Electrospun compliant heparinized elastic vascular graft for improving the patency after implantation.

The low patency rate after artificial blood vessel replacement is mainly due to the ineffective use of anticoagulant factors and the mismatch of mechanical compliance after transplantation. Electrospun nanofibers with biomimetic extracellular matrix three-dimensional structure and tunable mechanical strength are excellent carriers for heparin. In this work, we have designed and synthesized a series of biodegradable poly(ester-ether-urethane)ureas (BEPU), following compound with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid BEPU/heparin nanofibers tubular graft for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The results in vitro demonstrated that the electrospun L-PEUUH (LDI-based PEUU with heparin) vascular graft was of regular microstructure, optimum surface wettability, matched mechanical properties, reliable cytocompatibility, and strongest endothelialization in situ. Replacement of resected abdominal artery with the L-PEUUH vascular graft in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), as well as stabilizing the blood microenvironment. This research demonstrates the L-PEUUH vascular graft with substantial patency, indicating their potential for injured vascular healing.

Evaluation of electrospun PCL diol-based elastomer fibers as a beneficial matrix for vascular tissue engineering.

The main reason for the failure of artificial blood vessel transplantation is the lack of mechanically matched materials with excellent blood compatibility. The electrospun biodegradable polyurethane (BPU) fibers with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM) is one of the most suitable options for vascular graft. In our recent study, we prepared a series of PCL-based BPU fibers by combining two-step solution polymerization and electrospinning. SEM, 1H NMR, ATR-FTIR, XRD, TG, water contact angle, and mechanical tests were used to analyze the chemical structure, microstructure, thermal properties, surface wettability, degradation, cytocompatibility, and hemocompatibility in vitro of electrospun fibers. The results show that the synthesized H-PEUU, L-PEUU, H-PEEUU, and L-PEEUU have different crystalline properties, thus exhibiting distinctive thermal, mechanical, and degradation properties. Although the existence of the molecular structure of LDI and PEG600 in fibers can promote cell proliferation and migration unilaterally, the microstructure of the material is also the main factor affecting the biocompatibility of cells. The results suggest that the designed PCL-based degradable polyurethane electrospun fiber is expected to be applied to vascular tissue engineering.

Electrospun PCL/collagen hybrid nanofibrous tubular graft based on post-network bond processing for vascular substitute.

Inhibiting thrombus formation and intimal hyperplasia is essential for orthotopic tissue-engineered vascular grafts. The matching mechanical properties of autologous blood vessels and inhibition of platelet aggregation are considered as two points to improve the success rate of transplantation. The poly(ε-caprolactone)/collagen/heparin composite vascular graft (PCLHC) with three-dimensional network structure were constructed by electrospinning, which can mimic natural vascular biomechanics and enhance the viability of cells viability in vitro. The hybrid collagen matrix network nanofibers formed by electrospinning exhibited uniform and smooth morphology. The results of mechanical experiments showed that PCLHC had similar mechanical properties to natural blood vessels. And the addition of heparin enhanced the anticoagulation of PCLHC. Simultaneous three-component hybrid nanofibers showed a potentially reliable ability to promote the proliferation of human umbilical vein endothelial cells (HUVECs). In summary, all the results showed that the three-dimensional network structure of PCLHC presented the potential to heal injured vessels.

Construction and performance evaluation of Hep/silk-PLCL composite nanofiber small-caliber artificial blood vessel graft.

To meet the growing clinical demand for small-caliber blood vessel grafts to treat cardiovascular diseases, it is necessary to develop safe and long-term unobstructed grafts. In this study, a biodegradable graft made of composite nanofibers is introduced. A composite nanofiber core-shell structure was prepared by a combination of conjugate electrospinning and freeze-dry technology. The core fiber was poly(l-lactide-co-caprolactone) (PLCL)-based and the core fibers were coated with heparin/silk gel, which acted as a shell layer. This special structure in which the core layer was made of synthetic materials and the shell layer was made of natural materials took advantage of these two different materials. The core PLCL nanofibers provided mechanical support during vascular reconstruction, and the shell heparin/silk gel layer enhanced the biocompatibility of the grafts. Moreover, the release of heparin in the early stage after transplantation could regulate the microenvironment and inhibit the proliferation of intima. All of the graft materials were biodegradable and safe biomaterials, and the degradation of the graft provided space for the growth of regenerated tissue in the late stage of transplantation. Animal experiments showed that the graft remained unobstructed for more than eight months in vivo. In addition, the regenerated vascular tissue provided a similar function to that of autogenous vascular tissue when the graft was highly degraded. Thus, the proposed method produced a graft that could maintain long-term patency in vivo and remodel vascular tissue successfully.

