Engineering of the microenvironment to accelerate vascular regeneration

Abstract

Blood vessels are crucial for tissue development, functionality, and homeostasis and are typically a determinant in the progression of healing and regeneration. The tissue microenvironment provides physicochemical cues that affect cellular function, and the study of the microenvironment can be accelerated by the engineering of approaches capable of mimicking various aspects of the microenvironment. In this review, we introduce the major components of the vascular niche and focus on the roles of oxygen and the extracellular matrix (ECM). We demonstrate how vascular engineering approaches enhance our understanding of the microenvironment's impact on the vasculature towards vascular regeneration and describe the current limitations and future directions towards clinical utilization.

Keywords: extracellular matrix; hypoxia; regeneration; vascular engineering.

Figure 1.. Engineering Hydrogels to Model ECM for Vascular Regeneration.

Schematic illustration of the various engineering approaches utilized to create ECM-mimicking hydrogels for modeling and facilitating vascular regeneration. While a given technique is depicted as influencing one aspect of ECM modeling, such as structure, mechanics, or composition, a given approach often influences more than one aspect of ECM modeling. Created using Biorender.com.

Figure 2.. Engineering Approaches to Recapitulate Hypoxia.

(left) Microfluidic devices have been utilized to incorporate hypoxic conditions in studying vascular regeneration. (right) Hydrogels with oxygen gradients and constant hypoxia have also been employed for studying the effects of varying oxygen levels during vascularization. Created using Biorender.com.

Figure 3.. Examples of ECM and Oxygen Level Modeling.

Schematic and data from A. Schnellmann et al. modeling ECM stiffening that lead to compromised microvascular phenotype. B. Sayer et al. modeling ECM patterning with high-resolution photographing, modulating endothelial sprout migration, C. Shih et al. demonstrating endothelial cell migration and proliferation under an oxygen gradient using microfluidics, and D. Blatchley et al. illustrating how low oxygen environments mediate endothelial cell cluster formation. Schematics and results were slightly modified for formatting and clarity. Schematics Created using Biorender.com.