Temporal Tissue Remodeling in Volumetric Muscle Injury with Endothelial Cell-Laden Patterned Nanofibrillar...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Severe musculoskeletal trauma often results in incomplete muscle regeneration.
• Current therapies struggle with muscle healing due to impaired repair programs and poor early revascularization.
• Understanding early muscle remodeling in response to engineered therapies is crucial.

Purpose of the Study:

• To investigate how endothelial cell (EC) patterning within engineered constructs influences temporal and histomorphological muscle remodeling post-injury.
• To evaluate the impact of nanotopographically patterned scaffolds on muscle repair and regeneration.

Main Methods:

• Mice with volumetric muscle loss (VML) injury received engineered constructs with aligned or random EC-patterned collagen nanofibrils.
• Remodeling was assessed at 2, 7, and 21 days post-injury.
• Histomorphological analysis included vascular density, myogenesis, muscle cross-sectional area, and collagen deposition.

Main Results:

• All groups showed increased vascular density and myogenesis over 21 days.
• Patterned EC constructs preserved muscle mass, unlike acellular controls which showed significant atrophy.
• EC constructs increased fibrous remodeling and collagen deposition compared to acellular controls.

Conclusions:

• Nanotopographically patterned EC-laden constructs guide early muscle remodeling.
• These constructs promote muscle mass retention through myo-vascular independent pathways.
• This approach offers a potential strategy for improving outcomes after severe musculoskeletal trauma.