Biomimetic electroconductive nanofibrous matrices for skeletal muscle regenerative engineering

Xiaoyan Tang^{1

2

3

4}, Nikoo Saveh-Shemshaki^{1

2

4

5}, Ho-Man Kan^{1

2

4}, Yusuf Khan^{1

2

3

4

5}, Cato T Laurencin^{1

2

3

4

5

6

7}

Affiliations

¹ Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Farmington, CT 06030, USA.
² Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
³ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁴ Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
⁵ Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁶ Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁷ Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030, USA.

PMID: 33426269
PMCID: PMC7793553
DOI: 10.1007/s40883-019-00136-z

Biomimetic electroconductive nanofibrous matrices for skeletal muscle regenerative engineering

Xiaoyan Tang et al. Regen Eng Transl Med. 2020 Jun.

. 2020 Jun;6(2):228-237.

doi: 10.1007/s40883-019-00136-z. Epub 2019 Dec 3.

Authors

Xiaoyan Tang^{1

2

3

4}, Nikoo Saveh-Shemshaki^{1

2

4

5}, Ho-Man Kan^{1

2

4}, Yusuf Khan^{1

2

3

4

5}, Cato T Laurencin^{1

2

3

4

5

6

7}

Affiliations

¹ Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Farmington, CT 06030, USA.
² Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
³ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁴ Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
⁵ Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁶ Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁷ Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030, USA.

PMID: 33426269
PMCID: PMC7793553
DOI: 10.1007/s40883-019-00136-z

Abstract

The regeneration of the muscles of the rotator cuff represents a grand challenge in musculoskeletal regenerative engineering. Several types of matrices have been proposed for skeletal muscle regeneration. However, biomimetic matrices to promote muscle regeneration and mimic native muscle tissue have not been successfully engineered. Besides topographical cues, an electrical stimulus may serve as a critical cue to improve interactions between materials and cells in scenarios fostering muscle regeneration. In this in vitro study, we engineered a novel stimuli-responsive conductive nanocomposite matrix, and studied its ability to regulate muscle cell adhesion, proliferation, and differentiation. Electroconductive nanocomposite matrices demonstrated tunable conductivity and biocompatibility. Under the optimum concentration of conductive material, the matrices facilitated muscle cell adhesion, proliferation, and differentiation. Importantly, conductive aligned fibrous matrices were effective in promoting myoblast differentiation by upregulation of myogenic markers. The results demonstrated promising potential of aligned conductive fibrous matrices for skeletal muscle regenerative engineering.

Keywords: Conductive material; Electrospinning; Muscle regeneration; Nanofibrous matrices.

PubMed Disclaimer

Conflict of interest statement

Competing interests: No competing interests.

Figures

**Fig. 1.. Preparation of conductive nanocomposite matrices.**
Schematic illustration of the preparation of conductive nanocomposite matrices for muscle regeneration.

**Fig. 2.. Characterization of nanocomposite matrices.**
A) SEM images showing nanotopography preservation and PEDOT:PSS distribution (8000x) **(i)** Pure PCL matrices **(ii)** Dopamine polymerized PCL matrices (DOPA/PCL) **(iii)** 1% PEDOT: PSS coated on dopamine polymerized PCL (1% PEDOT:PSS/DOPA/PCL) **(iv)**10% PEDOT: PSS coated on dopamine polymerized PCL (10% PEDOT:PSS/DOPA/PCL) **(v)** 33% PEDOT:PSS coated on dopamine polymerized PCL (33% PEDOT:PSS/DOPA/PCL) **(vi)** 100% PEDOT:PSS coated on dopamine polymerized PCL (100% PEDOT:PSS/DOPA/PCL). B) Contact angle analysis for **(i)** Pure PCL **(ii)** Dopamine polymerized PCL. C) Sheet Resistance of different concentration of PEDOT:PSS coating.

