Low-Concentration Gelatin Methacryloyl Hydrogel with Tunable 3D Extrusion Printability and Cytocompatibility: Exploring Quantitative Process Science and Biophysical Properties

Abstract

Three-dimensional (3D) bioprinting of hydrogels with a wide spectrum of compositions has been widely investigated. Despite such efforts, a comprehensive understanding of the correlation among the process science, buildability, and biophysical properties of the hydrogels for a targeted clinical application has not been developed in the scientific community. In particular, the quantitative analysis across the entire developmental path for 3D extrusion bioprinting of such scaffolds is not widely reported. In the present work, we addressed this gap by using widely investigated biomaterials, such as gelatin methacryloyl (GelMA), as a model system. Using extensive experiments and quantitative analysis, we analyzed how the individual components of methacrylated carboxymethyl cellulose (mCMC), needle-shaped nanohydroxyapatite (nHAp), and poly(ethylene glycol)diacrylate (PEGDA) with GelMA as baseline matrix of the multifunctional bioink can influence the biophysical properties, printability, and cellular functionality. The complex interplay among the biomaterial ink formulations, viscoelastic properties, and printability toward the large structure buildability (structurally stable cube scaffolds with 15 mm edge) has been explored. Intriguingly, the incorporation of PEGDA into the GelMA/mCMC matrix offered improved compressive modulus (∼40-fold), reduced swelling ratio (∼2-fold), and degradation rates (∼30-fold) compared to pristine GelMA. The correlation among microstructural pore architecture, biophysical properties, and cytocompatibility is also established for the biomaterial inks. These photopolymerizable bio(material)inks served as the platform for the growth and development of bone and cartilage matrix when human mesenchymal stem cells (hMSCs) are either seeded on two-dimensional (2D) substrates or encapsulated on 3D scaffolds. Taken together, this present study unequivocally establishes a significant step forward in the development of a broad spectrum of shape-fidelity compliant bioink for the 3D bioprinting of multifunctional scaffolds and emphasizes the need for invoking more quantitative analysis in establishing process-microstructure−property correlation.

Gelatin Methacryloyl (GelMA) - 45S5 Bioactive Glass (BG) Composites for Bone Tissue Engineering: 3D Extrusion Printability and Cytocompatibility Assessment Using Human Osteoblasts

“…This is because the 45S5 BG used is of micron-scale being susceptible to precipitation during the preparation process, which leads to a decrease in the mechanical properties due to possible particle agglomeration. Also, Das and Basu utilized nanoscale HA as an inorganic filler to obtain a mechanically superior composite hydrogel. , Song et al also reported the use of HA as an inorganic filler to obtain a porous composite hydrogel of GelMA/HA, but with better mechanical properties than GelMA. Zheng et al provided more insight into the decrease in compressive modulus of hydrogels with the addition of 45S5 BG particles.…”

“…The synthesis process of GelMA was based on a method reported in the literature . Briefly, 10 w/v % GEL was dissolved in 100 mL of DPBS at 60 °C under continuous stirring until fully dissolved.…”