New Vascularization Strategy for large-scale tissue engineering scaffolds

Recently, Professor WU Linping at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, and co-researchers published an article in Advanced Healthcare Materials titled “Microscopically Adaptable Bioink Guide Cell Compartmentalization toward Morphogenesis of a Functional Vasculature-Like System”. In this article, functional engineered vasculatures were developed by a one-step bioprinting strategy.

The dramatically increasing ageing population raises the need for replacing damaged or failing organs. Tissue engineering aiming to create tissues or cellular products may pave a new avenue for supplying organ substitutes. However, prevascularization is the key challenge for large-scale tissue engineering.

The research team developed engineered functional vasculatures and vascularized skin through cell compartmentalization in an extracellular matrix (ECM)-mimicking bioink. The ECM-mimicking bioink was designed with interpenetrated orthogonal dynamic-covalent crosslinking. The dynamic covalent crosslinking network of the bioink allow an adaptable microenvironment contributing to the functional compartmentalization of endothelial cells and smooth muscle cells towards histological vasculature configurations. The engineered vasculature exhibited in vitro contraction in response to angiotensin II and significantly improved blood perfusion in mice hind limb ischemia model. In addition, the vascular network successfully prolonged the survival and function of surrounding human dermal fibroblasts (HDFs) postimplantation, which enhanced the healing of large full-thickness wounds. 

Proteomic analysis showed a significant enrichment of hypoxia-inducible factor-1 (HIF-1) signaling pathway and glycolysis/gluconeogenesis pathway in the engineered vasculature, implying that the three-dimensional interaction between HUVECs and VSMCs leads to enhanced glycolysis and cellular ATP content which play a role in the formation of vasculature-like structure via cytoskeleton remodeling and cell migration. Furthermore, GO enrichment analysis revealed upregulation of proteins associated with positive regulation of cell adhesion mediated by integrin, myosin II filament and actomyosin structure organization, suggesting that focal adhesion kinase (FAK) pathway participated in the morphogenesis process by coupling the microscopically adaptable environment to the vasculature organization via upregulation of integrin-mediated adhesion and glycolysis.

Altogether, this work presents a one-step bioprinting strategy of prevascularization in predesigned architecture for vascular tissue engineering.

This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, the Key Science and Technology Project of Guangzhou City, Guangdong Pearl River Talents Program and Funding by Science and Technology Projects in Guangzhou.

Contact：

WU Linping, Ph.D., Principal Investigator;

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China, 510530.

Email: wu_linping@gibh.ac.cn