Polymeric reinforcements for cellularized collagen-based vascular wall models: influence of the scaffold architecture on the mechanical and biological properties

Nele Pien; Dalila Di Francesco; Francesco Copes; Michael Bartolf-Kopp; Victor Chausse; Marguerite Meeremans; Marta Pegueroles; Tomasz Jüngst; Catharina De Schauwer; Francesca Boccafoschi; Peter Dubruel; Sandra Van Vlierberghe; Diego Mantovani

doi:10.3389/fbioe.2023.1285565

Polymeric reinforcements for cellularized collagen-based vascular wall models: influence of the scaffold architecture on the mechanical and biological properties

Front Bioeng Biotechnol. 2023 Nov 16:11:1285565. doi: 10.3389/fbioe.2023.1285565. eCollection 2023.

Authors

Affiliations

¹ Laboratory for Biomaterials and Bioengineering, Canada Research Chair Tier I for the Innovation in Surgery, Department of Min-Met-Materials Engineering and Regenerative Medicine, CHU de Quebec Research Center, Laval University, Quebec City, QC, Canada.
² Polymer Chemistry and Biomaterials Group, Centre of Macromolecular Chemistry, Department of Organic and Macromolecular Chemistry, Ghent University, Ghent, Belgium.
³ Faculty of Veterinary Medicine, Department of Translational Physiology, Infectiology and Public Health, Ghent University, Merelbeke, Belgium.
⁴ Laboratory of Human Anatomy, Department of Health Sciences, University of Piemonte Orientale "A. Avogadro", Novara, Italy.
⁵ Department of Functional Materials in Medicine and Dentistry, Institute of Biofabrication and Functional Materials, University of Würzburg and KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), Würzburg, Germany.
⁶ Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya, Barcelona, Spain.

Abstract

A previously developed cellularized collagen-based vascular wall model showed promising results in mimicking the biological properties of a native vessel but lacked appropriate mechanical properties. In this work, we aim to improve this collagen-based model by reinforcing it using a tubular polymeric (reinforcement) scaffold. The polymeric reinforcements were fabricated exploiting commercial poly (ε-caprolactone) (PCL), a polymer already used to fabricate other FDA-approved and commercially available devices serving medical applications, through 1) solution electrospinning (SES), 2) 3D printing (3DP) and 3) melt electrowriting (MEW). The non-reinforced cellularized collagen-based model was used as a reference (COL). The effect of the scaffold's architecture on the resulting mechanical and biological properties of the reinforced collagen-based model were evaluated. SEM imaging showed the differences in scaffolds' architecture (fiber alignment, fiber diameter and pore size) at both the micro- and the macrolevel. The polymeric scaffold led to significantly improved mechanical properties for the reinforced collagen-based model (initial elastic moduli of 382.05 ± 132.01 kPa, 100.59 ± 31.15 kPa and 245.78 ± 33.54 kPa, respectively for SES, 3DP and MEW at day 7 of maturation) compared to the non-reinforced collagen-based model (16.63 ± 5.69 kPa). Moreover, on day 7, the developed collagen gels showed stresses (for strains between 20% and 55%) in the range of [5-15] kPa for COL, [80-350] kPa for SES, [20-70] kPa for 3DP and [100-190] kPa for MEW. In addition to the effect on the resulting mechanical properties, the polymeric tubes' architecture influenced cell behavior, in terms of proliferation and attachment, along with collagen gel compaction and extracellular matrix protein expression. The MEW reinforcement resulted in a collagen gel compaction similar to the COL reference, whereas 3DP and SES led to thinner and longer collagen gels. Overall, it can be concluded that 1) the selected processing technique influences the scaffolds' architecture, which in turn influences the resulting mechanical and biological properties, and 2) the incorporation of a polymeric reinforcement leads to mechanical properties closely matching those of native arteries.

Keywords: 3D printing; cellularized collagen; melt electrowriting; polymeric reinforcement; solution electrospinning; vascular wall model.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. NP would like to acknowledge the financial support of the Research Foundation Flanders (FWO) under the form of a travel grant for her research stay at the ULaval-LBB lab (V429120N). The work of NP was supported by a Natural Science and Engineering Research Council Vanier Canada Graduate Scholarship, and an FWO junior post-doctoral research grant (12E4523N). MM’s work was supported by an FWO SB PhD grant (1S02822N). PD and SV would like to acknowledge the financial support of the FWO under the form of research grants. DM would like to acknowledge the continuous support by the Natural Science and Engineering Research Council of Canada, the contribution of the Fonds de Recherche du Québec sur les Natures et Technologies, and the Canada Foundation for Innovation. MB-K and TJ would like to thank the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation -project number 326998133-TRR 225—subproject B09) for financial support. The authors also appreciate support by the European Union (European Fund for Regional Development—EFRE Bayern, Bio3D-Druck project 20-3400-2-10). Further, TJ acknowledges the European Union for funding via the European Union’s Horizon 2020 research and innovation program under grant agreement 874827.