AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.4566
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RESEARCH ARTICLE

Collagen bioinks redefined: Optimizing ionic strength and growth factor delivery for cartilage tissue engineering

Murad Redzheb1* ,  Yordan Sbirkov2,3 ,  Atanas Valev1 ,  Vasil Dzharov3 ,  Hristi Petrova1 ,  Tatyana Damyanova2 ,  Ani Georgieva1,4 ,  Victoria Sarafian2,3
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1 MatriChem Ltd., Sofia, Bulgaria
2 Department of Medical Biology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria
3 Department of Molecular and Regenerative Medicine, Research Institute at Medical University of Plovdiv (RIMU-Plovdiv), Plovdiv, Bulgaria
4 Section Pathology, Institute of Experimental Morphology, Pathology and Anthropology with Museumn Academy of Sciences, Sofia, Bulgaria
IJB, 4566 https://doi.org/10.36922/ijb.4566
Submitted: 18 August 2024 | Accepted: 29 September 2024 | Published: 30 September 2024
© 2024 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/ )
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Abstract

Tissue engineering of hyaline cartilage for regenerative medicine and the treatment of osteoarthritis has advanced significantly over the past decade, driven by developments in 3D bioprinting and biomaterials science. Despite these advances, standardized biofabrication protocols approved for clinical applications remain elusive, underscoring the need for research into widely accessible, non-immunogenic, and biocompatible bioinks that support chondrogenesis. This study proposes a strategy to improve the gelation kinetics of collagen bioinks by fine-tuning their ionic strength and reports a highly efficient sequestration of TGF-β1 within them, alongside their compatibility with bioprinting live chondrocytes and adipose-derived stem cells for cartilage tissue engineering. By adjusting sodium chloride and phosphate-buffered saline (PBS) concentrations, we demonstrate that reduced ionic strengths accelerate gelation, facilitating high-fidelity bioprinting while supporting high cell viability and proliferation. Furthermore, at 1% collagen concentration, the hydrogel effectively immobilized TGF-β1, with less than 0.5% released over two weeks, indicating potent sequestration capability. Using adipose-derived mesenchymal stromal cells, histomorphological and transcriptomic analyses reveal that the presence of TGF-β1 significantly enhances chondrogenesis. These results underscore the neglected role of ionic strength in optimizing collagen ink properties for advanced bioprinting applications and highlight the potential of collagen hydrogels as effective carriers for sustained growth factor delivery, paving the way for successful cartilage tissue engineering strategies.

Keywords
Collagen
Bioink
Bioprinting
Cartilage
Chondrocytes
Gelation kinetics
TGF-β1
Funding
This work was supported by the Bulgarian National Innovation Fund (grant number: 13IF-02-9/07.12.2022).
Conflict of interest
The authors declared the following potential conflicts of interest concerning the research, authorship, and/or publication of this article: M.R. is the majority owner and Managing Director of MatriChem, Ltd., which markets the collagen used in this study. A.V., H.P., and A.G. are MatriChem employees. No conflicts of interest concerning the research, authorship, and/or publications exist for all other authors.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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