Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway

Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and inherent function of the disc.The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD.We synthesized biocompatible layered double hydroxide(LDH)nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining,qPCR,and immunofluorescence analyses.LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model.Repair and regeneration evaluated using X-ray,magnetic resonance imaging,and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure.Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix(ECM)and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration.The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.