Preservation of critical quality attributes of mesenchymal stromal cells in 3D bioprinted structures by using natural hydrogel scaffolds
Martorell Cedres, Lluis (Banc de Sang i Teixits. Edifici Dr. Frederic Duran i Jordà)
López-Fernández, Alba (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-Lizarribar, Andrea (Institut de Bioenginyeria de Catalunya)
Sabata, Roger (R&D Human Health. Bioibérica (Barcelona))
Galvez-Martin, Patricia (R&D Human Health. Bioibérica (Barcelona))
Samitier, Josep (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (Barcelona))
Vives Armengol, Joaquim (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2023
Resum:	Three dimensional (3D) bioprinting is an emerging technology that enables complex spatial modeling of cell-based tissue engineering products, whose therapeutic potential in regenerative medicine is enormous. However, its success largely depends on the definition of a bioprintable zone, which is specific for each combination of cell-loaded hydrogels (or bioinks) and scaffolds, matching the mechanical and biological characteristics of the target tissue to be repaired. Therefore proper adjustment of the bioink formulation requires a compromise between: (i) the maintenance of cellular critical quality attributes (CQA) within a defined range of specifications to cell component, and (ii) the mechanical characteristics of the printed tissue to biofabricate. Herein, we investigated the advantages of using natural hydrogel-based bioinks to preserve the most relevant CQA in bone tissue regeneration applications, particularly focusing on cell viability and osteogenic potential of multipotent mesenchymal stromal cells (MSCs) displaying tripotency in vitro, and a phenotypic profile of 99. 9% CD105/CD45, 10. 3% HLA-DR, 100. 0% CD90, and 99. 2% CD73/CD31 expression. Remarkably, hyaluronic acid, fibrin, and gelatin allowed for optimal recovery of viable cells, while preserving MSC's proliferation capacity and osteogenic potency in vitro. This was achieved by providing a 3D structure with a compression module below 8. 8 ± 0. 5 kPa, given that higher values resulted in cell loss by mechanical stress. Beyond the biocompatibility of naturally occurring polymers, our results highlight the enhanced protection on CQA exerted by bioinks of natural origin (preferably HA, gelatin, and fibrin) on MSC, bone marrow during the 3D bioprinting process, reducing shear stress and offering structural support for proliferation and osteogenic differentiation.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-1079 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-719 Ministerio de Economía y Competitividad RD16/0006/0012 Instituto de Salud Carlos III RD21/0017/0022
Nota:	Altres ajuts: acords transformatius de la UAB
Nota:	The authors would like to acknowledge Clara Frago (BST) for their assistance with the assessment of the trilineage differentiation potential of MSC, BM; MicroFabSpace and Microscopy Characterization Facility, Unit 7 of ICTS "NANBIOSIS" from CIBER-BBN at IBEC; and Dr. Màrius Aguirre (VHIR) for facilitating this collaborative work. This work has been developed in the context of AdvanceCat and Base 3D with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014−2020. Research in JV's laboratory is developed in the context of Red Española de Terapias Avanzadas (TERAV, expedient no. RD21/0017/0022) funded by Instituto de Salud Carlos III (ISCIII) in the context of NextGenerationEU's Recovery, Transformation and Resilience Plan. This work was supported by Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008−2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund; CERCA Program and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 719 and 2017 SGR 1079).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Biotechnology and Bioengineering, Vol. 120 Núm. 9 (september 2023) , p. 2717-2724, ISSN 1097-0290

DOI: 10.1002/bit.28381

8 p, 1.4 MB

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