Tunable viscoelastic hydrogels for vascularization: mechanism, design and applications

Abstract

Vascularization is crucial for fabricating large-scale functional artificial tissues and organs, and hydrogels are the most commonly used biomaterials for constructing microenvironments conducive to blood vessel formation. However, traditional static hydrogels lack the dynamic regulation of cell behavior similar to natural extracellular matrix (ECM) because they cannot replicate the viscoelasticity of ECM. Viscoelasticity is a key dynamic biomechanical signal for regulating the cell fate and is crucial for modulating vascular cell behavior. In recent years, tunable viscoelastic hydrogels (TVHs) based on reversible crosslinking have become highly promising biomaterials due to their capacity to mimic the viscoelasticity of ECM. Although some vascularization studies using TVHs have been conducted, and significant progress has been made, this emerging field lacks a systematic summary. Therefore, this review summarizes the recent advances of TVHs in vascularization, including the three major strategies for precisely controlling hydrogel viscoelasticity, the influence of hydrogel viscoelasticity on vascular cell fate, and the application of hydrogel viscoelasticity in regulating blood vessel formation. The prospects and challenges of TVHs are also discussed. This review aims to provide design principles for engineering TVHs capable of precisely controlling viscoelasticity and developing next-generation biomaterials for manufacturing vascularized artificial tissues and organs.