For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
Zheng XingChen ZhaoChunchen ZhangYubo FanHaifeng Liu
A significant limitation in the engineering of artificial small-diameter vascular scaffolds is that the number of endothelial cells(ECs)is not sufficient to generate a confluent coverage of the vascular scaffolds,so that the surfaces of vascular scaffolds form thrombus via platelet adhesion and aggregation.Thrombus decrease relies on three-dimensional(3D)scaffolds to mimic the natural extracellular matrix(ECM)as templates to regulate cell behavior and facilitate tissue maturation.Here,we developed 3D scaffolds consisting of silk fibroin(SF)nanofibers and homogeneous microspheres by electrospinning and microfluidics.The nanofibers with diameters ranging from 250 to 350 nm doped with microspheres(2–10μm)formed bridge-shaped structures.ECs were seeded and maintained on the 3D microsphere-nanofiber scaffolds with a mean fiber diameter of 300 nm.A 10%higher ratio of cell proliferation on 3D microsphere-nanofiber SF scaffolds was noted as compared to that on microporous and sponge-like SF scaffolds with small surface network fabricated by freeze-drying.Moreover,the gene transcript levels including CD146,VE-C and PECAM-1 were better preserved on 3D microsphere-nanofiber SF scaffolds than those on freeze-dried scaffolds.Thus,the developed 3D microsphere-nanofiber structure may have a myriad of applications in vascular tissue engineering scaffolds and cardiovascular devices.
Qiang LiuGuoliang YingNan JiangAli KYetisenDanyu YaoXiaoying XieYubo FanHaifeng Liu
Cell sheet engineering has been proven to be a promising strategy for cardiac remodeling post-myocardial infarction. However, insufficient mechanical strength and low cell retention lead to limited therapeutic efficiency. The thickness and area of artificial cardiac patches also affect their therapeutic efficiency. Cardiac patches prepared by combining cell sheets with electrospun nanofibers, which can be transplanted and sutured to the surface of the infarcted heart, promise to solve this problem. Here, we fabricated a novel cardiac patch by stacking brown adipose-derived stem cells (BADSCs) sheet layer by layer, and then they were combined with multi-walled carbon nanotubes (CNTs)-containing electrospun polycaprolactone/silk fibroin nanofibers (CPSN). The results demonstrated that BADSCs tended to generate myocardium-like structures seeded on CPSN. Compared with BADSCs suspension-containing electrospun nanofibers, the transplantation of the CPSN-BADSCs sheets (CNBS) cardiac patches exhibited accelerated angiogenesis and decreased inflammation in a rat myocardial infarction model. In addition, the CNBS cardiac patches could regulate macrophage polarization and promote gap junction remodeling, thus restoring cardiac functions. Overall, the hybrid cardiac patches made of electrospun nanofibers and cell sheets provide a novel solution to cardiac remodeling after ischemic myocardial infarction.
Xinbo WeiLi WangCuimi DuanKai ChenXia LiXimin GuoPeng ChenHaifeng LiuYubo Fan
Immediate loading(IL)increases the risk of marginal bone loss.The present study investigated the biomechanical response of peri-implant bone in rabbits after IL,aiming at optimizing load management.Ninety-six implants were installed bilaterally into femurs of 48 rabbits.Test implants on the left side created the maximal initial stress of 6.9 and 13.4 MPa in peri-implant bone and unloaded implants on the contralateral side were controls.Bone morphology and bone-implant interface strength were measured with histological examination and push-out testing during a 12-week observation period.Additionally,the animal data were incorporated into finite element(FE)models to calculate the bone stress distribution at different levels of osseointegration.Results showed that the stress was concentrated in the bone margin and the bone stress gradually decreased as osseointegration proceeded.A stress of about 2.0 MPa in peri-implant bone had a positive effect on new bone formation,osseointegration and bone-implant interface strength.Bone loss was observed in some specimens with stress exceeding 4.0 MPa.Data indicate that IL significantly increases bone stress during the early postoperative period,but the load-bearing capacity of peri-implant bone increases rapidly with an increase of bone-implant contact.Favorable bone responses may be continually promoted when the stress in peri-implant bone is maintained at a definite level.Accordingly,the progressive loading mode is recommended for IL implants.
