Development of Non‐Cell Adhesive Vascular Grafts Using Supramolecular Building Blocks

Cell‐free approaches to in situ tissue engineering require materials that are mechanically stable and are able to control cell‐adhesive behavior upon implantation. Here, the development of mechanically stable grafts with non‐cell adhesive properties via a mix‐and‐match approach using ureido‐pyrimidinone (UPy)‐modified supramolecular polymers is reported. Cell adhesion is prevented in vitro through mixing of end‐functionalized or chain‐extended UPy‐polycaprolactone (UPy‐PCL or CE‐UPy‐PCL, respectively) with end‐functionalized UPy‐poly(ethylene glycol) (UPy‐PEG) at a ratio of 90:10. Further characterization reveals intimate mixing behavior of UPy‐PCL with UPy‐PEG, but poor mechanical properties, whereas CE‐UPy‐PCL scaffolds are mechanically stable. As a proof‐of‐concept for the use of non‐cell adhesive supramolecular materials in vivo, electrospun vascular scaffolds are applied in an aortic interposition rat model, showing reduced cell infiltration in the presence of only 10% of UPy‐PEG. Together, these results provide the first steps toward advanced supramolecular biomaterials for in situ vascular tissue engineering with control over selective cell capturing.

     

Supramolecular Peptide/Polymer Hybrid Hydrogels for Biomedical Applications

Peptides and polymers are the “elite” building blocks in hydrogel fabrication where the typical approach consists of coupling specific peptide sequences (cell adhesive and/or enzymatically cleavable) to polymer chains aiming to obtain controlled cell responses (adhesion, migration, differentiation). However, the use of polymers and peptides as structural components for fabricating supramolecular hydrogels is less well established. Here, the literature on the design of peptide/polymer systems for self‐assembly into hybrid hydrogels, as either peptide‐polymer conjugates or combining both components individually, is reviewed. The properties (stiffness, mesh structure, responsiveness, and biocompatibility) of the hydrogels are then discussed from the viewpoint of their potential biomedical applications.     

Hydrophobic/hydrophilic P(VDF‐TrFE)/PHEA polymer blend membranes

Polymer blend membranes have been obtained consisting of a hydrophilic and a hydrophobic polymers distributed in co‐continuous phases. In order to obtain stable membranes in aqueous environments, the hydrophilic phase is formed by a poly(hydrohyethyl acrylate), PHEA, network while the hydrophobic phase is formed by poly(vinylidene fluoride‐co‐trifluoroethylene) P(VDF‐TrFE). To obtain the composites, in a first stage, P(VDF‐TrFE) is blended with poly(ethylene oxyde) (PEO), the latter used as sacrificial porogen. P(VDF‐TrFE)/PEO blend membranes were prepared by solvent casting at 70°C followed by cooling to room temperature. Then PEO is removed from the membrane by immersion in water obtaining a P(VDF‐TrFE) porous membrane. After removing of the PEO polymer, a P(VDF‐TrFE) membrane results in which pores are collapsed. Nevertheless the pores reopen when a mixture of hydroxethyl acrylate (HEA) monomer, ethyleneglycol dimethacrylate (as crosslinker) and ethanol (as diluent) is absorbed in the membrane and subsequent polymerization yields hybrid hydrophilic/hydrophobic membranes with controlled porosity. The membranes are thus suitable for lithium‐ion battery separator membranes and/or biostable supports for cell culture in biomedical applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 672–679     

An Improved Design and Versatile New Lamination Fabrication Method for Twin Electrode Thin Layer Cells Utilizing Track‐etch Membranes

Reported here are laminated membrane electrodes, an improved design and more advantageous method of fabrication for previously reported thin layer cell electrode systems developed on track‐etch membranes. The laminated membrane approach potentially further improves flow resistance by dramatically reducing the surface area to volume ratio, but also produces a cohesive device that can be more readily applied to a broad range of applications. In addition, this new fabrication method was implemented in a scalable, commercial process and resulting product demonstrations indicate that volume manufacturing is feasible. Characterization of laminated membrane electrodes reveal redox cycling amplification factors as high as 30 with linear responses to variable concentrations of redox couple. These performance characteristics are shown to be comparable to similar generator‐collector systems fabricated through much more laborious laboratory methods. This combination of added versatility, cost‐reduced fabrication and exceptional performance clearly reveals unrealized potential of track‐etch membrane approaches and boosts their candidacy as powerful new options for generator‐collector electrode systems.     

