Automated and Enclosed Three-Dimensional Biofabrication System for Mesenchymal Stem Cell Culture to Enhance Diabetic Wound Healing

作者：Yanmei Chen, Yang Xu, Jiawei Cai, Marianne Lauwers, Xiang Li, Yali Zheng, Hua Chu, Xiang‐Long Chen, Dai Fei Elmer Ker, Cheng Zhang, Dan Wang, Zhiyong Zhang · 发表于：Biomaterials Research · 年份：2025 · DOI：10.34133/bmr.0205 · 被引用次数：5 · 研究领域：Mesenchymal stem cell research、3D Printing in Biomedical Research、Electrospun Nanofibers in Biomedical Applications

The industrialization of mesenchymal stem cells for regenerative medicine faces substantial challenges, particularly in large-scale production. Conventional 2-dimensional (2D) culture systems demonstrate limitations in meeting clinical requirements, such as inadequate cell yield, and poor cell-cell and cell-matrix interactions. These challenges can potentially be addressed by employing a 3D culture platform, which offers higher cell yields and enhanced efficacy. Moreover, it is essential to conduct a systematic and rigorous evaluation of cells produced in 3D culture systems to ensure their successful clinical translation. In this study, we cultured human umbilical cord mesenchymal stem cells (hUCMSCs) using an automated, scalable, and enclosed 3D microcarrier-bioreactor system, and comprehensively investigated their biological characteristics and potential therapeutic effects for diabetic wound repair. Our findings revealed that hUCMSCs harvested from this 3D microcarrier-bioreactor system are genetically stable and maintain the trilineage differentiation potential. Compared to hUCMSCs expanded under 2D conditions, those cultured in 3D exhibited reduced senescence and enhanced capabilities in migration, angiogenesis, and anti-inflammatory responses across different passages in vitro. RNA-sequencing analysis showed higher expression levels of genes related to angiogenesis and anti-inflammatory pathways in hUCMSCs cultured in 3D compared to those in 2D, which was further valida...