Electrospun Bilayer Composite Vascular Graft with an Inner Layer Modified by Polyethylene Glycol and Haparin to Regenerate the Blood Vessel.

In this study, we prepared a composite vascular graft with two layers. The inner layer, which was comprised of degradable Poly(lactic-co-glycolic acid) (PLGA)/Collagen (PC) nanofibers modified by mesoporous silica nanoparticles (MSN), was grafted with polyethylene glycol (PEG) and heparin to promote cell proliferation and to improve blood compatibility. The outer layer was comprised of polyurethane (PU) nanofibers in order to provide mechanical support. The growth and proliferation of human umbilical vein endothelial cells (HUVECs) in the inner layer was significant, and blood compatibility testing showed that the inner layer had good blood compatibility. The MSN-PEG-Heparin on the fiber surface was observed in vitro during the degradation of the inner layer. After 60 days, the weight of fiber membrane decreased by 92.4%. The inner layer did not cause an inflammatory reaction during the degradation process in vivo and there was uniform cellular growth on the PC/MSN-PEG-Heparin fiber membrane. Composite grafts implanted into the rabbit carotid artery were evaluated for 8 weeks by H&E and immunohistochemical staining, demonstrating that a monolayer of endothelium (CD31-labeled) and smooth muscle (αSMA-labeled) regenerated on the composite graft. Our results demonstrate that the composite graft, with a functional inner layer, has potential to be used for small-caliber blood vessels with long-term patency.

Delivery of alginate-chitosan hydrogel promotes endogenous repair and preserves cardiac function in rats with myocardial infarction.

The regenerative potential of alginate-chitosan composite in bone and cartilage tissue has been well documented, but its potential utility in cardiac tissue engineering has remained unknown. This study sought to determine whether early intramyocardial injection of alginate-chitosan could prevent left ventricular (LV) remodeling after myocardial infarction (MI), leading to a more favorable course of tissue restoration. In a rat model of acute MI, local injection of alginate-chitosan hydrogel into the peri-infarct zone preserved scar thickness, attenuated infarct expansion, and reduced scar fibrosis after 8 weeks, concomitantly with promoting increased angiogenesis and greater recruitment of endogenous repair at the infarct zone. Furthermore, this treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry. The cardiac function of the control-injected animals deteriorated over the 8-week course, while that of the hydrogel-injected animals did not.In addition, the hydrogel did not exacerbate inflammation in the heart. Intramyocardial injection of alginate-chitosan hydrogel represents a useful strategy to treat MI. It demonstrated marked therapeutic efficacies on various tissue levels after extensive MI, as well as potential to induce endogenous cardiomyocyte proliferation and recruit cardiac stem cells.

Synthetic ePTFE grafts coated with an anti-CD133 antibody-functionalized heparin/collagen multilayer with rapid in vivo endothelialization properties.

An anti-CD133 antibody multilayer functionalized by heparin/collagen on an expanded polytetrafluoroethylene (ePTFE) graft was developed to accelerate early endothelialization. The surface modification of ePTFE grafts demonstrated that the multilayer is stable in static incubation and shaking conditions and that the anti-CD133 antibodies were successfully cross-linked onto the surface. Blood compatibility tests revealed that the coimmobilized heparin/collagen films in the presence or absence of anti-CD133 antibodies prolonged the blood coagulation time and that there was less platelet activation and aggregation, whereas the hemolysis rate was comparable with the bare ePTFE grafts. Cellular proliferation was not inhibited, as the heparin/collagen synthetic vascular grafts coated with CD133 antibody showed little cytotoxicity. The endothelial cells adhered well to the modified ePTFE grafts during a cell adhesion assay. A porcine carotid artery transplantation model was used to evaluate the modified ePTFE grafts in vivo. The results of histopathological staining and scanning electron microscopy indicated that the anti-CD133 antibody was able to accelerate the attachment of vascular endothelial cells onto the ePTFE grafts, resulting in early rapid endothelialization. The success of the anti-CD133 antibody-functionalized heparin/collagen multilayer will provide an effective selection system for the surface modification of synthetic vascular grafts and improve their use in clinical applications.