Abstract
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.
Highlights
Natural hydrogels are increasingly applied in regenerative medicine, as they can provide scaffolds with unique biocompatible and biodegradable properties [1]
Polymer batches with a DS between 5 and 7% were selected for further experiments, since these yielded hydrogels with visco-elastic properties that allow handling with a pipette, a necessity for the experiments that involve cell-incorporation, moulding and 3D bioprinting (Fig 1B)
Effectivity of UV-induced methacrylated hyaluronic acid (MeHA) crosslinking over time was assessed by rheometry
Summary
Natural hydrogels are increasingly applied in regenerative medicine, as they can provide scaffolds with unique biocompatible and biodegradable properties [1]. Properties, hydrogels can be employed as cell-friendly materials that can present signals to guide cellular processes and release proteins or drugs in a controlled fashion [4]. This makes hydrogel scaffolds very suitable for tissue engineering purposes, the reason why worldwide research is increasingly focusing on the manufacturing and optimization of hydrogels [5,6,7]. 3D bioprinting offers the advantage of creating porous constructs with predefined complex architecture, allowing deposition of specific cell types, signaling molecules or biomaterials at predefined regions [12] This technique allows better mimicry of native tissue organization compared to the other deposition methods mentioned above, for example by addition of specific and predefined vasculature stimulating regions to a bone promoting scaffold
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