Yunhui Zhao

Dual-delivery of VEGF and PDGF by double-layered electrospun membranes for blood vessel regeneration.

Tissue engineering of small-diameter blood vessels is still challenging because of restenosis and burst. To prevent thrombosis, rapid endothelialization along the lumen of grafts is intended, followed by proliferation of vascular smooth muscle cells (VSMCs) around the exterior for compliance. To this goal, two modified coaxial electrospinning techniques were developed to encapsulate vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGF), respectively, to regulate proliferation of vascular endothelial cells (VECs) and VSMCs. Release profiles, in vitro cell proliferation and in vivo implantation of double-layered electrospun membranes were investigated, and what made it special was the electrospun membranes were composed of chitosan hydrogel/poly(ethylene glycol)-b-poly(L-lactide-co-caprolactone) (PELCL) electrospun membrane loaded with VEGF as the inner layer and emulsion/PELCL electrospun membrane-loaded PDGF as the outer. It was found that dual-release of VEGF and PDGF could accelerate VEC proliferation in the first 6 days, and modulate slow VSMC proliferation in the initial 3 days whereas generate rapid proliferation after day 6, which is of great benefit to blood vessel regeneration. Four weeks of in vivo replacement of rabbit carotid artery demonstrated that VECs and VSMCs developed on the lumen and exterior of vascular grafts, respectively, and no thrombus or burst appeared. It was concluded that dual-delivery of VEGF and PDGF by the modified electrospun membranes could facilitate revascularization.

Performance of a multilayered small-diameter vascular scaffold dual-loaded with VEGF and PDGF

The urgent needs of functional arterial replacements for curing the vascular system diseases have been proposed for many years. However, an ideal small-diameter vascular scaffold, which is nonthrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of natural vessels, and supports neovascular tissue reconstruction, is still in progress. For this purpose, we previously attempted dual-delivery of VEGF and PDGF by double-layered electrospun membranes. Here, a multilayered vascular scaffold in 1.5-mm diameter with sufficient mechanical properties was developed by electrospinning from poly(ethylene glycol)-b-poly(L-lactide-co-ε-caprolactone) (PELCL), poly(L-lactide-co-glycolide) (PLGA), poly(ε-caprolactone) (PCL) and gelatin. Spatio-temporal releases of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGF) were specially controlled by the inner PELCL and middle PLGA layers, respectively, and the outer PCL layer contributed to the mechanical stability. Introduction of gelatin improved vascular endothelial cells adhesion at first, and loosen membrane after its degradation facilitated vascular smooth muscle cells (VSMCs) ingrowth. Cell activities indicated dual release of growth factors promoted endothelialization and inhibited VSMCs hyperproliferation. The small-diameter vascular scaffold dual-loading VEGF and PDGF could maintain patency in rabbit left common carotid artery for 8 weeks. It is concluded that the specially prepared fibrous scaffold in multilayer could benefit blood vessel reconstruction.

Facile preparation of superhydrophobic coating by spraying a fluorinated acrylic random copolymer micelle solution

A superhydrophobic polymer coating is prepared by spraying a fluorinated acrylic random copolymer micelle solution. The surface morphology of the coating can be controlled by the solvent, and the possible formation mechanism of the superhydrophobic coating is proposed. The coating displays anti-icing properties and resistance to low temperature.

A pilot study of conically graded chitosan–gelatin hydrogel/PLGA scaffold with dual‐delivery of TGF‐β1 and BMP‐2 for regeneration of cartilage–bone interface

Repair of cartilage-bone interface tissue remains challenging, because it combines different cell types and gradients of composition and properties. To enable simultaneous regeneration of bone, cartilage, and especially their interface, a conically graded scaffold of chitosan-gelatin hydrogel/poly(l-lactide-co-glycolide) (PLGA) was facilely prepared in the study. The chitosan-gelatin hydrogel containing transforming growth factor β1 (TGF-β1) was used for chondrogenesis, while the PLGA scaffold loading bone morphogenetic protein-2 (BMP-2) for osteogenesis. The conically graded transition from the hydrogel to PLGA scaffold and graded variation in amount of growth factors from TGF-β1 to BMP-2 benefited the cartilage-bone interface reconstruction. The graded scaffold exhibited spatio-temporal delivery of TGF-β1 and BMP-2. Preliminary results of in vitro cell culture demonstrated that the hydrogel and PLGA phases could promote bone marrow mesenchymal stem cells toward chondrogenic and osteogenic differentiation, respectively. From the result of the pilot in vivo experiment, it showed that the regenerated hyaline-like cartilage surface and subchondral bone excellently integrated with the native tissues were found by using the TGF-β1 and BMP-2 double-loaded hydrogel/PLGA graded scaffold via H&E and immunohistochemical stainings of collagen I, collagen II, and osteocalcin at 2 months. The obtained preliminary experiment results showed that the hydrogel/PLGA graded scaffold combining multiphasic composition and spatial dual growth-factor delivery would be useful for cartilage-bone interface tissue defect repair.

