Biomimetic Electroconductive Nanofibrous Matrices for Skeletal Muscle Regenerative Engineering
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 stimulus-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, aligned conductive fibrous matrices were effective in promoting myoblast differentiation by upregulation of myogenic markers. The results demonstrated a promising potential of aligned conductive fibrous matrices for skeletal muscle regenerative engineering.
Around 40% of the human body mass consists of skeletal muscle. Musculoskeletal disorders such as muscle atrophy and fatty infiltration after rotator cuff injury lead to disability and pain and increase the rate of retear after rotator cuff surgery. The study showed the potential of novel engineered matrix to regenerate skeletal muscle by utilizing conductive material and nanofiber-based matrices. The incorporation of conductive material and aligned nanofibers as electrical and topographical cues significantly impacted cell viability and differentiation to support muscle regeneration.
The study demonstrated that electroconductive nanocomposite matrix can favorably modulate myoblast proliferation and differentiation. Future study will investigate the in vivo efficacy of the engineered matrix using a rat rotator cuff tear model to understand the ability of the engineered matrix in reducing the fatty infiltration.
KeywordsMuscle regeneration Nanofibrous matrices Conductive material Electrospinning
This work was funded by the NSF EFRI 1332329, NIH DP1AR068147, and NIH RO1 AR063698.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
- 1.Juhas M, Bursac N. Engineering skeletal muscle repair. Curr Opin Biotechnol. 2013;24(5):880–6.Google Scholar
- 2.Qazi TH, Mooney DJ, Pumberger M, Geissler S, Duda GN. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends. Biomaterials. 2015;53:502–21.Google Scholar
- 3.Yang HS, Ieronimakis N, Tsui JH, Kim HN, Suh KY, Reyes M, et al. Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy. Biomaterials. 2014;35(5):1478–86.Google Scholar
- 4.Jiang T, Carbone EJ, Lo KW-H, Laurencin CT. Electrospinning of polymer nanofibers for tissue regeneration. Prog Polym Sci. 2015;46:1–24.Google Scholar
- 5.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. Am J Sports Med. 2017;45(1):179–88.Google Scholar
- 6.Chen MC, Sun YC, Chen YH. Electrically conductive nanofibers with highly oriented structures and their potential application in skeletal muscle tissue engineering. Acta Biomater. 2013;9(3):5562–72.Google Scholar
- 7.Saveh-Shemshaki N, Nair LS, Laurencin CT. Nanofiber-based matrices for rotator cuff regenerative engineering. Acta Biomater. 2019;94:64–81.Google Scholar
- 8.Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK. Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res: Off J Soc Biomater, Jpn Soc Biomater Aust Soc Biomater Korean Soc Biomater. 2002;60(4):613–21.Google Scholar
- 9.Aviss K, Gough J, Downes S. Aligned electrospun polymer fibres for skeletal muscle regeneration. Eur Cell Mater. 2010;19(1):193–204.Google Scholar
- 10.Choi JS, Lee SJ, Christ GJ, Atala A, Yoo JJ. The influence of electrospun aligned poly (epsilon-caprolactone)/collagen nanofiber meshes on the formation of self-aligned skeletal muscle myotubes. Biomaterials. 2008;29(19):2899–906.Google Scholar
- 11.Balint R, Cassidy NJ, Cartmell SH. Conductive polymers: towards a smart biomaterial for tissue engineering. Acta Biomater. 2014;10(6):2341–53.Google Scholar
- 12.Lee JY, Bashur CA, Goldstein AS, Schmidt CE. Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. Biomaterials. 2009;30(26):4325–35.Google Scholar
- 13.Gilmore KJ, Kita M, Han Y, Gelmi A, Higgins MJ, Moulton SE, et al. Skeletal muscle cell proliferation and differentiation on polypyrrole substrates doped with extracellular matrix components. Biomaterials. 2009;30(29):5292–304.Google Scholar
- 14.Jun I, Jeong S, Shin H. The stimulation of myoblast differentiation by electrically conductive sub-micron fibers. Biomaterials. 2009;30(11):2038–47.Google Scholar
- 15.Tait JG, Worfolk BJ, Maloney SA, Hauger TC, Elias AL, Buriak JM, et al. Spray coated high-conductivity PEDOT:PSS transparent electrodes for stretchable and mechanically-robust organic solar cells. Sol Energy Mater Sol Cells. 2013;110:98–106.Google Scholar
- 16.Yang G, Kampstra KL, Abidian MR. High performance conducting polymer nanofiber biosensors for detection of biomolecules. Adv Mater. 2014;26(29):4954–60.Google Scholar
- 17.Abidian MR, Kim D-H, Martin DC. Conducting-polymer nanotubes for controlled drug release. Adv Mater. 2006;18(4):405–9.Google Scholar
- 18.Peramo A, Urbanchek MG, Spanninga SA, Povlich LK, Cederna P, Martin DC. In situ polymerization of a conductive polymer in acellular muscle tissue constructs. Tissue Eng Part A. 2008;14(3):423–32.Google Scholar
- 19.Lampin M, Warocquier-Clérout R, Legris C, Degrange M, Sigot-Luizard MF. Correlation between substratum roughness and wettability, cell adhesion, and cell migration. J Biomed Mater Res. 1997;36(1):99–108.Google Scholar
- 20.Köunönen M, Hormia M, Kivilahti J, Hautaniemi J, Thesleff I. Effect of surface processing on the attachment, orientation, and proliferation of human gingival fibroblasts on titanium. J Biomed Mater Res. 1992;26(10):1325–41.Google Scholar
- 21.Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-inspired surface chemistry for multifunctional coatings. Science. 2007;318(5849):426–30.Google Scholar
- 22.Tsai WB, Chen WT, Chien HW, Kuo WH, Wang MJ. Poly(dopamine) coating to biodegradable polymers for bone tissue engineering. J Biomater Appl. 2014;28(6):837–48.Google Scholar
- 23.Tang X, Khan Y, Laurencin C. Electroconductive nanofiber scaffolds for muscle regenerative engineering. Front Bioeng Biotechnol. 2016.Google Scholar
- 24.Ding Y, Invernale MA, Sotzing GA. Conductivity trends of PEDOT-PSS impregnated fabric and the effect of conductivity on electrochromic textile. ACS Appl Mater Interfaces. 2010;2(6):1588–93.Google Scholar
- 25.Jo S, Kang SM, Park SA, Kim WD, Kwak J, Lee H. Enhanced adhesion of preosteoblasts inside 3D PCL scaffolds by polydopamine coating and mineralization. Macromol Biosci. 2013;13(10):1389–95.Google Scholar
- 26.Hong KH, Oh KW, Kang TJ. Preparation of conducting nylon-6 electrospun fiber webs by the in situ polymerization of polyaniline. J Appl Polym Sci. 2005;96(4):983–91.Google Scholar
- 27.Kim MS, Jun I, Shin YM, Jang W, Kim SI, Shin H. The development of genipin-crosslinked poly(caprolactone) (PCL)/gelatin nanofibers for tissue engineering applications. 2010;10(1):91–100.Google Scholar
- 28.Wakelam MJ. The fusion of myoblasts. The Biochemical Journal. 1985;228(1):1–12.Google Scholar