Engineering prevascularized composite cell sheet by light-induced cell sheet technology

Abstract

Early vascularization in bone defects has been considered to play a critical role in the bone regeneration process. Although mesenchymal stem cells (MSCs) co-cultured with endothelial cells (ECs) have attracted the most attention in strategies that seek to achieve vascularized bone, it still remains a challenge to achieve a prevascularized construct in vitro that can be translated conveniently. Here, we provided a strategy of engineering a transferable prevascularized MSC-EC composite cell sheet to promote the vascular-like network formation for bone tissue engineering. We co-cultured human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on a distinct light-responsive TiO2 nanodots film. Various cell ratios of MSC-EC and culture mediums were explored to achieve the optimal angiogenesis capacity. The prevascularized MSC-EC composite cell sheet was then detached as an intact and confluent cell layer by a simple light treatment, and showed high viability and 3D network formation surrounded by mesenchymal stem cells. This light-induced cell sheet technology therefore realized a novel transferable prevascularized MSC-EC composite cell sheet, and will have a profound impact on further strategies for designing in-bone tissue engineering.