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Exploring Injectable Scaffolded Spheroids for Nucleus Pulposus Therapy in Degenerated Intervertebral Discs

Title: Exploring Injectable Scaffolded Spheroids for Nucleus Pulposus Therapy in Degenerated Intervertebral Discs
Authors: Vel Balasubramanian, Rathina; Muerner, Marcia; Kopinski-Grünwald, Oliver; Grad, Sibylle; id_orcid:0 000-0001-9552-3653; Fernández-Pérez, Julia; Ovsianikov, Aleksandr
Source: ACS Applied Materials & Interfaces, 18 (7)
Publisher Information: American Chemical Society
Publication Year: 2026
Collection: ETH Zürich Research Collection
Subject Terms: microscaffold; scaffolded spheroids; intervertebral disc degeneration; tissue engineering; high-resolution 3D printing; two-photon polymerization; human bone-marrow derived mesenchymal stem sells
Description: Cell-based therapies for intervertebral disc degeneration (IVDD) treatment face significant challenges, including cell damage from injection-induced shear stress and poor survival in the harsh, nutrient-depleted microenvironment of the intervertebral disc. To overcome these challenges, we developed scaffolded spheroids (S-SPH) by integrating human bone marrow-derived mesenchymal stem cell (hBMSC) spheroids (SPH) into microscaffolds (MS) produced via high-resolution 3D printing, thereby forming injectable tissue-building blocks. We optimized cell seeding density (∼2000 cells/spheroid) and MS fabrication parameters and induced nucleus pulposus (NP)-like differentiation using growth differentiation factor-5 (GDF5) under both normoxic and hypoxic, low-glucose conditions mimicking a healthy in vivo-like environment. S-SPH maintained high cell viability and produced abundant extracellular matrix under both culture conditions. They also upregulated key NP markers, including aggrecan (ACAN), keratin-18 (KRT18), and hypoxia-inducible factor-1α (HIF1α), which indicated successful NP-like differentiation. They also exhibited improved compressive properties approaching those of native human IVD and retained structural integrity and cell viability following injection through a 26G needle. When differentiated into an NP-like phenotype, S-SPH fused and retained a high viability upon injection in vitro. These results demonstrate that S-SPH provide a promising in vitro strategy for NP regeneration, warranting further preclinical evaluation for IVDD therapy. ; ISSN:1944-8244 ; ISSN:1944-8252
Document Type: article in journal/newspaper
File Description: application/application/pdf
Language: English
Relation: https://hdl.handle.net/20.500.11850/796617
DOI: 10.3929/ethz-c-000796617
Availability: https://hdl.handle.net/20.500.11850/796617; https://doi.org/10.3929/ethz-c-000796617
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ ; Creative Commons Attribution 4.0 International
Accession Number: edsbas.2DA70235
Database: BASE