Stretchable Alginate/GelMA Interpenetrating Network (IPN) hydrogel microsprings based on coaxial microfluidic technique for skeletal muscle tissue engineering

The emulation of the natural organization and contractile properties of native stretchable tissues have crucial implications for skeletal muscle tissue engineering (SMTE). Helical structures, ubiquitous in nature and endowed with unique mechanical characteristics, have recently gained significant traction in SMTE applications. However, developing hierarchical hydrogel-based scaffolds that both replicate exceptional mechanical properties and control cellular organization remains challenging. Herein, we present an interpenetrating network (IPN) hydrogel synthesized from alginate and GelMA materials, to fabricate stretchable helical hydrogel microsprings via a coaxial microfluidic chip, showcasing superior elasticity attributed to helical structures. These hydrogel microsprings showed the micro- and nanoscale patterned groove/ridge helical structures, which microsprings demonstrated the ability to guide myoblast alignment and elongation along the longitudinal axis of the helical structures in vitro. Moreover, when the hydrogel microsprings were tailored into suitable sizes and utilized as injectable micro-scaffolds, they provided a conducive mechanical microenvironment for enhancing cell infiltration and facilitating muscle tissue regeneration in situ in rat models. This study offers a promising strategy for creating stretchable helical hydrogel microsprings that integrate distinctive microand nanoscale features, which not only showed the potential as biomimetic elastic scaffolds for guiding 3D cellular orientation in vitro but also as injectable carriers for enhancing skeletal muscle tissue regeneration in vivo.