AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.4426
RESEARCH ARTICLE

Development and in vitro evaluation of bioprinted plasma-infused biocarriers for mesenchymal stromal cell delivery in musculoskeletal disorder treatment

Cristina Del Amo1,2 Miguel Perez Garrastachu3 Inés Jaúregui2 Francisco J Alvarez1,4 Isabel Andia1,4*
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1 Regenerative Therapies Unit, Biobizkaia Health Research Institute, Barakaldo, Bizkaia, Spain
2 3D Printing and Bioprinting Lab, Biobizkaia Health Research Institute, Barakaldo, Bizkaia, Spain
3 Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Biscay, Spain
4 Cruces University Hospital, Osakidetza-Basque Health Service and Biobizkaia Health Research Institute, Barakaldo, Bizkaia, Spain
Submitted: 2 August 2024 | Accepted: 24 September 2024 | Published: 24 September 2024
(This article belongs to the Special Issue Bioprinting of Nanomaterials for Biomedical Applications)
© 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/ )
Abstract

A meta-analysis revealed no advantage of surgical over non-surgical treatments, emphasizing the need for non-invasive methods, particularly for prevalent osteoarticular diseases like knee osteoarthritis. To enhance therapeutic efficacy, we developed a plasma-infused gelatin methacryloyl (GelMA) biocarrier loaded with bone marrow-derived mesenchymal stromal cells (BMSCs). These constructs were evaluated in vitro for their properties and paracrine interactions in non-inflamed and inflamed environments. GelMA infused with platelet-rich plasma (PRP) and fresh frozen plasma (FFP; platelet-poor) were compared. Pristine GelMA was used as a control. Both PRP and FFP enhanced the proliferation and viability of BMSCs in biocarriers, promoting cell survival pathways while inhibiting necrotic and apoptotic events. Proteomic analysis displayed no differences in BMSC behavior between PRP and FFP in the absence of inflammation (p = 0.550). However, both plasmas significantly modified cell behavior under inflammatory conditions (p = 0.001). Both PRP- and FFP-infused biocarriers activated 10 key signaling pathways, including HIF- 1α, neuroinflammation, and extracellular matrix turnover. PRP-specific pathways included IL-17, IL-6, and several growth factor signaling pathways. No significant differences in angiogenesis were linked to platelet dose (p = 0.079), but both PRP and FFP significantly enhanced angiogenesis compared to GelMA alone (p < 0.001 for PRP; p = 0.002 for FFP). FFP displayed stronger angiogenesis than PRP under IL-1β treatment (p = 0.042). Plasma-infused biocarriers altered BMSC behavior in response to inflammatory cytokines compared to GelMA (p = 0.001). PRP specifically activated TGF-β signaling under IL-1β (Z = 2.308; p = 1.02E-35), which was not observed under TNF-α exposure. These findings suggest that PRP- and FFP-infused biocarriers may offer promising improvements in regenerative therapies for inflammatory osteoarticular conditions like knee osteoarthritis.  

Keywords
Extrusion bioprinting
Mesenchymal stromal cells
Platelet-rich plasma
Biocarrier
Musculoskeletal conditions
Osteoarticular pathology
Funding
This work was supported by a collaborative fundamental research grant from the Basque Government, Elkartek Program (grant no. BIO4CURE kk-2022-000). Cristina Del Amo and Inés Jaúregui are funded by PT20/00185 from ISCIII, and Miguel Perez-Garrastachu is funded by the post-doctoral fellowship Margarita Salas.
Conflict of interest
The 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