Effect of Cyclic Loading on In Vitro Degradation of Poly(L-lactide-co-glycolide) Scaffolds

The in vitro degradation performance of porous scaffolds is very important in tissue engineering, especially the scaffold implanted in the environment imitating the repaired tissue. In this paper, the effect of cyclic loading on in vitro degradation of porous poly(L-lactide-co-glycolide) (PLGA) scaffolds was studied by incubating the samples in phosphate-buffered saline at 37°C and pH 7.4 under dynamic conditions (cyclic loading) and static conditions (shaking water bath) for 12 weeks. The results showed earlier morphological variations and faster reduction in mass, dimensions and relative molecular mass of the scaffolds under dynamic conditions. Mechanical properties (the compressive modulus and the compressive strength) of the PLGA scaffolds under both conditions tended to increase in the first 3 weeks, but showed a decrease tendency afterward. The scaffolds under dynamic conditions were too brittle to be further characterized after degradation for 6 weeks, while those under static conditions endured degradation until week 8. The degradation mechanism of the PLGA scaffolds under cyclic loading was clearly explained and a three-stage degradation model based on the degradation behaviors of the scaffolds under two conditions was presented.

Controllable dual-release of dexamethasone and bovine serum albumin from PLGA/β-tricalcium phosphate composite scaffolds

Localized dual-drug delivery from biodegradable scaffolds is an important strategy in tissue engineering. In this study, porous poly(L-lactide-co-glycolide) (PLGA)/β-tricalcium phosphate scaffolds containing both dexamethasone (Dex) and bovine serum albumin (BSA) were prepared by incorporating Dex-loaded and BSA-loaded microspheres into the scaffolds. PLGA microspheres containing Dex or BSA were prepared by spray-drying and double emulsion/solvent evaporation, respectively. In vitro release studies indicated that microspheres prepared from PLGA in 3:1 molar ratio of L-lactide/glycolide and 89.5 kDa relative molecular mass showed prolonged release profiles compared with those prepared from PLGA in 1:1 L-lactide/glycolide molar ratio and 30.5 kDa relative molecular mass. Additionally, introduction of poly(ethylene glycol) in the PLGA chain could improve the encapsulation efficiency and reduce the release rate. Based on the above results, controllable dual-release of Dex and BSA with relatively higher or lower release rate was achieved by incorporating Dex-loaded and BSA-loaded microspheres with different release profiles into the PLGA/β-tricalcium phosphate scaffolds.

Nanofiber-mediated microRNA-126 delivery to vascular endothelial cells for blood vessel regeneration.

UNLABELLED As manipulation of gene expression by virtue of microRNAs (miRNAs) is one of the emerging strategies for cardiovascular disease remedy, local delivery of miRNAs to a specific vascular tissue is challenging. In this work, we developed an efficient delivery system composed of electrospun fibrous membranes and target carriers for the intracellular delivery of miRNA-126 (miR-126) to vascular endothelial cells (VECs) in the local specific vascular environment. A bilayer vascular scaffold was specially prepared via emulsion electrospinning of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) and dual-power electrospinning of poly(ε-caprolactone) (PCL) and gelatin. The inner layer of PELCL, which was loaded with complexes of miR-126 in REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol), regulated the response of VECs, while the outer layer of PCL/gelatin contributed to the mechanical stability. Biological activities of the miR-126-loaded electrospun membranes were evaluated by cell proliferation and SPRED-1 expression of a miR-126 target gene. By encapsulating targeting complexes of miR-126 in the electrospun membranes, a sustained release profile of miRNA was obtained for 56days. Significant down-regulation of SPRED-1 gene expression in VECs was detected on day 3, and it was found that miR-126 released from the electrospun membranes accelerated VEC proliferation in the first 9days. The bilayer vascular scaffold loaded with miR-126 complexes could also improve endothelialization in vivo. These results demonstrated the potential of this approach towards a new and more effective delivering system for local delivery of miRNAs to facilitate blood vessel regeneration. STATEMENT OF SIGNIFICANCE Tissue engineering of small-diameter blood vessels is still challenging because of thrombosis and low long-term patency. The manipulation of gene expression by miRNAs could be a novel strategy in vascular regeneration. Here, we report an efficient delivery system of electrospun fibrous scaffold combined with REDV peptide-modified trimethyl chitosan for targeted intracellular delivery of miR-126 to VECs in the local vascular environment. Results exhibited that miR-126 released from the electrospun membrane could modulate VEC proliferation via down-regulation of SPRED-1 gene expression. The electrospun scaffolds loaded with target-delivery carriers may serve as an ideal platform for local delivery of miRNAs in the vascular tissue engineering.

