Aligned and Conductive 3D Collagen Scaffolds for Skeletal Muscle Tissue Engineering

Abstract

Skeletal muscle is characterized by its three-dimensional (3D) anisotropic architecture composed of highly aligned, organized, and electrically excitable muscle fibers that enable normal locomotion. Biomaterial-based tissue engineering approaches to repair skeletal muscle injuries are limited due to difficulties in combining 3D structural alignment (to guide cell/matrix organization) and electrical conductivity (to enable electrically excitable myotube assembly and maturation). In this work we successfully produced aligned and electrically conductive 3D collagen scaffolds using a freeze-drying approach. Conductive polypyrrole (PPy) microparticles were synthesized and directly mixed into a suspension of type I collagen and chondroitin sulfate followed by directional lyophilization. Scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and confocal microscopy analyses showed that directional solidification resulted in scaffolds with longitudinally aligned macropores (transverse plane: 155 ± 27 µm, longitudinal plane: 218 ± 49 µm) with homogeneously-distributed PPy content. Chronopotentiometry verified that PPy incorporation resulted in a five-fold increase in conductivity when compared to non-PPy containing collagen scaffolds without detrimentally affecting C2C12 mouse myoblast metabolic activity. Furthermore, the aligned scaffold microstructure provided contact guidance cues that directed myoblast growth and organization. Incorporation of PPy also promoted enhanced myotube formation and maturation as measured by myosin heavy chain (MHC) expression and number of nuclei per myotube. Together these data suggest that aligned and conductive 3D collagen scaffolds could be useful for skeletal muscle tissue engineering.

Recycled algae-based carbon materials as electroconductive 3D printed skeletal muscle tissue engineering scaffolds

“…Results represented the electrically conductive PCL/PANI scaffold with aligned structure enhances the myotube formation and maturation. Also, the electrically conductive and aligned collagen/polypyrrole (PPy) scaffold enhanced myoblast orientation and induced myotube formation [26]. The added effect of the combination of electrical stimulation together with an aligned structure on the myogenic differentiation and regenerative capacity was shown in other studies, as well [35,36].…”

“…These filaments are then stabilized for layer by layer fabrication of 3D scaffolds for various tissues including cartilage, bone, cornea and for neural and cardiac tissue engineering [16][17][18][19][20] as well as skeletal muscle [21][22][23][24]. The parallelaligned structure of the scaffold is an important parameter for structural biomimicry in the case of the latter [25,26].…”

A Review of Recent Advances in Natural Polymer-Based Scaffolds for Musculoskeletal Tissue Engineering

“…For instance, collagen mixed with conductive PPy nanoparticles promoted cell adhesion, growth, and proliferation [ 182 ]. Furthermore, enhanced myotube formation and maturation were found in another collagen/PPy implantation study [ 185 ].…”