Adaptive Amphiphilic Dendrimer‐Based Nanoassemblies as Robust and Versatile siRNA Delivery Systems

siRNA delivery remains a major challenge in RNAi‐based therapy. Here, we report for the first time that an amphiphilic dendrimer is able to self‐assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available nonviral vectors. In addition, this amphiphilic dendrimer is able to harness the advantageous features of both polymer and lipid vectors and hence promotes effective siRNA delivery. Our study demonstrates for the first time that dendrimer‐based adaptive supramolecular assemblies represent novel and versatile means for functional siRNA delivery, heralding a new age of dendrimer‐based self‐assembled drug delivery in biomedical applications.     

Reversible Supramolecular Surface Attachment of Enzyme–Polymer Conjugates for the Design of Biocatalytic Filtration Membranes

To be used successfully in continuous reactor systems, enzymes must either be retained using filtration membranes or immobilized on a solid component of the reactor. Whereas the first approach requires large amounts of energy, the second approach is limited by the low temporal stability of enzymes under operational conditions. To circumvent these major stumbling blocks, we have developed a strategy that enables the reversible supramolecular immobilization of bioactive enzyme–polymer conjugates at the surface of filtration membranes. The polymer is produced through a reversible addition–fragmentation transfer method; it contains multiple adamantyl moieties that are used to bind the resulting conjugate at the surface of the membrane which has surface‐immobilized cyclodextrin macrocycles. This supramolecular modification is stable under operational conditions and allows for efficient biocatalysis, and can be reversed by competitive host–guest interactions.     

Preparation and characterization of asymmetric polyethersulfone (PES) membranes

Flat‐sheet asymmetric polyethersulfone (PES) membranes were prepared from polyethersulfone (PES)/ polyethylene glycol (PEG)/ N‐methyl‐2‐pyrrolidone (NMP) system via phase inversion induced by immersion precipitation in water coagulation bath. Effects of propionic acid (PA) as a non‐solvent additive (NSA) on morphology and performance of the membranes prepared from PES/PEG 6000/NMP system in water coagulation bath were investigated. The cross section morphology of the membranes was studied by scanning electron microscopy (SEM). In addition, performance of the membranes was studied by water content measurements and separation experiments using pure water and human serum albumin (HSA) protein solution as feeds. According to SEM analysis, it was found out that the NSA has a significant influence on the structure of the skin layer and the sublayer. The obtained results indicated that addition of PA to the casting solution decreases permeation flux of the prepared membranes. Copyright © 2009 John Wiley & Sons, Ltd.     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

Facile Fabrication of AIE‐Active Fluorescent Polymeric Nanoparticles with Ultra‐Low Critical Micelle Concentration Based on Ce(IV) Redox Polymerization for Biological Imaging Applications

Fluorescent polymeric nanoparticles (FPNs) with aggregation‐induced emission (AIE) property have received increasing attention and possess promising biomedical application potential in the recent years. Many efforts have been devoted to the fabrication methodologies of FPNs and significant advance has been achieved. In this contribution, a novel strategy for the fabrication of AIE‐active amphiphilic copolymers is reported for the first time based on the Ce(IV) redox polymerization. As an example, ene group containing AIE‐active dye (named as Phe‐alc) is directly grafted onto a water soluble polymer polyethylene glycol (PEG) in H₂O/THF system under low temperature. Thus‐obtained amphiphilic fluorescent polymers will self‐assemble into FPNs with ultra‐low critical micelle concentration, ultra‐brightness, and great water dispersibility. Biological evaluation results suggest that the PEG‐poly(Phe‐alc) possess excellent biocompatibility and can be used for tracing their behavior in cells using confocal laser scanning microscope. These features make PEG‐poly(Phe‐alc) FPNs promising candidates for many biomedical applications, such as cell imaging, drug delivery vehicles, and targeted tracing. More importantly, many other functional groups can also be incorporated into these AIE‐active FPNs through the redox polymerization. Therefore, the redox polymerization should be a facile and effective strategy for fabrication of AIE‐active FPNs.