Preparation of PLGA Scaffolds with Graded Pores by Using a Gelatin-Microsphere Template as Porogen

Abstract Porous scaffolds with graded pores are crucial to osteochondral regeneration. In this study, a technique combining solution casting with gelatin-microsphere template leaching has been developed to produce poly(L-lactide-co-glycolide) (PLGA) scaffolds with graded pores. The traditional emulsification and solvent extraction method was improved by using the gradient ethanol/water solutions to extract water to prepare gelatin microspheres with a smooth surface without the use of any surfactant. Gelatin microspheres with different diameters were in sequence put into a custom-made cylindrical Teflon mold and bonded together to obtain gelatin-microsphere templates. By using the gelatin-microsphere templates as porogen, PLGA scaffolds with graded pore size across the cylindrical axis were prepared. The porosity of the scaffold was as high as 95%. The pore size effect on osteoblasts was studied. The results showed that the graded scaffolds possessed good biocompatibility for osteoblast growth. During the 14 days culture, the cell proliferation of all the three pore layers displayed the trend of increasing. The proliferation rate of the large pore layer was lower than the other two layers. However, the difference of alkaline phosphatase activity on the three pore layers was not statistically significant. We assumed that it was probably because of the hydrophobicity and the short culture time. It was demonstrated that gradient ethanol/water solutions provided a simple way to prepared gelatin microspheres. The graded scaffolds would provide potential application for osteochondral regeneration.

Strategies for anti-icing: low surface energy or liquid-infused?

Anti-icing is of great importance in society since icing on facility surfaces may bring about serious disasters and economical losses in fields such as aerospace, transportation and electrical communication. Development of polymeric coatings with excellent anti-icing behaviours has been one of the practical topics in recent years. Control of the chemical compositions and topological surface structures is vital to anti-icing coatings. In this review, we summarize the recent progresses on polymeric anti-icing coatings prepared from low surface energy, hydrophilic or amphiphilic polymers. Surface characteristics of the anti-icing coatings including morphology, wettability and ice adhesion strength are discussed. Comparisons between representative studies, including low surface energy coatings and liquid-infused slippery surfaces will be highlighted, with emphasis on the polymer substrate properties and innovative aspects. This review is aimed at giving a brief and crucial overview of the strategies for preparation of icephobic coatings and fulfillment of the anti-icing behaviours.

Synthesis and characterization of core–shell polyacrylate latex containing fluorine/silicone in the shell and the self-stratification film

A series of core–shell polyacrylate latexes with different fluorine/silicone monomer concentrations were prepared successfully by seeded emulsion polymerization. Dodecafluoroheptyl methacrylate and perfluorooctyl methacrylate with different fluorinated side chains were employed as fluorinated monomers, and γ-methacryloxypropyl triisopropoxidesilane (MAPTIPS) was used as a silicone-containing monomer as well as a self-cross-linking agent. The morphology and chemical structure of the latexes were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, and differential scanning calorimetry, and the self-stratification properties of the latex film were verified by X-ray photoelectron spectroscopy and static contact angle measurement. The results showed that the fluorine/silicone-containing polyacrylate latexes presented a uniformly spherical core–shell structure, and the latex films displayed a preferential distribution of fluorinated composition near the surface, which was more remarkable with the synergism effect between the fluorine monomer and MAPTIPS. Additionally, the hydrophobicity and oleophobicity of the latex films exhibited high relevance with the fluorine/silicone monomer concentrations as well as the fluorinated side-chain structure.