3D printable hyaluronic acid-based hydrogel for its potential application as a bioink in tissue engineering

Abstract

BackgroundAfter recognition of 3D printing and injectable hydrogel as a critical issue in tissue/organ engineering and regenerative medicine society, many hydrogels as bioinks have been developed worldwide by using polymeric biomaterials such as gelatin, alginate, hyaluronic acid and others. Even though some gels have shown good performances in 3D bioprinting, still their performances do not meet the requirements enough to be used as a bioink in tissue engineering.MethodIn this study, a hydrogel consisting of three biocompatible biomaterials such as hyaluronic acid (HA), hydroxyethyl acrylate (HEA) and gelatin-methacryloyl, i.e. HA-g-pHEA-gelatin gel, has been evaluated for its possibility as a bioprinting gel, a bioink. Hydrogel synthesis was obtained by graft polymerization of HEA to HA and then grafting of gelatin- methacryloyl via radical polymerization mechanism. Physical and biological properties of the HA-based hydrogels fabricated with different concentrations of methacrylic anhydride (6 and 8%) for gelatin-methacryloylation have been evaluated such as swelling, rheology, morphology, cell compatibility, and delivery of small molecular dimethyloxalylglycine. Printings of HA-g-pHEA-Gelatin gel and its bioink with bone cell loaded in lattice forms were also evaluated by using home-built multi-material (3D bio-) printing system.ConclusionThe experimental results demonstrated that the HA-g-pHEA-gelatin hydrogel showed both stable rheology properties and excellent biocompatibility, and the gel showed printability in good shape. The bone cells in bioinks of the lattice-printed scaffolds were viable. This study showed HA-g-pHEA-Gelatin gel’s potential as a bioink or its tissue engineering applications in injectable and 3D bioprinting forms.

Hyaluronic acid as a bioactive component for bone tissue regeneration: Fabrication, modification, properties, and biological functions

“…Currently, several studies have used HA or HA derivatives as bioinks for the fabrication of tissue-engineered bone constructs. Noh et al synthesized a hybrid hydrogel from HA, hydroxyethyl acrylate (HEA), and gelatin-methacryloyl and used it as a cell-laden bioink for bone regeneration [109]. The results demonstrated that the hybrid hydrogel showed excellent biocompatibility and good printability (Figure 7a).…”

Bioprinting a cell‐laden matrix for bone regeneration: A focused review

“…Both natural and synthetic polymers are applicable in preparing hydrogelsbased bio-inks. [86][87][88] Although synthetic polymers, including pluronic 89 and PEG, 66 have shown an impressive mechanical strength, often natural polymers, that is, collagen, fibrin, 90 hyaluronic acid, 91 alginate, 92 chitosan, 93 and so forth, are preferred due to the inherent bioactivity or better simulation of natural ECM. 94,95 Also, some of the natural polymers with signaling molecules can promote cellular processes while the living organism-derived polymers are not suitable in cellular interactions.…”

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…For extrusion based printing, hyaluronic acid has been grafted with hydroxyethyl acetate and gelatin-methacrylate to form a hydrogel which was 3D printed into a scaffold with~500 µm resolution [210]. One way to tune mechanical robustness and macro-porosity beyond that of hydrogels is to formulate hyaluronic acid cryogels (hydrogels produced through controlled freezing and thawing of a polymer solution), which have also been 3D printed [211].…”

“…Hyaluronic acid and modified hyaluronic acid show good cyto-and bio-compatibility [207,210], as it is naturally a part of the extra-cellular matrix. Extruded hyaluronic acid structures show excellent bioactivity, with hyaluronic acid based hydrogel scaffolds for improving cell viability [208], promotion of stromal cell elongation with applications in building liver models for drug screening [209], retinal cells culturing [216], immobilization of peptides for mesenchymal stem cell culturing with high angiogenic and osteogenic activity [217], deposition of regenerative scaffolds directly during surgery [218], and supporting human adipose progenitor cell and stromal cell adhesion and proliferation [211].…”

“…Hyaluronic acid (4.3.1) [207][208][209]; Inclusion of GelMA, feature size 500 µm [210]; Cryogel E: 2-2.5 kPa [211]; Post-curing via UV, E: 1.3-10.6 kPa [213] Feature size 300 µm (SLA) [214]; Compressive E: 780 kPa [215] Cartilage tissue engineering and human adipose stem cells [215]; stromal cell elongation and drug screening [209]; retinal cell culturing [216]; hMSCs [217]; human adipose progenitor and stromal cells [211]; Schwann cells [219] Chitosan (4.3.2) [222,223]; Feature size 50 µm [224] [225,226]; Feature size 50 µm (SLA), E: 160-680 kPa [173]; Feature size 400 nm (TPP) [228]; Inclusion of HA [229] Anti-bacterial [230,231]; wound dressings [232]; skin tissue engineering [231]; bone tissue engineering [229]; pluripotent stem cells for neural tissue engineering [233]; articular cartilage tissue engineering [234]; skin constructs [235] Alginate (4.3.3)…”