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International Journal of Bioprinting Biomimetic scaffolds for tendon healing

cells to recover from the stress process of bioprinting and Conflict of interest
proliferate quickly over time. The cells embedded in the The authors declare no conflicts of interest.
scaffold maintained their phenotype and responded to
the stimuli provided by the developed structure; they Author contributions
also maintained the genetic expression of Scx and Tnc,
while increasing the expression of Fos. The increased Conceptualization: Sandra Ruiz-Alonso, Fátima García-
expression of Col3a1 indicates the activity of embedded Villén, Idoia Gallego, Laura Saenz-Del-Burgo, Jose
tenocytes and their ability to regenerate the extracellular Luis Pedraz
matrix with characteristic biomolecules of the tendon. Data curation: Sandra Ruiz-Alonso, Myriam Sainz-Ramos
The developed scaffolds were also used for the release of Formal analysis: Sandra Ruiz-Alonso, Markel Lafuente-
growth factors that improve the regeneration of tendon Merchan, Myriam Sainz-Ramos
injuries. On the one hand, the release of the factors from Funding acquisition: Laura Saenz-Del-Burgo, Jose L. Pedraz
the scaffold occurs in two phases, namely the fast phase Investigation: Sandra Ruiz-Alonso, Jorge Ordoyo-Pascual,
and the slow phase. PDGF-BB was released more rapidly Markel Lafuente-Merchan, Myriam Sainz-Ramos
at first, as shown by its constant, while VEGF165 was Methodology: Sandra Ruiz-Alonso, Markel Lafuente-
released somewhat more slowly at first. Furthermore, Merchan, Fátima García-Villén, Idoia Gallego
the two factors demonstrated biological activity once Supervision: Idoia Gallego, Laura Saenz-Del-Burgo,
released; VEGF165 caused HUVECs to form a greater Jose L. Pedraz
number of vascular loops with a larger area on days 5 Validation: Jorge Ordoyo-Pascual, Laura Saenz-Del-Burgo
and 9, and PDGF-BB increased the proliferation of Writing – original draft: Sandra Ruiz-Alonso
C2C12 cells. Writing – review & editing: Fátima García-Villén, Idoia
In view of these results, the use of the developed Gallego, Laura Saenz-Del-Burgo, Jose L. Pedraz
biomimetic tissue constructs and scaffolds could lead to an
improved regeneration of partial tendon injuries through Ethics approval and consent to participate
the four selected mechanisms: (i) a more complex and This study had undergone ethical review by the Research
biomimetic combination of biomaterials, (ii) incorporation Ethics Committee for Research with Biological Agents
of tenocytes that produce elements of the ECM and manage and/or Genetically Modified Organisms (CEIAB-UPV/
to regenerate the tissue, (iii) incorporation of VEGF that EHU, BOPV 32, 17/2/2014). The research proposal with
enhances vascularization, thus increasing the supply reference M30_2021_276 was evaluated in accordance
of oxygen and nutrients to the damaged area, and (iv) with ethical considerations. The committee, in its meeting
incorporation of PDGF-BB that promotes cell proliferation held on September 17, 2021 (record 137/2021), granted a
and migration of cells to the damaged area. favorable opinion for the execution of the research project.

Acknowledgments Consent for publication
S.R.-A. thanks the Basque Country Government for the Not applicable.
granted fellowship (PRE_2022_2_0144). The authors wish
to thank the intellectual and technical assistance from Availability of data
the ICTS “NANBIOSIS” more specifically by the Drug The data supporting the findings of this study will be made
Formulation Unit (U10) of the CIBER in Bioengineering, available upon request from the corresponding authors.
Biomaterials, and Nanomedicine (CIBER-BBN) at the
University of the Basque Country (UPV/EHU).
Further disclosure
Funding Part of the entire set of findings had been presented in
national and international congresses:
This project was supported by the Basque Country
Government (Consolidated Groups, IT1448-22) and by (i) Ruiz-Alonso S, Lafuente-Merchan M, Gallego I,
the TriAnkle European project (Horizon 2020 TriAnkle Saenz-Del-Burgo L, Luis Pedraz J. Development of
952981-2). This research was also supported by CIBER- scaffolds based on natural materials for tendon tissue
Consorcio Centro de Investigación Biomédica en Red, regeneration. In: Caraballo I, Casas M, González-
Instituto de Salud Carlos III, Ministerio de Ciencia Rodríguez ML, Rabasco AM, eds. XV Congreso de la
e Innovación. Sociedad Española de Farmacia Industrial y Galénica.

Volume 10 Issue 3 (2024) 463 doi: 10.36922/ijb.2632