Soft nanofiber modified micropatterned substrates enhance nativelike endothelium maturation via CXCR4/calcium-mediated actin cytoskeleton assembly

Regeneration and maturation of native-like endothelium is crucial for material-guided small-diameter vascular regeneration.Although parallel-microgroove-patterned(micropatterned)substrates are capable of promoting endothelial regeneration with native-like endothelial cell(EC)alignment,their unbefitting high-stiffness acutely inhibits cell–matrix interaction and endothelial maturation.Given that the sufficient softness of nanofibers allows cells to deform the local matrix architecture to satisfy cell survival and functional requirements,in this study,an effective strategy of decorating micropatterned substrate with soft nanofibers was exploited to enhance cell–matrix interaction for engineering healthy endothelium.Results demonstrated that the micropatterned nanofibrous membranes were successfully obtained with high-resolution parallel microgrooves(groove width:~15μm;groove depth:~5μm)and adequate softness(bulk modulus:2.27±0.18 MPa).This particular substrate markedly accelerated the formation and maturation of confluent native-like endothelium by synchronously increasing cell–cell and cell–matrix interactions.Transcriptome analysis revealed that compared with smooth features,the microgrooved pattern was likely to promote endothelial remodeling via integrinα5-mediated microtubule disassembly and type I interleukin 1 receptormediated signaling pathways,whereas the nanofibrous pattern was likely to guide endothelial regeneration via integrinα5β8-guided actin cytoskeleton remodeling.Nevertheless,endowing micropatterned substrate with soft nanofibers was demonstrated to accelerate endothelial maturation via chemokine(C-X-C motif)receptor 4/calcium-mediated actin cytoskeleton assembly.Furthermore,numerical simulation results of hemodynamics indicated the positive impact of the micropatterned nanofibers on maintaining stable hemodynamics.Summarily,our current work supports an affirmation that the micropatterned nanofibrous substrates can significantly promote regeneration and maturation of native-like endothelium,which provides an innovative method for constructing vascular grafts with functional endothelium.

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.

Application of "Fabulous" stent system to improve aortic remodeling after TEVAR for type B aortic dissection

It is known that the Proximal Extension To Induce Complete Attachment(PETTICOAT)technique improves the distal aortic remodeling compared with standard thoracic endovascular aortic repair(TEVAR).[1,2]However,the only available Zenith Dissection Endovascular System(Cook Medical Inc.,Bloomington,Ind,USA)has several limitations,including only two sizes(36 mm and 46 mm)and an one-taper design,which may not be suitable for the complex morphology of dissection at distal aorta,particular for the east Asian population.Thus,our center designed the new“Fabulous”stent system and acheieved better early curative effect.