Nose to Spine: spheroids generated by human nasal chondrocytes for scaffold-free nucleus pulposus augmentation.

Autor: Gryadunova A; Spine Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland; Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation., Kasamkattil J; Spine Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland., Gay MHP; Spine Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland; Institute of Anatomy, Department of Biomedicine, University of Basel & University Hospital Basel, Pestalozzistrasse 20, 4031, Bael Switzerland., Dasen B; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland., Pelttari K; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland., Mironov V; Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation; Laboratory for Biotechnological Research 3D Bioprinting Solutions, Kashirskoe Highway, 68-2, Moscow, 115409 Russian Federation., Martin I; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland., Schären S; Spine Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland., Barbero A; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland., Krupkova O; Spine Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland; Lepage Research Institute, University of Prešov, 17. Novembra 1, 081 16 Prešov, Slovakia. Electronic address: olga.krupkova@usb.ch., Mehrkens A; Spine Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Biomedicine, University of Basel & University Hospital Basel, Tissue Engineering, ZLF 402, Hebelstrasse 20, 4031 Basel, Switzerland.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2021 Oct 15; Vol. 134, pp. 240-251. Date of Electronic Publication: 2021 Jul 31.
DOI: 10.1016/j.actbio.2021.07.064
Abstrakt: Cell-based strategies for nucleus pulposus (NP) regeneration that adequately support the engraftment and functionality of therapeutic cells are still lacking. This study explores a scaffold-free approach for NP repair, which is based on spheroids derived from human nasal chondrocytes (NC), a resilient cell type with robust cartilage-regenerative capacity. We generated NC spheroids (NCS) in two types of medium (growth or chondrogenic) and analyzed their applicability for NP repair with regard to injectability, biomechanical and biochemical attributes, and integration potential in conditions simulating degenerative disc disease (DDD). NCS engineered in both media were compatible with a typical spinal needle in terms of size (lower than 600µm), shape (roundness greater than 0.8), and injectability (no changes in morphology and catabolic gene expression after passing through the needle). While growth medium ensured stable elastic modulus (E) at 5 kPa, chondrogenic medium time-dependently increased E of NCS, in correlation with gene/protein expression of collagen. Notably, DDD-mimicking conditions did not impair NCS viability nor NCS fusion with NP spheroids simulating degenerated NP in vitro. To assess the feasibility of this approach, NCS were injected into an ex vivo-cultured bovine intervertebral disc (IVD) without damage using a spinal needle. In conclusion, our data indicated that NC cultured as spheroids can be compatible with strategies for minimally invasive NP repair in terms of injectability, tuneability, biomechanical features, and resilience. Future studies will address the capacity of NCS to integrate within degenerated NP under long-term loading conditions. STATEMENT OF SIGNIFICANCE: Current regenerative strategies still do not sufficiently support the engraftment of therapeutic cells in the nucleus pulposus (NP). We present an injectable approach based on spheroids derived from nasal chondrocytes (NC), a resilient cell type with robust cartilage-regenerative capacity. NC spheroids (NCS) generated with their own matrix and demonstrated injectability, tuneability of biomechanical/biochemical attributes, and integration potential in conditions simulating degenerative disc disease. To our knowledge, this is the first study that explored an injectable spheroid-based scaffold-free approach, which showed potential to support the adhesion and viability of therapeutic cells in degenerated NP. The provided information can be of substantial interest to a wide audience, including biomaterial scientists, biomedical engineers, biologists and medical researchers.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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