Evaluating material-driven regeneration in a tissue engineered human in vitro bone defect model

Wildt, Bregje W. M. de; Cramer, Esther E A; Silva, Leanne S. de; Ito, Keita; Gawlitta, Debby; Hofmann, Sandra

doi:10.1016/j.bone.2022.116597

Cited by 4 publications

(1 citation statement)

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“…Human in vitro bone defect models for biomaterial testing are rarely reported. Only one report has proposed an in vitro model by co-culturing human umbilical vein endothelial cells (HUVECs) with human bone marrow-derived mesenchymal stromal cells (hBM-SCs) on silk fibroin scaffolds with in vitro critically sized defects for 28 d, and then materials were artificially implanted and HUVEC and hBMSC migration, cell-material interactions, and osteoinduction were evaluated 14 d after implantation [12]. Various technologies have been applied for building in vitro threedimensional (3D) tissue models, such as spheroids [13], scaffolds [14][15][16], hydrogels [17], bioreactors [18], microfluidics [19] and cell sheets [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Cell sheet-based in vitro bone defect model for long term evaluation of bone repair materials

Gao,

Li,

et al. 2023

Biomed. Mater.

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Development of tissue-engineered in vitro human bone defect models for evaluation of bone repair materials(BRM) is a promising approach for addressing both translational and ethical concerns regarding animal models. In this study, human bone marrow mesenchymal stem cell (hBMSC) sheets were stacked to form a periosteum like tissue. HE staining showed a cell-dense, multilayered structure. BRMs were implanted in the defect area of the three-dimensional (3D) model. The CCK-8 test demonstrated that the 3D model was stronger in resisting the cytotoxicity of three kinds of commercial BRMs than the 2D culture model, which was consistent with in vivo results. After 28 days implantation in the 3D model, western blot and RT-qPCR showed that three materials induced increased expressions of RUNX2, OSX, OCN , OPN, while Materials B and C seemed to have stronger osteoinductivity than A. In vivo experiments also confirmed the osteoinductivity of the BRMs after 28 and 182 days implantation. Alizarin red staining proved that the mineralized nodules of Materials B and C were more than that of A. The differences of osteogenic properties among three BMRs might be attributed to calcium ion release. This cell sheet-based bone tissue model can resist cytotoxicity of BRMs, demonstrating the priority of long-term evaluation of osteoinductivity of BRMs. Further, the osteoinduction results of the 3D model corresponded to that of in vivo experiments, suggesting this model may have a potential to be used as a novel tool for rapid, accurate evaluation of BRMs, and thus shorten their research and development process.

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