Accelerating neovascularization and kidney tissue formation with a 3D vascular scaffold capturing native vascular structure

Abstract

Establishing an adequate vascularization of three-dimensional (3D) bioengineered tissues remains a critical challenge. We previously fabricated a vascular scaffold using the vascular corrosion casting technique, which provides a similar 3D geometry of native kidney vasculature. In this study, we functionalized the collagen vascular scaffold with a controlled release of vascular endothelial growth factor (VEGF vascular scaffold) to further promote vascularization. The VEGF vascular scaffold showed improved angiogenic capability in 2-dimensional (2D) and 3D in vitro settings. Implantation of the VEGF vascular scaffold seeded with human renal cells into a rat kidney demonstrated enhanced implant vascularization and reduced apoptosis of implanted human renal cells. Hybrid renal tubule-like structures composed of implanted human and migrated host renal cells were formed. This work highlights the critical role of early vascularization of the geometrically mimetic vascular scaffold using the VEGF incorporated vascular scaffold in reducing apoptosis of implanted cells as well as the formation of renal tissue structures. Statement of significance One major challenge in the clinical translation of three-dimensional tissue-engineered constructs is establishing adequate vascularization. A newly developed collagen-based vascular scaffold using the corrosion casting technique provides a similar geometry of native renal vasculature. Incorporation of a potent angiogenic growth factor into this vascular scaffold results in controlled release and facilitates endothelialization of the scaffold. Rapid vascularization prevents apoptosis of the seeded cells and enhances the reorganization of cells into renal tubule like structures. This unique functional vascular scaffold with controlled release of angiogenic growth factor may provide a solution for accelerated clinical translation of tissue-engineered three-dimensional constructs. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Statement of significance One major challenge in the clinical translation of three-dimensional tissue-engineered constructs is establishing adequate vascularization. A newly developed collagen-based vascular scaffold using the corrosion casting technique provides a similar geometry of native renal vasculature. Incorporation of a potent angiogenic growth factor into this vascular scaffold results in controlled release and facilitates endothelialization of the scaffold. Rapid vascularization prevents apoptosis of the seeded cells and enhances the reorganization of cells into renal tubulelike structures. This unique functional vascular scaffold with controlled release of angiogenic growth factor may provide a solution for accelerated clinical translation of tissue-engineered three-dimensional constructs.