A continuous electrospinning technique was applied to fabricate double layer tubular tissue engineering vascular graft (TEVG) scaffold. The luminal layer was made from poly(ɛ-caprolac-tone)(PCL) ultrafine fibers via common single axial electrospinning followed by the outer layer of core-shell structured nanofibers via coaxial electrospinning. For preparing the outer layernano-fibers, the PCL was electrospun into the shell and both bovine serum albumin (BSA) and tetrapeptide val-gal-pro-gly (VAPG) were encapsulated into the core. The core-shell structure in the outer layer fibers was observed by transmission electron microscope (TEM). The in vitro release tests exhibited the sustainable release behavior of BSA and VAPG so that they provided a better cell growth environment in the interior of tubular scaffold wall. The in vitro culture of smooth muscle cells (SMCs) demonstrated their potential to penetrate into the scaffold wall for the 3D cell culture. Subsequently, 3D cell coculture was conducted. First, SMCs were seeded on the luminal surface of the scaffold and cultured for 5 days, and then endothelial cells (ECs) were also seeded on the luminal surface and cocultured with SMCs for another 2 days. After stained with antibodies, 3D cell distribution on the scaffold was revealed by confocal laser scanning microscopy (CLSM) where ECs were mainly located on the luminal surface whereas SMCs penetrated into the surface and distributed inside the scaffold wall. This double layer tubular scaffold with 3D cell distribution showed the promise to develop it into a novel TEVG for clinical trials in the near future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3863–3871, 2015.

PCL-heparin conjugates were synthesized by coupling mono-hydroxyl terminated PCL (M_n = 2000-10000 g/mol) with heparin via EDC/NHS chemistry. The conjugates enabled to self-assemble into the core-shell nanoparticles in around 100 nm diameter to load binary anti-cancer drugs. Lipophilic and neutral paclitaxel (PTX) was first encapsulated in the core, and then hydrophilic and positive charged doxorubicin (DOX) was incorporated into the negative charged shell of PTX loaded nanoparticles via the electrostatic interaction. The in vitro release profiles of the binary-drug loaded nanoparticles revealed that both PTX and DOX were sustainably released from the particles but behaved differently. The release of DOX was pH dependent, ensuring more drug to be released in the tumor cells than in the normal ones. Hence these particles were featured by a sequential controlled drug delivery behavior with a significant cytotoxicity to cervical cancer (Hela cell) and breast cancer (MDA-MB-321) cells. The CLSM observations clearly indicated that both loaded PTX and DOX aggregated in the nucleus of tumor cells to exert their anti-tumor pharmacodynamic effect on the cells. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 880–889, 2014.

Biodegradable polyrotaxane-based triblock copolymers were synthesized via the bulk atom transfer radical polymerization (ATRP) of n-butyl methacrylate (BMA) initiated with polypseudo-rotaxanes (PPRs) built from a distal 2-bromoisobutyryl end-capped poly(ε-caprolactone) (Br-PCL-Br) with α-cyclodextrins (α-CDs) in the presence of Cu(I)Br/N,N,N′,N″,N″-pentamethyldiethylenetriamine at 45 ºC. The structure was characterized in detail by means of ¹H NMR, gel permeation chromatography, wide-angle X-ray diffraction, DSC and TGA. When the feed molar ratio of BMA to Br-PCL-Br was changed from 128 to 300, the degree of polymerization of PBMA blocks attached to two ends of the PPRs was in the range 382 − 803. Although about a tenth of the added α-CDs were still threaded onto the PCL chain after the ATRP process, the movable α-CDs made a marked contribution to the mechanical strength enhancement, blood anticoagulation activity and protein adsorption repellency of the resulting copolymers. Meanwhile, they could also protect the copolymers from the attack of H₂O and Lipase AK Amano molecules, exhibiting a lower mass loss as evidenced in hydrolytic and enzymatic degradation experiments. © 2013 Society of Chemical Industry

A polypseudorotaxane (PPR) comprising γ-cyclodextrin (γ-CD) as host molecules and poly(N-isopropylacrylamide) (PNIPAM) as a guest polymer is prepared via self-assembly in aqueous solution. Due to the bulky pendant isopropylamide group, PNIPAM exhibits size-selectivity toward self-assembly with α-, β-, and γ-CDs. It can fit into the cavity of γ-CD to give rise to a PPR, but cannot pass through α-CD and β-CD under the same conditions. The ratio of the number of γ-CD molecules to entrapped NIPAM repeat units is kept at 1:2.2 or 1:2.4, determined by ¹H NMR spectroscopy and TGA analysis, respectively, indicating that there are more than 2 but less than 3 NIPAM repeat units included by one γ-CD molecule. This finding opens new avenues to PPR-based supramolecular polymers to be used as solid, stimuli-responsive materials.