     

Dual Electrospun Supramolecular Polymer Systems for Selective Cell Migration

Dual electrospinning can be used to make multifunctional scaffolds for regenerative medicine applications. Here, two supramolecular polymers with different material properties are electrospun simultaneously to create a multifibrous mesh. Bisurea (BU)‐based polycaprolactone, an elastomer providing strength to the mesh, and ureido‐pyrimidinone (UPy) modified poly(ethylene glycol) (PEG), a hydrogelator, introducing the capacity to deliver compounds upon swelling. The dual spun scaffolds are modularly tuned by mixing UPyPEG hydrogelators with different polymer lengths, to control swelling of the hydrogel fiber, while maintaining the mechanical properties of the scaffold. Stromal cell derived factor 1 alpha (SDF1α) peptides are embedded in the UPyPEG fibers. The swelling and erosion of UPyPEG increase void spaces and released the SDF1α peptide. The functionalized scaffolds demonstrate preferential lymphocyte recruitment proposed to be created by a gradient formed by the released SDF1α peptide. This delivery approach offers the potential to develop multifibrous scaffolds with various functions.     

Photo‐Driven Ion Transport for a Photodetector Based on an Asymmetric Carbon Nitride Nanotube Membrane

Conventional photosensing devices work mainly by electron processing and transport, while visual systems in intelligence work by integrative ion/electron signals. To realize smarter photodetectors, some photoionic device or the combination of ionic and electronic devices are necessary. Now, an ion‐transport‐based self‐powered photodetector is presented based on an asymmetric carbon nitride nanotube membrane, which can realize fast, selective, and stable light detection while being self‐powered. Local charges are continuously generated at the irradiated side of the membrane, and none (fewer) at the non‐irradiated side. The resulting surface charge gradient in carbon nitride nanotube will drive ion transport in the cavity, thus realizing the function of ionic photodetector. With advantages of low cost and easy fabrication process, the concept of ionic photodetectors based on carbon nitride anticipates wide applications for semiconductor biointerfaces.     

Steric Constraints Induced Frustrated Growth of Supramolecular Nanorods in Water

A unique example of supramolecular polymerisation in water based on monomers with nanomolar affinities, which yield rod‐like materials with extraordinarily high thermodynamic stability, yet of finite length, is reported. A small library of charge‐neutral dendritic peptide amphiphiles was prepared, with a branched nonaphenylalanine‐based core that was conjugated to hydrophilic dendrons of variable steric demand. Below a critical size of the dendron, the monomers assemble into nanorod‐like polymers, whereas for larger dendritic side chains frustrated growth into near isotropic particles is observed. The supramolecular morphologies observed by electron microscopy, X‐ray scattering and diffusion NMR spectroscopy studies are in agreement with the mechanistic insights obtained from fitting polymerisation profiles: non‐cooperative isodesmic growth leads to degrees of polymerisation that match the experimentally determined nanorod contour lengths of close to 70 nm. The reported designs for aqueous self‐assembly into well‐defined anisotropic particles has promising potential for biomedical applications and the development of functional supramolecular biomaterials, with emerging evidence that anisotropic shapes in carrier design outperform conventional isotropic materials for targeted imaging and therapy.     

