VA‐086 methacrylate gelatine photopolymerizable hydrogels: A parametric study for highly biocompatible 3<scp>D</scp> cell embedding

Occhetta, Paola; Visone, Roberta; Russo, Laura; Cipolla, Laura; Moretti, Matteo; Rasponi, Marco

doi:10.1002/jbm.a.35346

Cited by 105 publications

(74 citation statements)

References 32 publications

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“…Photocrosslinking via UV light (250 nm < λ < 400 nm) relies on the use of photoinitiators such as Irgacure 2959 26, 27 . However, alternative photoinitiators such as VA-086, that absorb safer UV ranges (≈405 nm) than Irgacure 2959 and lead to enhanced cytocompatibility have been recently described 33 . UV light photons cause dissociation of the photoinitiator into two radicals, which cause radical formation on the methacryloyl groups.…”

Section: Resultsmentioning

confidence: 99%

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels

et al. 2017

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Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although, ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5–56 kPa, by changing the concentrations of the co-initiator and co-monomer in the precursor formulation. In addition, the average pore sizes (26–103 μm) and swelling ratio (7–13%) were also shown to be tunable by varying the hydrogel formulation. In vitro studies showed that visible light crosslinked GelMA hydrogels supported the growth and function of primary cardiomyocytes (CMs). In addition, the engineered materials were shown to be biocompatible in vivo, and could be successfully delivered to the heart after myocardial infarction in an animal model to promote tissue healing. The developed visible light crosslinked hydrogel could be used for the repair of various soft tissues such as the myocardium, and for the treatment of cardiovascular diseases with enhanced therapeutic functionality.

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Section: Resultsmentioning

confidence: 99%

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels

et al. 2017

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“…However, there are concerns related to the cytotoxicity of the free radicals generated using I2959 for fast dividing cell lines . Therefore, in search for a more viable photoinitiator, previous studies using alginate and gelatin‐based hydrogels have demonstrated that a water‐soluble Azo initiator 2,2′‐azobis[2‐methyl‐ N ‐(2‐hydroxyethyl)propionamide] (VA086) is more cytocompatible and hence can serve as a promising alternative to I2959 for photochemical crosslinking of natural hydrogels …”

Section: Introductionmentioning

confidence: 99%

“…12,13 Therefore, in search for a more viable photoinitiator, previous studies using alginate and gelatin-based hydrogels have demonstrated that a water-soluble Azo initiator 2,2 0 -azobis [2-methyl-N-(2-hydroxyethyl)propionamide] (VA086) is more cytocompatible and hence can serve as a promising alternative to I2959 for photochemical crosslinking of natural hydrogels. [14][15][16][17][18][19] Collagen scaffolds are commonly used for tissue engineering applications [20][21][22] because of their resemblance to the biological properties of most native tissues. While gelatin and collagen have identical amino acid sequences, the secondary structure of these proteins is different and gelatin scaffolds are weaker than collagen scaffolds.…”

Section: Introductionmentioning

confidence: 99%

Photochemically crosslinked cell‐laden methacrylated collagen hydrogels with high cell viability and functionality

Nguyen

Watkins

Kishore

2019

J Biomedical Materials Res

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Irgacure 2959 (I2959) is widely used as a photoinitiator for photochemical crosslinking of hydrogels. However, the free radicals generated from I2959 have been reported to be highly cytotoxic. In this study, methacrylated collagen (CMA) hydrogels were photochemically crosslinked using two different photoinitiators (i.e., I2959 and VA086) and the effect of photoinitiator type, photoinitiator concentration (i.e., 0.02 and 0.1%) and crosslinking time (1 and 10 min) on gel morphology, compressive modulus, and stability were investigated. In addition, Saos‐2 cells were encapsulated within the hydrogels and the effect of photochemical crosslinking conditions on cell viability, metabolic activity, and osteoblast functionality was assessed. Scanning electron microscopy imaging showed that photochemical crosslinking decreased the porosity of the hydrogels resulting in decrease in water retention ability compared to uncrosslinked hydrogels. On the other hand, photochemical crosslinking improved the stability of CMA hydrogels (p < 0.05). Uniaxial compression tests showed that increasing the photoinitiator concentration significantly improved the compressive modulus of CMA hydrogels (p < 0.05). Results from the live–dead assay showed that VA086 crosslinked hydrogels exhibited higher cell viability compared to I2959 (p < 0.05) crosslinked hydrogels indicating that VA086 is more cytocompatible compared to I2959. Furthermore, Alizarin Red S staining revealed a significantly more pronounced cell‐mediated mineralization on VA086 crosslinked hydrogels (p < 0.05) indicating that Saos‐2 cells retain their normal functionality in the presence of VA086. In summary, these results indicate that VA086 is a more biocompatible photoinitiator compared to I2959 for the generation of photochemically crosslinked CMA hydrogels for tissue engineering applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

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“…In this study, we exploited chemically modified gelatin (gel‐MOD) with methacrylate groups that can be cross‐linked with UV irradiation in the presence of a photoinitiator (Van Den Bulcke et al, ), as an encapsulation material for valvular microtissues. Two different w / v % gel‐MOD hydrogels were generated and cross‐linked in the presence of the photoinitiator Irgacure 2959 (Irg), which is considered as the golden standard for gel‐MOD cross‐linking, or VA‐086 (VA), which has been shown to be a more cytocompatible photoinitiator (Billiet et al, ; Occhetta et al, ; Rouillard et al, ). Physical and biomechanical analysis was performed to analyze hydrogel properties (gel fraction, swelling ratio, and stiffness).…”

Section: Introductionmentioning

confidence: 99%

Impact of modified gelatin on valvular microtissues

Roosens

Handoyo

Dubruel

et al. 2019

J Tissue Eng Regen Med

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A significant challenge in the field of tissue engineering is the biofabrication of three‐dimensional (3D) functional tissues with direct applications in organ‐on‐a‐chip systems and future organ engineering. Multicellular valvular microtissues can be used as building blocks for the formation of larger scale valvular macrotissues. Yet, for the controlled biofabrication of 3D macrotissues with predefined complex shapes, directed assembly of microtissues through bioprinting is needed. This study aimed to investigate if modified gelatin is an instructive material for valvular microtissues. Valvular microtissues were encapsulated in modified gelatin hydrogels and cross‐linked in the presence of a photoinitiator (Irgacure 2959 or VA‐086). Hydrogel properties were determined, and valvular interstitial cell functions like phenotype, proliferation, migration, mRNA expression of extracellular matrix (ECM) molecules, ECM deposition, and tissue fusion were characterized by histochemical stainings and RT‐qPCR. Encapsulated microtissues remained viable, produced heart valve‐related ECM components, and remained in a quiescent state. However, encapsulation induced some changes in ECM formation and gene expression. Encapsulated microtissues showed lower remodeling capacity and increased expression levels of Col I/V, elastin, hyaluronan, biglycan, decorin, and Sox9 compared with nonencapsulated microtissues. Furthermore, this study demonstrated that proliferation, migration, and tissue fusion was more pronounced in softer gels. In general, we evidenced that modified gelatin is an instructive material for physiologically relevant valvular microtissues and provided a proof of concept for the formation of larger valvular tissue by assembling microtissues at random in soft gels.

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VA‐086 methacrylate gelatine photopolymerizable hydrogels: A parametric study for highly biocompatible 3D cell embedding

Cited by 105 publications

References 32 publications

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels

Photochemically crosslinked cell‐laden methacrylated collagen hydrogels with high cell viability and functionality

Impact of modified gelatin on valvular microtissues

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