Page 308 - IJB-10-6

International

Journal of Bioprinting

RESEARCH ARTICLE
Development and in vitro evaluation of

bioprinted plasma-infused biocarriers
for mesenchymal stromal cell delivery in

musculoskeletal disorder treatment

Cristina Del Amo 1,2† id , Miguel Perez Garrastachu 3† id , Inés Jaúregui 2 id ,
Francisco J. Alvarez 1,4 id , and Isabel Andia *
1,4 id
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
(This article belongs to the Special Issue: Bioprinting of nanomaterials for biomedical applications)

Abstract

A meta-analysis revealed no advantage of surgical over non-surgical treatments,
† These authors contributed equally
to this work emphasizing the need for non-invasive methods, particularly for prevalent
osteoarticular diseases like knee osteoarthritis. To enhance therapeutic efficacy, we
*Corresponding author: developed a plasma-infused gelatin methacryloyl (GelMA) biocarrier loaded with
Isabel Andia
(sabel.andiaortiz@osakidetza.eus) bone marrow-derived mesenchymal stromal cells (BMSCs). These constructs were
evaluated in vitro for their properties and paracrine interactions in non-inflamed
Citation: Del Amo C,
Perez Garrastachu M, Jaúregui I, and inflamed environments. GelMA infused with platelet-rich plasma (PRP) and
J Alvarez F, Andia I. Development fresh frozen plasma (FFP; platelet-poor) were compared. Pristine GelMA was used
and in vitro evaluation of bioprinted as a control. Both PRP and FFP enhanced the proliferation and viability of BMSCs in
plasma-infused biocarriers for
mesenchymal stromal cell biocarriers, promoting cell survival pathways while inhibiting necrotic and apoptotic
delivery in musculoskeletal events. Proteomic analysis displayed no differences in BMSC behavior between
disorder treatment. PRP and FFP in the absence of inflammation (p = 0.550). However, both plasmas
Int J Bioprint. 2024;10(6):4426.
doi: 10.36922/ijb.4426 significantly modified cell behavior under inflammatory conditions (p = 0.001). Both
PRP- and FFP-infused biocarriers activated 10 key signaling pathways, including HIF-
Received: August 2, 2024 1α, neuroinflammation, and extracellular matrix turnover. PRP-specific pathways
Revised: September 10, 2024
Accepted: September 24, 2024 included IL-17, IL-6, and several growth factor signaling pathways. No significant
Published Online: September 24, differences in angiogenesis were linked to platelet dose (p = 0.079), but both PRP
2024 and FFP significantly enhanced angiogenesis compared to GelMA alone (p < 0.001
Copyright: © 2024 Author(s). for PRP; p = 0.002 for FFP). FFP displayed stronger angiogenesis than PRP under IL-1β
This is an Open Access article treatment (p = 0.042). Plasma-infused biocarriers altered BMSC behavior in response
distributed under the terms of the
Creative Commons Attribution to inflammatory cytokines compared to GelMA (p = 0.001). PRP specifically activated
License, permitting distribution, TGF-β signaling under IL-1β (Z = 2.308; p = 1.02E-35), which was not observed
and reproduction in any medium, under TNF-α exposure. These findings suggest that PRP- and FFP-infused biocarriers
provided the original work is
properly cited. may offer promising improvements in regenerative therapies for inflammatory
osteoarticular conditions like knee osteoarthritis.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Extrusion bioprinting; Mesenchymal stromal cells; Platelet-rich plasma;
affiliations. Biocarrier; Musculoskeletal conditions; Osteoarticular pathology

Volume 10 Issue 6 (2024) 300 doi: 10.36922/ijb.4426