ZrO2纳米粒子原位杂化PVDF膜的制备及其抗污染性能

针对传统聚合物膜抗污染性差的问题,本文从杂化膜结构设计出发,提出将ZrO2纳米粒子的原位制备和聚偏氟乙烯(PVDF)相转化成膜过程有机结合的制膜新方法.该方法将阴离子交换树脂引入到N,N-二甲基甲酰胺(DMF)中,以氧氯化锆为原料,利用阴离子交换树脂提供的―OH与无机盐的阴离子进行交换,得到ZrO2纳米粒子均匀分散的N,N-二甲基甲酰胺溶胶体系.随后将PVDF聚合物溶解到所得的N,N-二甲基甲酰胺溶胶体系中,获得均一、透明的铸膜液.利用X射线光电子能谱(XPS)和透射电子显微镜(TEM)对杂化膜中锆的存在状态和分散性能进行了表征.结果表明,ZrO2纳米粒子均匀分散在PVDF基体中,并且形成的纳米粒子的粒径约为10-20 nm.通过粘度、分相速度和膜形态的测定,研究了成膜机理.结果表明,ZrO2纳米粒子的引入加速了铸膜液成膜过程的分相速度.杂化膜的亲水性能通过接触角测定仪进行了评价.并选择以牛血清蛋白为代表模拟污染物,考察了杂化超滤膜的抗污染性能.结果表明,原位形成的ZrO2纳米粒子显著提高了膜的亲水性,减少了膜对蛋白质的吸附.这种将ZrO2纳米粒子的原位制备和PVDF相转化成膜过程有机结合的制膜新方法在有机-无机杂化膜的制备领域具有显著意义.     

Novel nanocomposite membranes from cellulose acetate and clay‐silica nanowires

In this study, a new class of heterogeneous membranes based on cellulose acetate (CA) polymer and a complex filler clay‐silica nanowires (SiO₂NWs) was investigated for potential biomedical applications. SiO₂NWs were synthesized using natural clay through a facile sol–gel method and were dispersed in the polymer solution by sonication in the 1.25, 2.5, and 5% weight ratio to the CA acetate polymer. Membranes were subsequently prepared via phase inversion by precipitation of the CA polymer in water. The pristine CA membrane and SiO₂NWs based nanocomposites membranes were characterized using different characterization techniques. The presence of the SiO₂NWs in the CA membrane was found to significantly enhance the protein retention, water wettability and thermal as well as mechanical properties in comparison to the pristine CA membrane. Water flows studies at different temperatures and the retention of bovine serum albumin have been studied and the nanocomposite membranes were found to exhibit superior performances compared with the pristine CA membranes. SiO₂NWs‐CA membranes showed a much higher stability to the water temperature change during separation than CA membranes. Morphological changes clearly revealed that the composite membrane were much more compact than the pristine CA membranes. The rabbit dermal fibroblasts cell viability in cultures after 72 hr of incubation was found to be greater than 80%. These newly synthesized composite membranes exhibit a high potential to be used for various medical applications because of their non‐cytotoxic characteristics. Copyright © 2016 John Wiley & Sons, Ltd.     

Self‐Healing Polyester Urethane Supramolecular Elastomers Reinforced with Cellulose Nanocrystals for Biomedical Applications

Stretchable self‐healing urethane‐based biomaterials have always been crucial for biomedical applications; however, the strength is the main constraint of utilization of these healable materials. Here, a series of novel, healable, elastomeric, supramolecular polyester urethane nanocomposites of poly(1,8‐octanediol citrate) and hexamethylene diisocyanate reinforced with cellulose nanocrystals (CNCs) are introduced. Nanocomposites with various amounts of CNCs from 10 to 50 wt% are prepared using solvent casting technique followed by the evaluation of their microstructural features, mechanical properties, healability, and biocompatibility. The synthesized nanocomposites indicate significantly higher tensile modulus (approximately 36–500‐fold) in comparison to the supramolecular polymer alone. Upon exposure to heat, the materials can reheal, but nevertheless when the amount of CNC is greater than 10 wt%, the self‐healing ability of nanocomposites is deteriorated. These materials are capable of rebonding ruptured parts and fully restoring their mechanical properties. In vitro cytotoxicity test of the nanocomposites using human dermal fibroblasts confirms their good cytocompatibility. The optimized structure, self‐healing attributes, and noncytotoxicity make these nanocomposites highly promising for tissue engineering and other biomedical applications.     