Poly(ε-caprolactone) (PCL) was conjugated with heparin and fabricated into nonwoven tubular scaffold by electrospinning. The dynamic contact angle analysis revealed the hydrophilicity improvement due to heparin concentrating on the conjugate surface. The microbicinchoninic acid and quartz crystal microbalance measurements implied that the conjugate can significantly reduce the absorption of plasma protein, such as albumin and fibrinogen, indicative of the good blood biocompatibility. As evidenced by Enzyme Linked Immunosorbent Assay, the electrospun conjugate scaffolds possessed a higher loading capability of vascular endothelial growth factor (VEGF) than that of the blank PCL in aqueous solution via static interaction. The viability of loaded VEGF was evaluated by cell culture and adhesion tests. The amount and morphology of cells were substantially improved after VEGF was loaded into scaffolds exhibiting excellent cell biocompatibility. To assess the in vivo biocompatibility, a tubular scaffold (L = 4 cm, D = 2 mm) was transplanted into dog's femoral artery. The scaffold patency was inspected by carotid artery angiography 4 weeks after implantation. The explanted scaffold was also investigated by histological analysis including hematoxyline eosin, Millere Masson (collagen and elastin), and von Kossa (calcium) stain. Furthermore, von Willebrand factor immunohistochemical stain was performed to examine the formation of endothelial layer. The conjugate shows the potential to be used as scaffold materials in vascular tissue engineering. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:3251–3258, 2012.

In this study polyrotaxane (PR)-based triblock copolymers were first synthesized via the atom transfer radical polymerization (ATRP) of N-isopropylacrylamide initiated with the self-assembly of a distal 2-bromoisobutyryl end-capped Pluronic 17R4 with a varying amount of α-cyclodextrins (α-CDs) in the presence of CuCl/PMDETA at 25°C in aqueous solution. The α-CDs entrapped on the copolymer chain were then linked with hexamethylene diisocyanate to give rise to novel slightly cross-linked polyrotaxanes (SCPRs) in DMF at 45°C. The structures of the PR-based triblock copolymers and SCPRs were characterized by ¹H NMR, ¹³C CP/MAS, GPC and TGA analyses. The number-average molecular weight of the resulting SCPRs was nearly three and five times of their precursor after linking with a low polydispersity index range of 1.08–1.28. The thermo-responsive transition of both PR-based supramolecular polymers in aqueous solution was demonstrated by turbidity measurements and the self-aggregated morphologies were also evidenced by TEM observations.

When γ-CDs are added to an aqueous solution of PNIPAAm-b-PEG-b-PNIPAAm block copolymer, they are threaded onto the polymer chains to give loose-fit polypseudorotaxanes (PPRs). The inclusion complexation shows a marked dependence on the length of the PNIPAAm blocks although the threaded γ-CDs are preferably located on the central PEG block. The structure of the resulting PPRs is characterized by using XRD, ¹H and ¹³C CP/MAS NMR, TGA FTIR, and DSC analyses. Because of the mismatched fit between the guest polymer chain and the cavity of the host γ-CDs, these PPRs may be promising in applications as solid stimuli-responsive materials.

A series of biodegradable polyurethanes (PUs) were synthesized using poly(ε-caprolactone) diol (PCL) to react with L-lysine ethyl ester diisocyanate (LDI) chain extend with L-lysine ethyl ester (LEE) in solution of DMF. The structure was characterized by gel permeation chromatography, ¹H-NMR, Fourier transform infrared, and DSC analyses. Mechanical property testing showed that their tensile strength rose with increasing the hard segment content with a maximum tensile strength of 34.43 ± 1.73 MPa. The average mass loss for the hydrolytic degradation was only about 13 % in 56 days while this value for the enzymatic degradation was around 95 % in 30 days. The morphological and biomechanical characters of the tubular scaffolds electrospun from the as-prepared PUs were also examined. As the solution concentration was varied from 10 to 18% (w/v), the fiber diameter was progressively increased, and the scaffold tensile strength was enhanced from 2.82 ± 0.16 MPa to 7.07 ± 0.44 MPa, the suture retention strength from 2.48 ± 0.33 to 8.38 ± 0.35 N, and the burst pressure strength from 72 ± 2 to 172 ± 2 kPa, all higher than those of native blood vessels. At the same time, the L-929 mouse fibroblasts (L-929) and human umbilical vein endothelial cells were used in cytotoxicity and cell-adhesion evaluations toward the electrospun scaffolds. The level of toxicity is less than level 1, and cells were found to attach well to and remain viable on the scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.

The unexpected formation of polypseudorotaxanes via attaching 2-bromoisobutyryl groups to both ends of poly(ethylene glycol) (PEG), which leads to the self-assembly with γ-cyclodextrins in aqueous solution, is reported in this study. The resulting polypseudorotaxanes exhibit stable and unconventional single PEG bent conformations as evident from XRD, FTIR, GPC, ¹³C CP/MAS, and ¹H NMR analyses. These polypseudorotaxane products are so stable that they can initiate the bulk ATRP of butyl methacrylate to give rise to the same conformational polypseudorotaxanes.