**Fig.3.. Biocompatibility characterization of conductive matrices**
A) Representative fluorescent images of C2C12 myoblasts cultured on different groups on day 3 and stained using a Live/ Dead Cell Viability kit (green, viable cells; red, dead cells), **(i)** Pure PCL matrices **(ii)** Dopamine polymerized PCL matrices (DOPA/PCL) **(iii)** 1% PEDOT: PSS coated on dopamine polymerized PCL (1% PEDOT:PSS/DOPA/PCL) **(iv)**10% PEDOT: PSS coated on dopamine polymerized PCL (10% PEDOT:PSS/DOPA/PCL) **(v)** 33% PEDOT:PSS coated on dopamine polymerized PCL (33% PEDOT:PSS/DOPA/PCL) **(vi)** 100% PEDOT:PSS coated on dopamine polymerized PCL (100% PEDOT:PSS/DOPA/PCL)**. B)** proliferation study on day 3, day 7 and day 14, Mean ± SD; n = 3–5 samples per group, *P < 0.05 between different matrix groups C) SEM images of cell-seeded matrices on day 3, **(i)** Pure PCL matrices **(ii)** Dopamine polymerized PCL matrices (DOPA/PCL) **(iii)** 1% PEDOT: PSS coated on dopamine polymerized PCL (1% PEDOT:PSS/DOPA/PCL) **(iv)**10% PEDOT: PSS coated on dopamine polymerized PCL (10% PEDOT:PSS/DOPA/PCL) **(v)** 33% PEDOT:PSS coated on dopamine polymerized PCL (33% PEDOT:PSS/DOPA/PCL) **(vi)** 100% PEDOT:PSS coated on dopamine polymerized PCL (100% PEDOT:PSS/DOPA/PCL).

**Fig.4.. Myogenic differentiation**
A) Representative fluorescent images of C2C12 cells cultured on day 14, **(i)**100% PEDOT: PSS/DOPA/PCL, **(ii)** 33% PEDOT: PSS/DOPA/PCL, **(iii)** 10% PEDOT: PSS/DOPA/PCL, **(iv)**1% PEDOT: PSS/DOPA/PCL, **(v)** DOPA/PCL, and **(vi)** PCL, sarcomeric-myosin heavy chain (green), nuclei (blue), scale bars indicate 100 μm. B) Representative images of C2C12 myotube formation on **(i)** 1% PEDOT: PSS/DOPA/PCL, **(ii)** 10% PEDOT: PSS/DOPA/PCL, scale bars indicate 50 μm. C) Impact of PEDOT: PSS on myogenic differentiation (gene expression) on day 8.

**Fig.5.. Effect of topographical on myoblast differentiation.**
A) Representative images day 8 factin/dapi staining ofmyoblast cells (i) A/10% PEDOT: PSS/DOPA/PCL electrospun nanofibers (ii) R/10% PEDOT:PSS/DOPA/PCL electrospun nanofibers (iii) Pure A/PCL electrospun nanofibers (iv) Pure R/PCL electrospun nanofibers. B) Protein expression Tnnt1 D14 (random and alignment). C) Normalized protein expression Tnnt1 D14 (random and alignment).

**Fig.6.. Effect of topographical on myotube formation.**
A) Representative images of MHC/PI staining of C2C12 cells on (i) A/10% PEDOT:PSS/DOPA/PCL (ii) R/10% PEDOT:PSS/DOPA/PCL (iii) A/PCL (iv) R/PCL. B) (i) Quantification of the myotube number and (ii) myotube length formed in (A) * p<0.05 significantly different.

See this image and copyright information in PMC

References

1. Juhas M, Bursac NJCoib. Engineering skeletal muscle repair. 2013;24(5):880–6. - PMC - PubMed
1. Qazi TH, Mooney DJ, Pumberger M, Geissler S, Duda GNJB. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends. 2015;53:502–21. - PubMed
1. Yang HS, Ieronimakis N, Tsui JH, Kim HN, Suh K-Y, Reyes M, et al. Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy. 2014;35(5):1478–86. - PubMed
1. Jiang T, Carbone EJ, Lo KW-H, Laurencin CTJPipS. Electrospinning of polymer nanofibers for tissue regeneration. 2015;46:1–24.
1. Sevivas N, Teixeira FG, Portugal R, Araújo L, Carriço LF, Ferreira N, et al. Mesenchymal stem cell secretome: a potential tool for the prevention of muscle degenerative changes associated with chronic rotator cuff tears. The American journal of sports medicine. 2017;45(1):179–88. - PubMed

Grants and funding

LinkOut - more resources

Full Text Sources
- Europe PubMed Central
- PubMed Central
Other Literature Sources
- The Lens - Patent Citations Database

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Biomimetic electroconductive nanofibrous matrices for skeletal muscle regenerative engineering

Affiliations

Biomimetic electroconductive nanofibrous matrices for skeletal muscle regenerative engineering

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources