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bioRxiv · 10.1101/2025.08.20.671328

Melt Electrowritten Microfiber-Hydrogel Composite Scaffolds for Aligned Muscle Tissue Engineering

Rauff, A.·Liashenko, I.·Lippa, C.·Nightheart, S. R.·Jones, K. A.·Dalton, P. D.·Guldberg, R. E.·Willett, N.
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Abstract

Effective regeneration of skeletal muscle with highly aligned fiber architecture remains a significant challenge in tissue engineering. Structural alignment of muscle constructs along with mechanical integrity are crucial for effective engineering of grafts and microphysiological systems. This study engineered a novel composite microfiber-hydrogel platform using melt-electrowriting (MEW) to fabricate high precision microfiber scaffolds from poly({varepsilon}-caprolactone). Three MEW scaffold designs (Isotropic, Aligned T with perpendicular reinforcements, and Aligned X with angled fiber bridges) were developed and fabricated into composite scaffolds with collagen hydrogels and seeded with myoblasts. Aligned X scaffolds with cross-bridge reinforcements exhibited enhanced mechanical strength and continuous alignment without structural interruption that led to highly aligned and multinucleated cellular organization. The incorporation of collagen hydrogel in composite constructs improved cell seeding efficiency, viability, and metabolic activity compared to scaffolds alone. All scaffold designs provided fiber reinforcement that prevented hydrogel contraction over extended culture periods. Critically, the Aligned X composite constructs significantly increased myoblast differentiation and myotube maturation, evidenced by increased myosin heavy chain expression and myotube diameter. Overall, this composite microfiber-hydrogel approach provides a scalable, structurally stable, and highly aligned platform tailored for enhanced muscle tissue engineering applications, representing an advancement towards addressing clinical challenges associated with muscle injuries.

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Rauff, A., Liashenko, I., Lippa, C., Nightheart, S. R., Jones, K. A., Dalton, P. D., Guldberg, R. E., Willett, N.. 2025-08-24. Melt Electrowritten Microfiber-Hydrogel Composite Scaffolds for Aligned Muscle Tissue Engineering. https://doi.org/10.1101/2025.08.20.671328

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