Melt Electrowritten Microfiber-Hydrogel Composite Scaffolds with Local Cross-bridging Reinforcements for Aligned...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Effective skeletal muscle regeneration requires aligned fiber architecture and mechanical integrity, posing challenges in tissue engineering.
• Existing methods struggle to maintain structural alignment and mechanical cohesion in engineered muscle constructs.
• Microphysiological systems and grafts demand scaffolds that mimic native muscle tissue's structural properties.

Purpose of the Study:

• To introduce a composite microfiber-hydrogel platform using melt electrowriting (MEW) for creating reinforced, aligned muscle tissue scaffolds.
• To evaluate the impact of different MEW scaffold designs (Isotropic, Aligned T, Aligned X) on mechanical properties, cellular organization, and myogenic differentiation.
• To assess the role of collagen hydrogel incorporation in enhancing cell viability and preventing scaffold contraction.

Main Methods:

• Fabrication of three MEW scaffold designs (Isotropic, Aligned T, Aligned X) with varying fiber reinforcement architectures.
• Development of composite scaffolds by integrating collagen hydrogels with MEW microfiber structures.
• Seeding scaffolds with myoblasts and evaluating cell behavior, myogenic differentiation, and mechanotransduction signaling (YAP localization).

Main Results:

• Aligned X scaffolds demonstrated superior mechanical strength and continuous fiber alignment, leading to highly organized, multinucleated cellular structures.
• Collagen hydrogel incorporation improved cell seeding efficiency, viability, and metabolic activity, while preventing hydrogel contraction.
• The Aligned X architecture significantly enhanced myogenic differentiation, evidenced by increased myosin heavy chain expression and myotube diameter, linked to topographical cues and mechanotransduction.

Conclusions:

• The composite microfiber-hydrogel platform, particularly the Aligned X architecture, provides a structurally stable and highly aligned scaffold for advanced muscle tissue engineering.
• This approach overcomes challenges in soft tissue contraction and enables scalable, mechanically robust engineered muscle constructs.
• The findings represent a significant advancement towards addressing clinical needs in skeletal muscle injury repair and regeneration.