium/sodium persulfate (Ru/SPS) photoinitiating system. While this work presented convincing evidence that DLP-printed GelNB hydrogels support vascular network formation, no postgelation modification of DLP-printed hydrogel was conducted.…”

Section: Formulation Of Gelnb Bioinkmentioning

confidence: 99%

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

Duong

Lin

2023

Macromolecular Bioscience

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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

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Development and Characterization of Gelatin‐Norbornene Bioink to Understand the Interplay between Physical Architecture and Micro‐Capillary Formation in Biofabricated Vascularized Constructs (Adv. Healthcare Mater. 2/2022)

Cited by 7 publications

References 0 publications

Orthogonally Crosslinked Gelatin‐Norbornene Hydrogels for Biomedical Applications

Orthogonally Crosslinked Gelatin‐Norbornene Hydrogels for Biomedical Applications

Advances in Gelatin Bioinks to Optimize Bioprinted Cell Functions

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

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