Structural Versatility in Slide‐Ring Gels: Influence of Co‐Threaded Cyclodextrin Spacers

We describe a one‐pot strategy for the fabrication of novel slide‐ring (SR) gels based on supramolecular polyrotaxane structures with cyclodextrin‐derived cross‐links and additional free cyclodextrin ring spacers co‐threaded onto the polymer backbones. Photoinitiated thiol‐yne click coupling leads to facile hydrogel fabrication from pseudo‐polyrotaxanes prepared in situ from β‐cyclodextrin derivatives and bifunctional polyethylene glycol (PEG). The obtained SR gels were characterized by NMR spectroscopy using a polyrotaxane model compound with the ratio of cyclodextrin sliding spacers to PEG backbone controlled by adjusting the feed ratio of the starting materials. This structural tuning leads to dramatic changes in the rheological properties, mechanical properties, and swelling behavior of the SR gels. In addition, the coupling of simple synthetic procedures with enhanced properties offers a versatile approach to novel elastomeric materials. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 55, 1156–1165     

Renal Epithelial Monolayer Formation on Monomeric and Polymeric Catechol Functionalized Supramolecular Biomaterials

Induction of a functional, tight monolayer of renal epithelial cells on a synthetic membrane to be applied in a bioartificial kidney device requires for bio‐activation of the membrane. The current golden standard in bio‐activation is the combination of a random polymeric catechol (L‐DOPA) coating and collagen type IV (Col IV). Here the possibility of replacing this with defined monomeric catechol functionalization on a biomaterial surface using supramolecular ureido‐pyrimidinone (UPy)‐moieties is investigated. Monomeric catechols modified with a UPy‐unit are successfully incorporated and presented in supramolecular UPy‐polymer films and membranes. Unfortunately, these UPy‐catechols are unable to improve epithelial cell monolayer formation over time, solely or in combination with Col IV. L‐DOPA combined with Col IV is able to induce a tight monolayer capable of transport on electrospun supramolecular UPy‐membranes. This study shows that a random polymeric catechol coating cannot be simply mimicked by defined monomeric catechols as supramolecular additives. There is still a long way to go in order to synthetically mimic simple natural structures.     

Mimicking the cell membrane with block copolymer membranes

Cell membranes are essential barriers in Nature. To understand their properties and functions and to develop desirable applications, a simple and elegant approach is to study membranes that mimic the cell membrane. Lipid bilayers represent simple models that are physiologically representative when in the form of mixtures of various lipids, but they are not adequately stable even when covered with amphipathic proteins or when combined with polymers, thus preventing technological applications. This makes necessary the design of completely synthetic membranes. In this respect, amphiphilic copolymers that self‐assemble under dilute aqueous conditions and generate supramolecular polymer vesicles or films are ideal candidates for synthetic membranes. Their versatility in terms of chemistry and properties (permeability, mechanical stability, thickness), if appropriately designed, enable the insertion of biological molecules, such as membrane proteins and biopores, or the attachment of biomolecules at their surfaces. Here, we present the domain of synthetic membranes based on amphiphilic copolymers beginning with their generation and up to their applications in medicine, the food industry, and technology. Even though significant progress has been made in combining them with membrane proteins, open questions remain with respect to desired properties that could accommodate biological molecules and support further development of the field, from both the point of view of fundamental understanding and of applications. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

FET‐Based Chemical Sensor Systems Fabricated with Standard Technologies

Miniaturized solid‐state ion sensors based on field‐effect transistors on silicon can take advantage of the capabilities of microelectronics and microsystems technology for the integration of combined functionalities. Optimized solid‐state chemical sensors usually require specific materials and fabrication processes. However, if standard fabrication processes can be used, integrated chemical sensor systems can be developed in a shorter time and in a cost effective way. We show that, for applications in which a long operating time is not required, such as in disposable biomedical sensors, good integrated sensor systems can be fabricated with standard materials and processes. Specific examples are presented, such as multisensor systems, sensors with integrated signal‐processing circuits and sensors with particle manipulation electrodes.