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.
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.
Acta Biomater. 2021 Oct 15;134:240-251. doi: 10.1016/j.actbio.2021.07.064. Epub 2021 Jul 31.
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.
目前的再生策略仍然不能充分支持治疗细胞在髓核（NP）中的植入。我们提出了一种基于鼻软骨细胞（NC）球体的可注射方法，NC 是一种具有强大软骨再生能力的弹性细胞类型。我们用自身基质生成的 NC 球体（NCS）表现出了可注射性、生物力学/生化特性的可调节性，以及在模拟退行性椎间盘疾病（DDD）条件下的整合潜力。据我们所知，这是第一项探索可注射球体无支架方法的研究，该方法显示出在退行性 NP 中支持治疗细胞黏附和存活的潜力。所提供的信息可能对广泛的受众具有重要意义，包括生物材料科学家、生物医学工程师、生物学家和医学研究人员。
