Gelatin Methacryloyl-Riboflavin (GelMA-RF) Hydrogels for Bone Regeneration.

Ryoma Goto,Takeshi Kikuchi,Eisaku Nishida,Jun-Ichiro Hayashi,Masaki Asakura,Tasuku Ohno,Akio Mitani,Shuichiro Kobayashi,Makoto Aino,Yuki Iwamura,Genta Yamamoto

doi:10.3390/ijms22041635

Ryoma Goto, Takeshi Kikuchi + Show 9 more

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https://doi.org/10.3390/ijms22041635

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Abstract

Gelatin methacryloyl (GelMA) is a versatile biomaterial that has been used in various biomedical fields. UV light is commonly used to photocrosslink such materials; however, its use has raised several biosafety concerns. We investigated the mechanical and biological properties of a visible-wavelength (VW)-light-crosslinked gelatin-based hydrogel to evaluate its viability as a scaffold for bone regeneration in bone-destructive disease treatment. Irgacure2959 or riboflavin was added as a photoinitiator to create GelMA solutions. GelMA solutions were poured into a mold and exposed to either UV or VW light. KUSA-A1 cell-laden GelMA hydrogels were crosslinked and then cultured. Mechanical characterization revealed that the stiffness range of GelMA–RF hydrogel was suitable for osteoblast differentiation. KUSA-A1 cells encapsulated in GelMA hydrogels photopolymerized with VW light displayed significantly higher cell viability than cells encapsulated in hydrogels photopolymerized with UV light. We also show that the expression of osteogenesis-related genes at a late stage of osteoblast differentiation in osteoblasts encapsulated in GelMA–RF hydrogel was markedly increased under osteoblast differentiation-inducing conditions. The GelMA–RF hydrogel served as an excellent scaffold for the encapsulation of osteoblasts. GelMA–RF hydrogel-encapsulated osteoblasts have the potential not only to help regenerate bone mass but also to treat complex bone defects associated with bone-destructive diseases such as periodontitis.

Highlights

The three key elements of tissue engineering are cells, growth factors, and scaffolds [1]
A 20% Gelatin methacryloyl (GelMA)–RF hydrogel disc irradiated for 60 s was colorless and completely transparent, while a similar disc irradiated for 20 s was translucent yellow, which indicated that unpolymerized RF remained
10% and 15% (w/v) GelMA–RF hydrogels were difficult to remove from the mold because of unpolymerized RF and could not be analyzed for their mechanical properties

Summary

Introduction

The three key elements of tissue engineering are cells, growth factors, and scaffolds [1]. Tissue engineering involves growing cells in an appropriate three-dimensional (3D) environment, known as a scaffold, to which the cells attach and colonize. The major function of a scaffold is to replicate the structure of the natural extracellular matrix that assists the proliferation, differentiation, and biosynthesis of cells. Hydrogels have been widely applied for biomedical purposes—including as scaffolds for regenerative medicine and as carriers for drug delivery—owing to their crosslinked network structure and have been modified in various ways to mimic the native extracellular matrix environment. Gelatin methacryloyl (GelMA), a photocrosslinkable material, is a useful, low-cost, and safe scaffold for tissue engineering and has been reported to promote cell proliferation, migration, and spreading in 3D environments [3]. The GelMA solution can form hydrogels that are irreversibly covalently crosslinked through exposure to ultraviolet (UV) light in the presence of a photoinitiator [3]

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