AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025320317
RESEARCH ARTICLE
Early Access

Mixed ultrashort peptide bioinks for improved 3D bioprinting of self-healing trachea-like constructs

Alexander U. Valle-Pérez1,2 Dana Alhattab1,3 Rui Ge1,2 Eter Othman1 Panayiotis Bilalis1 Abdulelah Alrashoudi1 Antonio Cárdenas-Calvario1 Alan Eduardo Avila Ramírez1 Zainab N. Khan1 Manola Moretti1,2 Christian Baumgartner4 Charlotte A.E. Hauser1,2,4*
Received: 7 August 2025 | Accepted: 24 September 2025 | Published online: 6 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Concerns related to the trachea frequently arise from obstructive conditions and occlusions, such as tracheal stenosis, tracheomalacia, traumatic disruptions, and papillary thyroid carcinoma. These medical challenges underscore the need for new biomaterials to support tissue engineering for tissue regeneration. The advent of 3D bioprinting technology has emerged as a pivotal advancement, facilitating the fabrication of patient-specific, biocompatible, cell-laden constructs. This technological advancement enables the controlled promotion of cell growth and tissue development, thereby offering a promising avenue for tissue regeneration. In this study, we developed mixed ultrashort peptide bioinks for three-dimensional (3D) bioprinting of a trachea-like construct that exhibits self-healing and elastic properties. We employed a stiffness prediction map (SPM) as an empirical tool to predict the physical characteristics and stiffness behavior of the mixed bioinks, thereby facilitating the optimization of the 3D bioprinting process. The SPM enabled the fine-tuning of these bioinks by identifying peptide mixtures that successfully mimic the natural stiffness of the perichondral niche microenvironment. These mixed bioinks successfully promoted mesenchymal stromal cell differentiation towards chondrocyte formation, thereby facilitating the biofabrication of elastic 3D-printed structures for trachea regeneration.  Our bioinks exhibited remarkable printing resolution and mechanical properties while supporting cell growth and chondrogenesis. A bioprinted trachea-like model, cultured for up to 100 days, showed excellent mechanical properties, resulting in a stable, yet elastic biomaterial. This study is the first to combine SPM with 3D bioprinting for the fabrication of a trachea-like model, supporting the development of advanced self-healing biomaterials for trachea tissue regeneration.

Keywords
3D bioprinting
Ultrashort peptide bioinks
Trachea-like model
Stiffness prediction map
Self-healing biomaterials
Chondrocytes; Mesenchymal stromal cells
Funding
This research was funded by King Abdullah University of Science and Technology (KAUST). We also thank Graz University of Technology (TU Graz) for additional funding.
Conflict of interest
Charlotte A.E. Hauser serves as the Editorial Board Member of the journal, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. Other authors declare they have no competing interests
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing