Radical scavenging gelatin methacrylamide based bioink formulation for three dimensional bioprinting of parenchymal liver construct

Pai, Roopesh R.; Ajit, Shilpa; J, Anupama Sekar; Nair, Sreekumaran; Pr, Anil Kumar; Velayudhan, Shiny

doi:10.1016/j.bprint.2022.e00214

Cited by 3 publications

(7 citation statements)

References 43 publications

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“…GelMA which forms covalently cross-linked hydrogels under UV light (λ = 365 nm) exposure in the presence of a photoinitiator, is a widely used hydrogel in bioink formulations for 3D bioprinting. GelMA bioink has been studied for the fabrication of cardiac, skeletal, neural, bone, cartilage, and skin tissues because of its excellent flow properties, biocompatibility, and controllable biodegradability [10,15]. After 3D bioprinting, the cell-laden constructs were exposed to ultraviolet (UV) light.…”

Section: Discussionmentioning

confidence: 99%

“…GelMA was synthesized and characterized as previously reported [10,14]. Gelatin was modified by reacting with methacrylic anhydride under optimum temperature and pH.…”

Section: Synthesis Of Gelmamentioning

confidence: 99%

“…Two antioxidant vitamins, AA and α-Toc were used. The concentration of AA selected was 3.4 mM as previously reported [10]. The concentrations of α-Toc were 25 µM and 100 µM.…”

Section: Photoprotective Analysis Of Antioxidant Cocktail Loaded Gelmamentioning

confidence: 99%

“…The photoprotective GelMA was formulated by optimizing the concentration of antioxidants and their subsequent effect on iROS production within encapsulated HepG2 cells. We have previously reported the standardized concentration of cytoplasmic protective agents by incorporating 3.4 mM AA into GelMA [10]. The effect of free radicals on the cell membrane may also affect cells.…”

Section: Photoprotective Effect Of Antioxidant Loaded Gelma On Cellsmentioning

confidence: 99%

“…GelMA is readily photocrosslinkable in presence of photoinitiators like Irgacure 2959 and Lithium phenyl-2,4,6trimethylbenzoylphosphinate [9]. We have reported previously that during photo-crosslinking of GelMA, excess reactive oxygen species (ROSs) are generated within HepG2 cells embedded in GelMA and inclusion of a free radical scavenger (FRS) molecule, such as AA (vitamin C) in the GelMA bioink could nullify the adverse effect of excess ROS produced inside the cells [10]. The use of antioxidants as photoprotectants, either alone or in combination, has been extensively documented in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Biocompatibility evaluation of antioxidant cocktail loaded gelatin methacrylamide as bioink for extrusion-based 3D bioprinting

Velayudhan

2023

Biomed. Mater.

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Three-dimensional (3D) liver bioprinting is a promising technique for creating 3D liver models that can be used for in vitro drug testing, hepatotoxicity studies, and transplantation. The functional performance of 3D bioprinted liver constructs are limited by the lack of cell-cell interactions, which calls for the creation of bioprinted tissue constructs with high cell densities. This study reports the fabrication of 3D bioprinted liver constructs using a novel photocrosslinkable Gelatin Methacrylamide (GelMA)-based bioink formulation. However, the formation of excess free radicals during photoinitiation poses a challenge, particularly during photocrosslinking of large constructs with high cell densities. Hence, we designed a bioink formulation comprising the base polymer GelMA loaded with an antioxidant cocktail containing vitamin C (L-ascorbic acid) and vitamin E (α-tocopherol). We confirmed that the combination of antioxidants loaded in GelMA enhanced the ability to scavenge intracellular Reactive Oxygen Species (iROS) formed during photocrosslinking. The GelMA formulation was evaluated for biocompatibility in vitro and in vivo. These results demonstrated that the bioink had adequate rheological characteristics and was biocompatible. Furthermore, constructs with high-density primary rat hepatocytes were 3D bioprinted and showed improved cell-cell interactions and liver specific functions such as albumin and urea secretion were increased 5-fold and 2.5-fold respectively when compared with bioprinted constructs with lower cell concentrations.

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Section: Discussionmentioning

confidence: 99%

“…GelMA was synthesized and characterized as previously reported [10,14]. Gelatin was modified by reacting with methacrylic anhydride under optimum temperature and pH.…”

Section: Synthesis Of Gelmamentioning

confidence: 99%

“…Two antioxidant vitamins, AA and α-Toc were used. The concentration of AA selected was 3.4 mM as previously reported [10]. The concentrations of α-Toc were 25 µM and 100 µM.…”

Section: Photoprotective Analysis Of Antioxidant Cocktail Loaded Gelmamentioning

confidence: 99%

Section: Photoprotective Effect Of Antioxidant Loaded Gelma On Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biocompatibility evaluation of antioxidant cocktail loaded gelatin methacrylamide as bioink for extrusion-based 3D bioprinting

Velayudhan

2023

Biomed. Mater.

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In-situ ionic crosslinking of 3D bioprinted cell-hydrogel constructs for mechanical reinforcement and improved cell growth

Lee

Heo

Kim

et al. 2023

Biomaterials Advances

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Silymarin enriched gelatin methacrylamide bioink imparts hepatoprotectivity to 3D bioprinted liver construct against carbon tetrachloride induced toxicity

Anupama Sekar,

Velayudhan,

Senthilkumar

et al. 2024

European Journal of Pharmaceutics and Biopharmaceutics

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Radical scavenging gelatin methacrylamide based bioink formulation for three dimensional bioprinting of parenchymal liver construct

Cited by 3 publications

References 43 publications

Biocompatibility evaluation of antioxidant cocktail loaded gelatin methacrylamide as bioink for extrusion-based 3D bioprinting

Biocompatibility evaluation of antioxidant cocktail loaded gelatin methacrylamide as bioink for extrusion-based 3D bioprinting

In-situ ionic crosslinking of 3D bioprinted cell-hydrogel constructs for mechanical reinforcement and improved cell growth

Silymarin enriched gelatin methacrylamide bioink imparts hepatoprotectivity to 3D bioprinted liver construct against carbon tetrachloride induced toxicity

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