Owing to a large cavity, γ-cyclodextrin (γ-CD) can form double-chain inclusion complexes with linear polymeric chains such as poly(ethylene glycol) (PEG) and poly(ε-caprolactone). However, to date few reports have focused on the end-capping of these kinds of fascinating supramolecular entities. In this study, atom transfer radical polymerization (ATRP) was employed to prepare double-chain stranded polyrotaxanes (PRs) with lengthily tunable poly(2-hydroxyethyl methacrylate) (PHEMA) blocks as bulky end-cappers. ATRP of HEMA was carried out using pseudopolyrotaxanes (PPRs) self-assembled from a distal 2-bromoisobutyryl end-capped PEG (BriB-PEG-iBBr) with varying amounts of γ-CDs as macroinitiator in the presence of Cu(I)Br/N,N,N′,N″,N″-pentamethyldiethylenetriamine in aqueous solution at room temperature. The resulting PRs were demonstrated by the unique H-like double-chain stranded supramolecular architecture end-capped with lengthily tunable PHEMA blocks. When the feed molar ratio of γ-CD:BriB-PEG-iBBr varied from 5 to 60 in PPRs, the feed molar ratio in PRs was found to remain at around 20 with a higher yield. ATRP was successfully applied to prepare double-chain stranded PRs end-capped with lengthily tunable PHEMA blocks. This provides a protocol for the preparation of novel H-like PR-based block copolymers. Copyright © 2010 Society of Chemical Industry

A silicone-containing polymer was synthesized by addition polymerization between 1,12-bis(3-methyl-3-oxetanyl)-2,5,8,11-tetraoxadodecane and dichloride dimethylsilane catalyzed by tetrabutylammonium bromide and was characterized by Fourier transform infrared spectroscopy, ¹H-NMR, gel permeation chromatography, and differential scanning calorimetry analyses. To manufacture a tough solid electrolyte membrane, various amounts of a poly(vinylidene fluoride-co-hexafluoropropene) copolymer was used to reinforce this silicone-containing polymer. The mechanical properties and compatibility of the resulting membranes were assessed by mechanical testing and scanning electron microscopy observation. The ionic conductivity was assayed from an alternating-current impedance spectrum. The results reveal that the maximum ionic conductivity reached 7.4 × 10⁻⁵ S/cm at 30°C and 2.6 × 10⁻⁴ S/cm at 80°C, respectively. Additionally, the linear sweep voltammetry tests showed that this kind of the blended polymer electrolyte was electrochemical stable until 4.3 V. The thermogravimetric analysis measurements also implied its good thermal stability. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Two novel polyethers, one comb-like and another hyperbranched, were synthesized by the cationic ring-opening polymerization of 3-(methoxy(triethylenoxy))methyl- and 3-(hydroxy-(triethylenoxy))methyl-3′-methyloxetane, respectively. The former reacted with a multifunctional isocyanate and the latter with a difunctional isocyanate to give rise to the corresponding crosslinked poly(ether urethane) elastomers, PCEU and PHEU. Accordingly, two kinds of solid polymer electrolytes (SPEs) were prepared from these two elastomers in situ in the presence of lithium salt trifluoromethanesulfonimide. It was found that the PCEU-based SPEs shows a higher ionic conductivity than that PHEU-based ones due to its more mobile pendent chains and appropriate crosslinking density in the polymeric network. The maximum ionic conductivities of 1.4 × 10⁻⁵ S/cm at 30°C and 3.5 × 10⁻⁴ S/cm at 80°C were attained at the molar ratio of O/Li = 7.5. The DSC measurements clearly demonstrated that PCEU indeed possesses the more flexible chain motion ability than PHEU. The electrochemical stability window of PCEU, which is 1.7–4.0 V was measured by cyclic voltammogram. Additionally, the significantly high decomposition temperature as evidenced by TGA analyses endowed these SPEs a good safe performance. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

A kind of novel soft amphiphilic ABA triblock copolymers, poly(L-lysine)-b-poly(tetrahydrofuran)-b-poly(L-lysine), was synthesized by the anionic ring-opening polymerization of ε-benzyloxycarbonyl-L-lysine N-carboxyanhydride using amine-terminated poly(tetrahydrofuran) as a macroinitiator and subsequent removal of the protecting group. The resulting copolymers possessing a nearly symmetrical and narrow molecular weight distribution were dissolved in water at an appropriate concentration range at room temperature to yield vesicles as confirmed by using negative stain TEM and DLS. Meanwhile, nanotubes were obtained as the result of the conjunction of vesicles by reducing the medium temperature as evidenced by TEM. The effect of pH and salt concentration variations on the self-assembly behavior was also examined. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1042–1050, 2008