An injectable double-network hydrogel for the co-culture of vascular endothelial cells and bone marrow mesenchymal stem cells for simultaneously enhancing vascularization and osteogenesis

The achievement of rapid vascularization in large implanted constructs is a major challenge in the field of bone tissue engineering. Although co-culture of bone-forming cells and vascular endothelial cells (VECs) has been expected to be a way of promoting vascularization during bone formation with a scaffold, there is a lack of detailed knowledge about the direct interactions between two types of stem cells in a three-dimensional (3D) extracellular matrix (ECM). Herein, we report on the use of an injectable cytocompatible double-network (DN) hydrogel to encapsulate, co-culture and subsequently stimulate the angiogenic/osteogenic differentiation of VECs and the human bone marrow mesenchymal stem cells (BM-MSCs), which demonstrates that the direct co-cultured system enables simultaneous enhancement of vascularization and osteogenesis by providing 3D cell-cell communication. Besides, the improved mechanical properties and the injectability of the DN hydrogel allow the delivery, long-time implantation, proliferation and differentiation of stem cells in vivo. Therefore, this study could provide a niche-like native ECM for stem cell survival and the regulation of the differentiation of multiple cell lines which will benefit bone repair.