Data availability
All data supporting the findings of this study are included within the article and its Supplementary Information files. Additional datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.
References
-
Zhou, J. & Shi, Y. Mesenchymal stem/stromal cells (MSCs): origin, immune regulation, and clinical applications. Cell Mol. Immunol. 20, 555–557. https://doi.org/10.1038/s41423-023-01034-9 (2023).
-
Song, N., Scholtemeijer, M. & Shah, K. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol. Sci. 41, 653–664. https://doi.org/10.1016/j.tips.2020.06.009 (2020).
-
Hofer, H. R. & Tuan, R. S. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell. Res. Ther. 7, 131. https://doi.org/10.1186/s13287-016-0394-0 (2016).
-
Müller, L. et al. Immunomodulatory properties of mesenchymal stromal cells: an update. Front. Cell. Dev. Biol. 9, 637725. https://doi.org/10.3389/fcell.2021.637725 (2021).
-
Vater, C., Kasten, P. & Stiehler, M. Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater. 7, 463–477. https://doi.org/10.1016/j.actbio.2010.07.037 (2011).
-
Ferreira, J. R. et al. Mesenchymal stromal cell secretome: influencing therapeutic potential by cellular pre-conditioning. Front. Immunol. 9–2018. https://doi.org/10.3389/fimmu.2018.02837 (2018).
-
Almalki, S. G. & Agrawal, D. K. Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation 92, 41–51. https://doi.org/10.1016/j.diff.2016.02.005 (2016).
-
Ghasemi-Mobarakeh, L. et al. Structural properties of scaffolds: crucial parameters towards stem cells differentiation. World J. Stem Cells. 7, 728–744. https://doi.org/10.4252/wjsc.v7.i4.728 (2015).
-
Wu, D. et al. Bioinstructive scaffolds enhance stem cell engraftment for functional tissue regeneration. Nat. Mater. 24, 1364–1374. https://doi.org/10.1038/s41563-025-02212-y (2025).
-
Su, N. et al. Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: A new dimension in cell-material interaction. Biomaterials 141, 74–85. https://doi.org/10.1016/j.biomaterials.2017.06.028 (2017).
-
Zulkifli, M. Z. A., Nordin, D., Shaari, N. & Kamarudin, S. K. Overview of electrospinning for tissue engineering applications. Polym. (Basel). 15 https://doi.org/10.3390/polym15112418 (2023).
-
Pisani, S. et al. Assessment of different manufacturing techniques for the production of bioartificial scaffolds as soft organ transplant substitutes. Front. Bioeng. Biotechnol. 11 https://doi.org/10.3389/fbioe.2023.1186351 (2023).
-
Ejiohuo, O. A perspective on the synergistic use of 3D printing and electrospinning to improve nanomaterials for biomedical applications. Nano Trends. 4, 100025. https://doi.org/10.1016/j.nwnano.2023.100025 (2023).
-
Abdullah, K. K. & Molnár, K. Current trends and future prospects of integrating electrospinning with 3d printing techniques for mimicking bone extracellular matrix scaffolds. J. Polym. Sci. 63, 1481–1504. https://doi.org/10.1002/pol.20241010 (2025).
-
Pisani, S. et al. Nanofibrous scaffolds’ ability to induce mesenchymal stem cell differentiation for soft tissue regenerative applications. Pharmaceuticals 18, 239 (2025).
-
Mishra, A., Modi, U., Sharma, R., Bhatia, D. & Solanki, R. Biochemical and biophysical cues of the extracellular matrix modulates stem cell fate: progress and prospect in extracellular matrix mimicking biomaterials. Biomedical Eng. Adv. 9, 100143. https://doi.org/10.1016/j.bea.2024.100143 (2025).
-
Khan, A. R. et al. Advances in smart hybrid scaffolds: A strategic approach for regenerative clinical applications. Eng. Regeneration. 6, 85–110. https://doi.org/10.1016/j.engreg.2025.02.002 (2025).
-
Mauro, A. Satellite cell of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 9, 493–495. https://doi.org/10.1083/jcb.9.2.493 (1961).
-
Ganassi, M., Badodi, S., Wanders, K., Zammit, P. S. & Hughes, S. M. Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis. Elife 9 https://doi.org/10.7554/eLife.60445 (2020).
-
Yang, W. & Hu, P. Skeletal muscle regeneration is modulated by inflammation. J. Orthop. Translat. 13, 25–32. https://doi.org/10.1016/j.jot.2018.01.002 (2018).
-
Alarcin, E. et al. Current strategies for the regeneration of skeletal muscle tissue. Int. J. Mol. Sci. 22 https://doi.org/10.3390/ijms22115929 (2021).
-
Helal, M. A. M., Shaheen, N. E. M. & Abu Zahra, F. A. Immunomodulatory capacity of the local mesenchymal stem cells transplantation after severe skeletal muscle injury in female rats. Immunopharmacol. Immunotoxicol. 38, 414–422. https://doi.org/10.1080/08923973.2016.1222617 (2016).
-
Yu, D. et al. Myogenic differentiation of stem cells for skeletal muscle regeneration. Stem Cells Int. 2021 (8884283). https://doi.org/10.1155/2021/8884283 (2021).
