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International Journal of Bioprinting Stretchable scaffold for modeling fibrosis
in fibrosis, compared to scaffolds under static conditions. Software: Mattia Spedicati, Francesca Tivano, Janira Bei,
In particular, stimulated cells had increased expressions Mario Lavella
of the α-SMA and fibronectin and decreased expression Supervision: Irene Carmagnola, Valeria Chiono
of collagen III. These results supported the hypothesis Validation: Mattia Spedicati, Francesca Tivano, Janira Bei,
48
that the application of cyclic mechanical stimulations Mario Lavella, Alice Zoso
to cellularized bioartificial scaffolds may trigger HCF Writing – original draft: Mattia Spedicati, Francesca Tivano
activation into myofibroblasts. Deeper investigations Writing – review & editing: Mario Lavella, Alice Zoso, Irene
through protein and gene expression quantifications (e.g., Carmagnola, Valeria Chiono
qPCR) are warranted to validate the effect of mechanical
stimulation on HCF phenotype and culture time. This Ethics approval and consent to participate
system would allow us to better understand and manage Not applicable.
fibrosis onset by tuning stretch timing and rate.
In summation, the mechanical and biological properties Consent for publication
of bioartificial PCL/GelMA scaffolds make them a Not applicable.
promising platform with in vivo-like mechanical properties,
tailored by PCL scaffold architecture and GelMA hydrogel Availability of data
concentration, for the development of dynamic in vitro
models of human cardiac fibrotic tissues. Further validation Data are available from the corresponding author upon
will allow their use for the in vitro preclinical testing of reasonable request.
medical devices and advanced therapies.
References
Acknowledgments
1. World Health Organization (WHO). Cardiovascular
The authors would like to acknowledge CellScale (Canada) Diseases (CVDs).
for kindly lending us the MechanoCulture T6 bioreactor https://www.Who.Int/En/News-Room/Fact-Sheets/Detail/
and especially Johannes de Bondt (Business Unit Manager, Cardiovascular-Diseases-(Cvds); 2019.
Germany at World Precision Instruments - Europe) for 2. Talman V, Ruskoaho H. Cardiac fibrosis in myocardial
his support. infarction—from repair and remodeling to regeneration.
Cell Tissue Res. 2016;365(3):563-581.
Funding doi: 10.1007/s00441-016-2431-9
This work was supported by the European Research 3. Woodruff MA, Hutmacher DW. The return of a forgotten
Council (ERC) under the European Union’s Horizon 2020 polymer – polycaprolactone in the 21st century. Prog Polym
research and innovation funding program (BIORECAR; Sci. 2010;35(10):1217-1256.
Grant Agreement No. 772168). doi: 10.1021/acsami.3c04362
4. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S,
Conflict of interest Khademhosseini A. Cell-laden microengineered gelatin
methacrylate hydrogels. Biomaterials. 2010;31(21):5536-5544.
The authors declare no conflicts of interest. doi: 10.1016/j.biomaterials.2010.03.064
Author contributions 5. Deddens JC, Sadeghi AH, Hjortnaes J, et al. Modeling the
human scarred heart in vitro: toward new tissue engineered
Conceptualization: Irene Carmagnola, Valeria Chiono models. Adv Healthc Mater. 2017;6(3):1-21.
Data curation: Mattia Spedicati, Francesca Tivano, Janira doi: 10.1002/adhm.201600571
Bei, Mario Lavella, Alice Zoso 6. Olvera D, Sohrabi Molina M, Hendy G, Monaghan MG.
Formal analysis: Mattia Spedicati, Francesca Tivano, Janira Electroconductive melt electrowritten patches matching the
Bei, Mario Lavella mechanical anisotropy of human myocardium. Adv Funct
Funding acquisition: Valeria Chiono Mater. 2020;30(44):1-10.
Investigation: Mattia Spedicati, Francesca Tivano, Janira doi: 10.1002/adfm.201909880
Bei, Mario Lavella, Alice Zoso 7. Castilho M, van Mil A, Maher M, et al. Melt electrowriting
Methodology: Mattia Spedicati, Francesca Tivano, Janira allows tailored microstructural and mechanical design of
Bei, Mario Lavella, Alice Zoso scaffolds to advance functional human myocardial tissue
Project administration: Valeria Chiono formation. Adv Funct Mater. 2018;28(40):1-10.
Resources: Valeria Chiono doi: 10.1002/adfm.201803151.
Volume 10 Issue 3 (2024) 486 doi: 10.36922/ijb.2247

