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RESEARCH ARTICLE

Induction and real-time ultrasonic monitoring of 3D cartilage-like tissue by a low shear stresses-based bioreactor

Daniel Martínez-Moreno1,2,3,4,5 ,  Antonio Callejas1,4,6 ,  Gema Jiménez1,2,3,4,5 ,  Patricia Gálvez-Martín7 ,  Guillermo Rus1,4,6* ,  Juan Antonio Marchal1,2,3,4,5*
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1 Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Granada, Spain
2 Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain
3 Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
4 Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
5 Biofabrication and 3D (bio)printing (BioFab i3D) laboratory, University of Granada, Granada, Spain
6 Department of Structural Mechanics and Hydraulic Engineering, Faculty of Civil, Canal and Port Engineering, Granada, Spain
7 R&D Human and Animal Health Team, Bioiberica S.A.U., Barcelona, Spain
IJB 2024, 10(4), 3389 https://doi.org/10.36922/ijb.3389
Submitted: 9 April 2024 | Accepted: 9 May 2024 | Published: 12 July 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

Osteoarthritis is a significant socioeconomic illness that mainly affects the articular cartilage, a tissue with a low capacity for self-healing, making it an ideal target for regenerative medicine and tissue engineering. Current interventions to treat cartilage injuries may not be completely effective. In this study, we have developed a novel bioreactor that creates viscous shear stress by flow perfusion. This bioreactor could induce ex vivo maturation of biomimetic 3D cartilage scaffolds, providing a potential solution to this problem. Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were used as a cellular source of the functionalized 3D scaffolds made of 1,4-butanediol thermoplastic polyurethane (bTPUe) modified with pyrene butyric acid (PBA). Our results indicate that our bioreactor induced chondrogenic differentiation, as confirmed by DNA quantification, extracellular matrix determination, and metabolic assay, without any conditioned medium. To control the biomechanical stimulation on IPFP-MSCs, a low-intensity ultrasonic transmission system has been developed and embedded in the bioreactor. Combined with a finite element model (FEM), tissue growth and differentiation can be deconvoluted in real-time from the recorded ultrasonic propagation and interaction across the graft. The FEM reconstructs this complex interaction. This is the first time a low-shear stress-based bioreactor has been reported to not only induce chondrogenic evolution but also monitor it in real time.

Keywords
Scaffolds
Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs)
1 4-Butanediol thermoplastic polyurethane (bTPUe)
Cartilage
Bioreactor
Ultrasounds
Funding
This research was supported by the Ministerio de Economía, Industria y Competitividad (ERDF funds; project no.: RTC-2016-5451-1), Fundación Mutua Madrileña (FMM-AP17196-2019), Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía (ERDF funds; project nos.: B-CTS-230-UGR18, PY18-2470, SOMM17-6109, and P18-FR-2465), Junta de Andalucía- Consejería de Universidad, Investigación e Innovación - Proyecto (P21_00182), the Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, Modeling Nature (MNat; project no.: QUAL21-11), the Instituto de Salud Carlos III (ERDF funds; project nos.: DTS19/00145 and DTS21/00098), the Ministry of Education (grant nos.: EQC2018-004508-P, DPI2017- 83859-R, and UNGR15-CE-3664) and Junta de Andalucía (grant nos.: B-TEP-026-UGR18, IE2017-5537, P18- RT-1653). G.J. received the postdoctoral fellowship from Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020—FEDER funds—Ref: DOC_01574).
Conflict of interest
The authors declare no conflicts of interest
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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