Shear-Induced Patterning of Decellularized Skeletal Muscle Extracellular Matrix for Enhanced Myogenesis.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Severe skeletal muscle injuries lead to lasting functional impairments, creating a significant clinical need for effective regenerative strategies.
• Biomaterials that guide cellular behavior and provide environmental cues are crucial for enhancing muscle tissue repair.
• Current approaches often struggle to fully restore function due to limitations in mimicking the native muscle microenvironment.

Purpose of the Study:

• To engineer and pattern decellularized extracellular matrix (dECM) scaffolds with tunable biophysical properties for skeletal muscle regeneration.
• To investigate the impact of patterned dECM scaffolds on myogenic cell behavior and tissue remodeling.
• To evaluate the efficacy of these engineered scaffolds in a preclinical model of volumetric muscle loss.

Main Methods:

• Fabrication of dECM scaffolds using pH-driven fibrillogenesis and shear-based extrusion for controlled fibril assembly.
• Topographical patterning of scaffold nanoarchitecture to mimic native skeletal muscle ECM.
• In vitro assessment of cell alignment, phenotype, and scaffold remodeling.
• In vivo evaluation in a mouse model of volumetric muscle loss to assess muscle regeneration and functional integration.

Main Results:

• Demonstrated controlled fibril assembly and topographical patterning within skeletal muscle dECM scaffolds.
• Engineered scaffolds directed myogenic cell alignment, influenced cell phenotype, and facilitated scaffold remodeling.
• In a volumetric muscle loss model, dECM scaffolds promoted new myofiber formation and enhanced muscle regeneration.
• Scaffold and tissue remodeling facilitated better integration and functional recovery.

Conclusions:

• Patterned dECM scaffolds with tunable biophysical properties offer a promising strategy for skeletal muscle regeneration.
• These engineered materials effectively support myogenesis and tissue integration by mimicking native ECM and providing instructive cues.
• This fibrillar patterned dECM platform holds potential for advancing musculoskeletal regenerative therapies for traumatic injuries.