3D bioprinting of high-performance hydrogel with in-situ birth of stem cell spheroids
Shunyao Zhu, Xueyuan Liao, Yue Xu, Nazi Zhou, Yingzi Pan, Jinlin Song, Taijing Zheng, Lin Zhang, Liyun Bai, Yu Wang, Xia Zhou, Maling Gou, Jie Tao, Rui Liu
Abstract
Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo . The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications. • A strategy for the 3D bioprinting of high-performance hydrogel is introduced. • The designed hydrogels simulate MSC spheroid growth and stemness maintenance. • The hydrogels support the regeneration of dentin and neovascular-like structures.