Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration(IVDD).However,the increased levels of reactive oxygen species(ROS)in the degenerated region will impede the efficiency of human adipose-derived stem cells(human ADSCs)transplantation therapy.It inhibits human ADSCs proliferation,and increases human ADSCs apoptosis.Herein,we firstly devised a novel amphiphilic copolymer PEG-PAPO,which could self-assemble into a nanosized micelle and load lipophilic kartogenin(KGN),as a single complex(PAKM).It was an injectable esterase-responsive micelle,and showed controlled release ability of KGN and apocynin(APO).Oxidative stimulation promoted the esterase activity in human ADSCs,which accelerate degradation of esterase-responsive micelle.Compared its monomer,the PAKM micelle possessed better bioactivities,which were attributed to their synergistic effect.It enhanced the viability,autophagic activation(P62,LC3 II),ECM-related transcription factor(SOX9),and ECM(Collagen II,Aggrecan)maintenance in human ADSCs.Furthermore,it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats.Therefore,PAKM micelles perform promoting cell survival and differentiation effects,and may be a potential therapeutic agent for IVDD.

A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

The current effective method for treatment of spinal cord injury(SCI)is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells(NSCs)to repair SCI.However,the method is characterized by several challenges including irregular wounds,and mechanical and electrical mismatch of the material-tissue interface.In the current study,a unique and facile agarose/gelatin/polypyrrole(Aga/Gel/PPy,AGP3)hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy.The gelation occurred through non-covalent interactions,and the physically crosslinked features made the AGP3 hydrogels injectable.In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility,and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes.The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas.In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation,resulting in significant functional recovery.RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+signaling cascades.Overall,this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.