Regulation of the macrophage-related inflammatory microenvironment for atherosclerosis treatment and angiogenesis via anti-cytokine agents

Macrophages-mediated atherosclerosis(AS)is an inflammatory disease and the most common cause of ischemia.With the progress of basic and clinical research,anti-cytokine therapy has garnered considerable attention of the research community for the regulation of the inflammatory microenvironment for AS treatment.Despite of their promising potential,primary clinical trials have revealed that anti-cytokine drugs exhibit poor selectivity and thus affect other parts of the immune system,especially during long-term management.To circumvent these limitations,herein we exploited mesoporous silica nanoparticles(MSNs)with a pore size of 15.5 nm as carriers for the anti-interleukin-1β(anti-IL-1β)delivery to be the anti-cytokine agents.In vitro mechanistic studies indicated that the MSNs@anti-IL-1βcan regulate the macrophage-related inflammatory microenvironment,promote the viability of vascular endothelial cells(vECs),and reduce proliferation and phenotypic switching of vascular smooth muscle cells(vSMCs).In vivo evaluation further revealed that the MSNs@anti-IL-1βwere preferentially accumulated in macrophages,impeding the AS progress by maintaining the endothelium integrity and inhibiting the vSMCs proliferation.Besides,MSNs@antiIL-1βinduced neovascularization and improved hindlimb ischemia regeneration.Taken together,these MSNs affording the sustained release of anti-cytokine agents may have broad implications for the clinical management of the AS,including the reduction of the AS progression and alleviation of the ischemia.

Graphene foam/hydrogel scaffolds for regeneration of peripheral nerve using ADSCs in a diabetic mouse model

The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(ADSCs)are promising candidates for treatment of DPNI due to their abundant source,excellent differentiation and paracrine ability.Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells,and tube formation.Mechanistically,ADSCs could regulate Nrf2/HO-1,NF-κB and PI3K/AKT/mTOR signaling pathways,showing multiple functions in reducing oxidative stress and inflammation,and regulating cell metabolism,growth,survival,proliferation,angiogenesis,differentiation of Schwann cell and myelin formation.In current study,novel graphene foam(GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI.GF/hydrogel scaffold exhibited excellent mechanical strength,suitable porous network,superior electrical conductivity,and good biocompatibility.In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells.Moreover,in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles,thus providing a novel and attractive therapeutic approach for DPNI patients.