Annals of Biomedical Engineering

, Volume 44, Issue 6, pp 2036–2048 | Cite as

Cell-Instructive Graphene-Containing Nanocomposites Induce Multinucleated Myotube Formation

  • Akhil Patel
  • Yingfei Xue
  • Shilpaa Mukundan
  • Lisa C. Rohan
  • Vinayak Sant
  • Donna B. Stolz
  • Shilpa SantEmail author
Emerging Trends in Biomaterials Research


Myoblast differentiation is a key step in myogenesis and has long been considered to be controlled mainly by biochemical cues such as growth factors. However, the tissue engineering approaches based on biochemical cues demonstrate low reproducibility as a precise spatial control over their bioactivity is challenging. Recently, substrate micro/nano-structure and electro-responsive properties are recognized for their important roles in myoblast differentiation. In this study, we hypothesized that engineering biophysical features such as nano/micro-fibrous structure and conductive properties into a single biomaterial scaffold will instruct the myoblasts to differentiate into multinucleated myotubes even in the absence of differentiation media. We fabricated nanocomposite scaffolds composed of conductive graphene nanosheets and polycaprolactone (PCL), a widely used biocompatible material. The resulting graphene-PCL scaffolds possess excellent conductivity due to graphene nanosheets and great processability, biodegradability and elastic mechanical properties conferred by PCL. Additionally, physicochemical and mechanical properties of nanocomposite scaffolds can be tuned by varying graphene concentration. Further, graphene-PCL nanocomposites and their 8-week degradation products exhibited remarkable cytocompatibility and promoted adhesion and proliferation of C2C12 mouse myoblast cells. Importantly, these nanocomposite scaffolds induced graphene concentration-dependent differentiation of C2C12 cells into multinucleated myotubes even in normal growth media suggesting their cell-instructive potential. Thus, graphene-PCL nanocomposite scaffolds can serve as a strategy to promote skeletal muscle regeneration without biochemical cues.


Graphene nanosheet Myoblast differentiation Electrospinning Polycaprolactone Cell-instructive scaffolds Biologic-free 



The authors acknowledge Material Characterization Lab, University of Pittsburgh for access to contact angle goniometer and Dr. Tracy Cui lab for access to conductivity measurement. SS acknowledges financial support (start-up funds) from the Department of Pharmaceutical Sciences at University of Pittsburgh.


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Copyright information

© Biomedical Engineering Society 2016

Authors and Affiliations

  • Akhil Patel
    • 1
  • Yingfei Xue
    • 1
  • Shilpaa Mukundan
    • 1
  • Lisa C. Rohan
    • 1
  • Vinayak Sant
    • 1
  • Donna B. Stolz
    • 2
    • 3
  • Shilpa Sant
    • 1
    • 4
    • 5
    Email author
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of PittsburghPittsburghUSA
  2. 2.Center for Biologic ImagingUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Departments of Cell Biology and PathologyUniversity of PittsburghPittsburghUSA
  4. 4.Department of BioengineeringUniversity of PittsburghPittsburghUSA
  5. 5.McGowan Institute for Regenerative MedicinePittsburghUSA

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