Pigmented Silk Nanofibrous Composite for Skeletal Muscle Tissue Engineering

Abstract

Skeletal muscle tissue engineering (SMTE) employs designed biomaterial scaffolds for promoting myogenic differentiation of myoblasts to functional myotubes. Oxidative stress plays a significant role in the biocompatibility of biomaterials as well as in the fate of myoblasts during myogenesis and is also associated with pathological conditions such as myotonic dystrophy. The inherent electrical excitability of muscle cells inspired the use of electroactive scaffolds for SMTE. Conducting polymers attracted the attention of researchers for their use in muscle tissue engineering. However, poor biocompatibility, biodegradability and development of oxidative stress associated immunogenic response limits the extensive use of synthetic conducting polymers for SMTE. In order to address the limitations of synthetic polymers, intrinsically electroactive and antioxidant silk fibroin/melanin composite films and electrospun fiber mats were fabricated and evaluated as scaffolds for promoting myogenesis in vitro. Melanin incorporation modulated the thermal stability, electrical conductivity of scaffolds, fiber alignment in electrospun mats and imparted good antioxidant properties to the scaffolds. The composite electrospun scaffolds promoted myoblast assembly and differentiation into uniformly aligned high aspect ratio myotubes. The results highlight the significance of scaffold topography along with conductivity in promoting myogenesis and the potential application of silk nanofibrous composite as electoractive platform for SMTE.

Anisotropic Materials for Skeletal‐Muscle‐Tissue Engineering

“…Recently, Manchineela and colleagues reported the addition of melanin, a naturally occurring polymer pigment with conductive properties, to silk fibroin, which produced nanofibers with better fiber alignment than fibers produced with silk fibroin alone. [96] While these silk-melanin nanofibers do not achieve the degree of alignment seen in other systems discussed here, there is a dramatic difference in alignment between the two conditions, and a significant advantage of this system is the utilization of naturally-derived materials. Aligned silk fibroin-melanin (SM) nanofibers were conductive and induced enhanced myogenic differentiation of C2C12s as compared to silk fibroin (SF) nanofibers, SF films and SM films, indicative of the importance of both topographic and conductivity cues.…”

Mammalian Skeletal Muscle Fibres Promote Non-Muscle Stem Cells and Non-Stem Cells to Adopt Myogenic Characteristics

“…To that end, we envisage using de-cellularised muscle from bigger (commercial) species (bovine), which can be generated in large quantities [35]. A number of advances have recently been made in creating materials often involving electrospinning, that direct either a partial or complete move away from man/animal tissues for use in muscle-based pathologies [36]. Many of the artificial materials support the differentiation and fusion of muscle stem cells, into ordered myotubes [37].…”

From Dermal Patch to Implants—Applications of Biocomposites in Living Tissues

“…However, these polymers have shown to present not just toxicity but also reduced biodegradability. To overcome some of these challenges, Manchineella et al [78] explored the use of silk fibroin combined with melanin in the development of an electroactive biocomposite scaffold. While silk fibroin (extracted from silkworm cocoons) has good biodegradability and biocompatibility, the conduction property of the biocomposite originated from the addition of melanin.…”