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Decellularized nucleus pulposus matrix/chitosan hybrid hydrogel combined with nucleus pulposus stem cells and GDF5-loaded microspheres for intervertebral disc degeneration prevention

作者:Tao Ma, Chen Liu, Quanlai Zhao, Yu Zhang, Xiao Liang · 发表于:Molecular Medicine · 年份:2024 · DOI:10.1186/s10020-024-00777-z · 被引用次数:26 · 研究领域:Spine and Intervertebral Disc Pathology、Periodontal Regeneration and Treatments、Tendon Structure and Treatment

BACKGROUND: Intervertebral disc degeneration (IDD) is considered an important pathological basis for spinal degenerative diseases. Tissue engineering is a powerful therapeutic strategy that can effectively restore the normal biological properties of disc units. In this study, hydrogels loaded with growth/differentiation factor 5 (GDF5) and stem cells were combined to provide an effective strategy for nucleus pulposus regeneration. METHODS: Nucleus pulposus stem cells (NPSCs) were obtained by low-density inoculation and culture, and their stem cell characteristics were verified by flow cytometry and a tri-lineage-induced differentiation experiment. A decellularized nucleus pulposus matrix (DNPM) and chitosan hybrid hydrogel was prepared, and GDF5-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were incorporated into the hydrogels to obtain a composite hydrogels with GDF5-loaded microspheres. Taking bone marrow mesenchymal stem cells (BMSCs) as a reference, the effect of composite hydrogels with GDF5-loaded microspheres on the chondrogenic differentiation of NPSCs was evaluated. A model of intervertebral disc degeneration induced by acupuncture on the tail of rats was constructed, and the repair effect of composite hydrogels with GDF5-loaded microspheres combined with NPSCs on IDD was observed. RESULTS: Stem cell phenotype identification, stemness gene expression and tri-lineage-induced differentiation confirmed that NPSCs had characteristics similar to those of BMSCs....