-
Stern-Straeter, J. et al. Evaluation of the effects of different culture media on the myogenic differentiation potential of adipose tissue- or bone marrow-derived human mesenchymal stem cells. Int. J. Mol. Med. 33, 160–170. https://doi.org/10.3892/ijmm.2013.1555 (2014).
-
Goldshmid, R. et al. Modulus-dependent effects on neurogenic, myogenic, and chondrogenic differentiation of human mesenchymal stem cells in three-dimensional hydrogel cultures. J. Biomed. Mater. Res. A. 111, 1441–1458. https://doi.org/10.1002/jbm.a.37545 (2023).
-
Mohamadali, M., Irani, S., Soleimani, M. & Hosseinzadeh, S. PANi/PAN copolymer as scaffolds for the muscle cell-like differentiation of mesenchymal stem cells. Polym. Adv. Technol. 28, 1078–1087. https://doi.org/10.1002/pat.4000 (2017).
-
Ardeshirylajimi, A., Ghaderian, S. M. H., Omrani, M. D. & Moradi, S. L. Biomimetic scaffold containing PVDF nanofibers with sustained TGF-β release in combination with AT-MSCs for bladder tissue engineering. Gene 676, 195–201. https://doi.org/10.1016/j.gene.2018.07.046 (2018).
-
Awadalla, A. et al. Electrospun nanostructured heparin conjugated-poly-ε-caprolactone based scaffold promote differentiation of smooth muscle cells from adipose mesenchymal stem cells. Process Biochem. 143, 148–162. https://doi.org/10.1016/j.procbio.2024.04.038 (2024).
-
Yang, M. et al. Electrospinning aligned SF/magnetic nanoparticles-blend nanofiber scaffolds for inducing skeletal myoblast alignment and differentiation. ACS Appl. Bio Mater. 7, 7710–7718. https://doi.org/10.1021/acsabm.4c01198 (2024).
-
Hoffman, J., Zheng, S., Zhang, H., Murphy, R. F. & Dahl, K. N. Image-based discrimination of the early stages of mesenchymal stem cell differentiation. Mol. Biol. Cell. 35, ar103. https://doi.org/10.1091/mbc.E24-02-0095 (2024).
-
Gasparotto, M. et al. 3D printed graphene-PLA scaffolds promote cell alignment and differentiation. Int. J. Mol. Sci. 23, 1736 (2022).
-
Han, P., Gomez, G. A., Duda, G. N., Ivanovski, S. & Poh, P. S. P. Scaffold geometry modulation of mechanotransduction and its influence on epigenetics. Acta Biomater. 163, 259–274. https://doi.org/10.1016/j.actbio.2022.01.020 (2023).
-
Guimarães, C. F., Gasperini, L., Marques, A. P. & Reis, R. L. The stiffness of living tissues and its implications for tissue engineering. Nat. Reviews Mater. 5, 351–370. https://doi.org/10.1038/s41578-019-0169-1 (2020).
-
Bonaldi, L. et al. Mechanical characterization of human fascia lata: uniaxial tensile tests from fresh-frozen cadaver samples and constitutive modelling. Bioeng. (Basel). 10 https://doi.org/10.3390/bioengineering10020226 (2023).
-
Sooriyaarachchi, D., Minière, H. J., Maharubin, S. & Tan, G. Z. Hybrid additive microfabrication scaffold incorporated with highly aligned nanofibers for musculoskeletal tissues. Tissue Eng. Regenerative Med. 16, 29–38. https://doi.org/10.1007/s13770-018-0169-z (2019).
-
Choi, J. S., Lee, S. J., Christ, G. J., Atala, A. & Yoo, J. J. The influence of electrospun aligned poly(ɛ-caprolactone)/collagen nanofiber meshes on the formation of self-aligned skeletal muscle myotubes. Biomaterials 29, 2899–2906. https://doi.org/10.1016/j.biomaterials.2008.03.031 (2008).
-
Yeo, M. & Kim, G. Micro/nano-hierarchical scaffold fabricated using a cell electrospinning/3D printing process for co-culturing myoblasts and HUVECs to induce myoblast alignment and differentiation. Acta Biomater. 107, 102–114. https://doi.org/10.1016/j.actbio.2020.02.042 (2020).
Acknowledgements
Porcine mesenchymal stem cells (p-MSCs) were kindly provided by the Cell Factory of the Fondazione IRCCS Policlinico San Matteo (Pavia, Italy), where they were isolated from bone marrow aspirates. The authors gratefully acknowledge the valuable technical support and collaboration of Dr. Patria Comoli, Dr. Maria Antonietta Avanzini, and Dr. Stefania Croce.
Funding
This work was supported by the Italian Ministry of Health, RC-2021-n.986-rcr2021i-24, “3D-hybrid engineered tubular bioscaffold for esophageal tissue regeneration: from in vitro to in vivo validation”.
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Pisani, S., Marconi, S., Mauri, V. et al. Hybrid 3D-printed/electrospun scaffolds drive myogenic differentiation of mesenchymal stem cells (MSCs). Sci Rep (2025). https://doi.org/10.1038/s41598-025-31586-x
-
Received:
-
Accepted:
-
Published:
-
DOI: https://doi.org/10.1038/s41598-025-31586-x
