3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity

• Published in: PloS one 2017-06, Vol.12 (6), p.e0177628-e0177628
• Main Authors: Poldervaart, Michelle T, Goversen, Birgit, de Ruijter, Mylene, Abbadessa, Anna, Melchels, Ferry P W, Öner, F Cumhur, Dhert, Wouter J A, Vermonden, Tina, Alblas, Jacqueline
• Format: Article
• Language: English
• Subjects: 3D printing; Addition polymerization; Biocompatibility; Biodegradability; Biodegradation; Biology and life sciences; Biomedical materials; Bioprinting; Bone biomaterials; Bone marrow; Bone morphogenetic protein 2; Bone morphogenetic proteins; Bone Regeneration; Bones; Cell culture; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured - drug effects; Criteria; Crosslinking; Differentiation; Dynamic mechanical analysis; Elastic limit; Elastic properties; Engineering; Engineering and technology; Extracellular matrix; Gels; Glycosaminoglycans - chemical synthesis; Glycosaminoglycans - chemistry; Glycosaminoglycans - pharmacology; Humans; Hyaluronic acid; Hyaluronic Acid - chemical synthesis; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Hydrogel, Polyethylene Glycol Dimethacrylate - chemical synthesis; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Hydrogels; Irradiation; Light emitting diodes; Mechanical analysis; Mechanical properties; Mesenchymal Stromal Cells - drug effects; Mesenchyme; Mineralization; Modulus of elasticity; Molecular weight; NMR; Nuclear magnetic resonance; Osteogenesis - drug effects; Pharmaceutical sciences; Pharmaceuticals; Physical Sciences; Polymers; Polymethacrylic Acids - chemical synthesis; Polymethacrylic Acids - chemistry; Polymethacrylic Acids - pharmacology; Regenerative medicine; Research and Analysis Methods; Rheology; Rigidity; Skin care products; Stability; Stem cells; Stiffness; Stimuli; Storage; Stromal cells; Surgical implants; Tissue Engineering; Tissue Scaffolds; Ultraviolet radiation; Yield
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0177628

In bone regenerative medicine there is a need for suitable bone substitutes. Hydrogels have excellent biocompatible and biodegradable characteristics, but their visco-elastic properties limit their applicability, especially with respect to 3D bioprinting. In this study, we modified the naturally occurring extracellular matrix glycosaminoglycan hyaluronic acid (HA), in order to yield photo-crosslinkable hydrogels with increased mechanical stiffness and long-term stability, and with minimal decrease in cytocompatibility. Application of these tailor-made methacrylated hyaluronic acid (MeHA) gels for bone tissue engineering and 3D bioprinting was the subject of investigation. Visco-elastic properties of MeHA gels, measured by rheology and dynamic mechanical analysis, showed that irradiation of the hydrogels with UV light led to increased storage moduli and elastic moduli, indicating increasing gel rigidity. Subsequently, human bone marrow derived mesenchymal stromal cells (MSCs) were incorporated into MeHA hydrogels, and cell viability remained 64.4% after 21 days of culture. Osteogenic differentiation of MSCs occurred spontaneously in hydrogels with high concentrations of MeHA polymer, in absence of additional osteogenic stimuli. Addition of bone morphogenetic protein-2 (BMP-2) to the culture medium further increased osteogenic differentiation, as evidenced by increased matrix mineralisation. MeHA hydrogels demonstrated to be suitable for 3D bioprinting, and were printed into porous and anatomically shaped scaffolds. Taken together, photosensitive MeHA-based hydrogels fulfilled our criteria for cellular bioprinted bone constructs within a narrow window of concentration.