Enhanced piezoelectric collagen with aligned microstructure for synergistic electro-topological skeletal muscle regeneration.

Abstract

Volumetric muscle loss (VML) often leads to irreversible functional impairment due to limited endogenous regeneration and poor outcomes of current therapies. Collagen fibers are piezoelectric biomaterials and key components of the skeletal muscle extracellular matrix. With excellent biocompatibility, deformability, and capacity to promote myocyte proliferation and differentiation, collagen holds great promise for muscle repair and regeneration. However, the inherently weak piezoelectricity, structural disorder, and insufficient mechanical properties limit the practical application. This study introduces a co-assembly strategy using gallic acid (GA) to enhance the piezoelectric performance of collagen through interactions between the phenolic hydroxyl groups of GA and collagen, which may contribute to a more ordered hydrogen-bonding network and promote the oriented arrangement of phenolic hydroxyl groups. On this basis, a collagen fiber-based piezoelectric material (CFPM) was fabricated by combining salting-out and pre-stretching, exhibiting stable piezoelectric output, skeletal muscle-matched mechanical properties, and an anisotropic structure. Under ultrasound activation, CFPM generates electrical signals that synergize with topological cues to promote myoblast differentiation and the formation of aligned myotubes. In a rat VML model, CFPM implantation with ultrasound significantly enhances muscle regeneration, reduces fibrosis, and improves functional recovery. Collectively, the enhanced piezoelectric collagen with aligned microstructure developed in this study represents a promising biomaterial strategy for VML repair.