Wet-Spun Trojan Horse Cell Constructs for Engineering Muscle

Area of Science:

• Biomaterials Engineering
• Regenerative Medicine
• Tissue Engineering

Background:

• Volumetric Muscle Loss (VML) and muscle diseases like Muscular Dystrophy require effective muscle regeneration strategies.
• Additive Biofabrication (AdBiofab) offers potential for creating 3D regenerative skeletal muscle tissue constructs (skMTCs).
• Traditional 3D printing may face limitations in balancing cell type, construct size, and material cyto-compatibility compared to methods like wet-spinning.

Purpose of the Study:

• To fabricate and evaluate biosynthetic alginate fibers containing muscle precursor cells (MPCs) for dystrophin-expressing cell delivery in the mdx mouse model of Duchenne Muscular Dystrophy (DMD).
• To introduce a novel method for creating 3D layered wet-spun alginate skMTCs for bulk MPC delivery to VML lesions.
• To conceptualize "Trojan Horse" Fiber MTCs (TH-fMTCs) and 3d Mesh-MTCs (TH-mMTCs) for regenerative MPC delivery.

Main Methods:

• Fabrication of alginate fibers and 3D layered constructs using wet-spinning technology.
• Incorporation of muscle precursor cells (MPCs) within the alginate biomaterial.
• In vivo testing in the mdx mouse model for DMD and evaluation for VML repair applications.

Main Results:

• Demonstrated successful fabrication of alginate fibers and 3D mesh constructs containing MPCs.
• Showcased the potential of these constructs for delivering dystrophin-expressing cells in a DMD mouse model.
• Introduced novel TH-fMTCs and TH-mMTCs as promising delivery vehicles for regenerative MPCs.

Conclusions:

• Wet-spinning offers an alternative biofabrication method for creating regenerative skeletal muscle tissue constructs.
• Alginate-based TH-fMTCs and TH-mMTCs show potential for treating muscular dystrophy and repairing VML injuries.
• This work advances the development of cell-laden biomaterials for skeletal muscle regeneration.