Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed.

Cryogel based scaffolds have high porosity with interconnected macropores that may provide cell compatible microenvironment. In addition, cryogel based scaffolds can be utilized in minimally invasive surgery due to its sponge-like properties, including rapid shape recovery and injectability. Herein, we developed an injectable cryogel by conjugating heparin to gelatin as a carrier for vascular endothelial growth factor (VEGF) and fibroblasts in hindlimb ischemic disease. Our gelatin/heparin cryogel showed gelatin concentration-dependent mechanical properties, swelling ratios, interconnected porosities, and elasticities. In addition, controlled release of VEGF led to effective angiogenic responses both in vitro and in vivo. Furthermore, its sponge-like properties enabled cryogels to be applied as an injectable carrier system for in vivo cells and growth factor delivery. Our heparin functionalized injectable cryogel facilitated the angiogenic potential by facilitating neovascularization in a hindlimb ischemia model.

BackgroundTissue engineering is an interdisciplinary field that attempts to restore or regenerate tissues and organs through biomimetic fabrication of scaffolds with specific functionality. In recent years, graphene oxide (GO) is considered as promising biomaterial due to its nontoxicity, high dispersity, and hydrophilic interaction, and these characteristics are key to stimulating the interactions between substrates and cells.MethodIn this study, GO substrates were fabricated via chemically immobilizing GO at 1.0 mg/ml on glass slides. Furthermore, we examined the osteogenic responses of murine mesenchymal-like stem cells, C3H10T1/2 cells, on GO substrates.ResultsC3H10T1/2 cells on GO substrates resulted in increased cell surface area, enhanced cellular adhesions, and instigated osteogenic differentiation. Furthermore, priming of C3H10T1/2 cells with chondrocyte-conditioned medium (CM) could further induce a synergistic effect of osteogenesis on GO substrates.ConclusionsAll of these data suggest that GO substrate along with CM is suitable for upregulating osteogenic responses of mesenchymal stem cells.

Chondroitin sulfate (CS) is the major component of glycosaminoglycan in connective tissue. In this study, we fabricated methacrylated PEGDA/CS-based hydrogels with varying CS concentration (0, 1, 5, and 10%) and investigated them as biomineralizing three-dimensional scaffolds for charged ion binding and depositions. Due to its negative charge from the sulfate group, CS exhibited an osteogenically favorable microenvironment by binding charged ions such as calcium and phosphate. Particularly, ion binding and distribution within negatively charged hydrogel was dependent on CS concentration. Furthermore, CS dependent biomineralizing microenvironment induced osteogenic differentiation of human tonsil-derived mesenchymal stem cells in vitro. Finally, when we transplanted PEGDA/CS-based hydrogel into a critical sized cranial defect model for 8 weeks, 10% CS hydrogel induced effective bone formation with highest bone mineral density. This PEGDA/CS-based biomineralizing hydrogel platform can be utilized for in situ bone formation in addition to being an investigational tool for in vivo bone mineralization and resorption mechanisms.

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