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.

Augmenting osteoporotic bone regeneration through a hydrogel-based rejuvenating microenvironment

Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery.The hydrogel,named GelHFS,was created through host-guest polymerization of gelatin and acrylatedβ-cyclodextrin.Incorporation of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche.Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion pathway.Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone strength.Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect.These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.